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DEFINITIONS
Trial Review
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Trial registered on ANZCTR
Registration number
ACTRN12623000798662
Ethics application status
Approved
Date submitted
4/05/2023
Date registered
26/07/2023
Date last updated
26/07/2023
Date data sharing statement initially provided
26/07/2023
Type of registration
Prospectively registered
Titles & IDs
Public title
A First-in-Human, Open-label, Phase 1/2 Study of BOS-342 in Patients with Hepatocellular Carcinoma (HCC) and other Glypican 3 (GPC3)-expressing Tumors
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Scientific title
A Phase 1/2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of BOS-342 in Patients with Hepatocellular Carcinoma (HCC) and other GPC3-expressing Tumors
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Secondary ID [1]
309314
0
Nil Known
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Universal Trial Number (UTN)
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Trial acronym
HCC
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma (HCC)
329505
0
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Other GPC3-expressing Tumors
330453
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Condition category
Condition code
Cancer
326439
326439
0
0
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Liver
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
BOS-342 (formerly known as PRS-342 and MPAL1073) is a monoclonal antibody (mAb)-like bispecific protein targeting the tumor antigen Glypican 3 (GPC3) and the costimulatory immunoreceptor 4-1BB (CD137). The anticipated mode of action of BOS-342 is to combine GPC3 binding in the tumor microenvironment with 4-1BB-induced T cell co-stimulation and expansion, leading to a higher local T cell activation and a reduced risk of systemic toxicity compared to monospecific 4-1BB targeting.
BOS-342 will be administered intravenously (IV) every 2 weeks (Q2W) until radiologically documented progressive disease (PD), unacceptable toxicity, or occurrence of any criterion for withdrawal from the study or the study treatment.
The study is comprised of 2 phases. Phase 1 is to assess the safety of BOS-342 and determine the maximum tolerated dose and/or recommended Phase 2 dose of BOS-342. Phase 2 is to evaluate the response rate in patients treated with BOS-342.
- Phase 1 (dose escalation): Small groups of participants will be enrolled one at a time. The next group will receive a higher dose of BOS-342 bi-weekly if the previous group tolerated a lower dose. These groups will be enrolled until the highest tolerated dose of BOS-342 is identified. Additional participants may be enrolled in previously cleared dose levels while some participants may be treated at higher dose levels.
- Phase 2 (dose expansion): Larger group of participants will be enrolled into the dose group selected from Phase 1. This group will receive a dose level and schedule that is deemed safe and tolerable as determined in Phase 1. Phase 2 is for collecting more information about the selected dose.
A single treatment cycle is 28 days long, with BOS-342 administered intravenously (IV) on Day 1 and Day 15 of each cycle. The starting dose of BOS-342 (Dose Level 1) is 0.5 mg/kg intravenously (IV) every two weeks (Q2W). Dose escalation decisions will be based on the safety review of data collected in Cycle 1 (dose-limiting toxicity [DLT] period). Six Doses (intravenously, every two weeks) are planned to be assessed for Phase 1: (Dose Level 1) is 0.5 mg/kg, (Dose Level 2) is 1.5 mg/kg, (Dose Level 3) is 4.5 mg/kg, (Dose Level 4) is 9 mg/kg, (Dose Level 5) is 18 mg/kg and (Dose Level 6) is 27 mg/kg.
Once the DLT period is met (28 days), the next patient will begin screening after safety data is received and Safety Review Team (SRT) meeting is completed.
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Intervention code [1]
325750
0
Treatment: Drugs
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Comparator / control treatment
NA
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Control group
Uncontrolled
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Outcomes
Primary outcome [1]
334283
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Phase 1 - To assess the safety of BOS-342 and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BOS-342
• Occurrence of dose-limiting toxicities (DLTs) .
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs.
• Incidence and shifts of clinically significant clinical laboratory abnormalities.
• Change from baseline in other observations related to safety, including electrocardiograms (ECGs), vital signs, and Karnofsky performance status.
The parameters assessed for safety endpoints include:
- Adverse events - Incidence, severity and relationship of Adverse Events/Serious Adverse Events (including withdrawals due to AEs). AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE) V5.0 dated 27Nov2017.
- Vital signs- Blood pressure will be measured using sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) will be measured using vital sign machine and respiratory rate using pulse oximetry.
- ECG- A single standard 12-lead electrocardiogram (ECG) will be recorded after the patient has been resting for at least 5 minutes in the supine position and before any blood sample collection required at the same timepoint, as specified in the Schedule of Activities (SoA) using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
- Echocardiogram - Ejection fraction is to be determined by echocardiogram, MUGA or cardiovascular MRI during Screening.
- Clinical laboratory tests - (Blood – including Hematology, Chemistry, Coagulation, Serology and Urine analysis)
- Karnofsky Performance- will be assessed by the treating investigator.
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Assessment method [1]
334283
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Timepoint [1]
334283
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Phase 1:
• Occurrence of dose-limiting toxicities (DLTs) - assessed at all scheduled visits post dosing.
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs - assessed at all visits post dosing.
• Incidence and shifts of clinically significant clinical laboratory abnormalities - reviewed at all scheduled visits.
• Change from baseline in other observations related to safety, including electrocardiograms (ECGs), vital signs, and Karnofsky performance status - ECG reviewed at C1D1 and at C2D1, Vitals and Karnofsky performance status at all visits.
The timepoints include:
- Adverse events (AEs) - AEs assessment will be performed at each visit throughout the study period from Screening through to 30 Days after last infusion of study drug (Follow Up/End of Treatment (EOT) Visit).
- Vital Signs - Vital Signs are performed during Screening, Cycle 1- Days 1, 8, 15 and 22 and all other cycles on Days 1 and 15, EoT and safety follow up. Vital signs will be measured in a supine position after 5 minutes rest and should be assessed predose (within 15 minutes of infusion), and then every 15 minutes from the start of infusion continuing through the duration of the infusion. If vital signs are not stable after completion of the infusion, vitals will be monitored every 15 minutes until stable on 2 consecutive repeated measurements. Otherwise, subsequent vital signs will be taken every 60 minutes until 4 hours following completion of the infusion. If there are no clinically significant changes in vital signs during the first 2 infusions then the vital signs schedule for subsequent infusions will be predose, every 15 minutes during the infusion, and then 1 hour from completion of infusion.
- ECG- Electrocardiograms will be performed on Cycle 1 Day 1 and Cycle 2 Day 1 predose and within 15 minutes following the end of infusion and as clinically indicated. Whenever ECG and blood / PK samples are specified to be collected at the same time, ECG will be obtained before the blood / PK sampling.
- Laboratory tests- Haematology and chemistry tests will be performed pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of each subsequent cycle, and at the EOT visit and follow up visit..
Urinalysis should be obtained pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT and safety follow up visit. Coagulation samples will be obtained pre-infusion at Screening and at Day 1 of Cycle 2.
- Karnofsky performance status for any change in symptom burden – Karnofsky Scale of PS will be assessed at Screening, Cycle 1: Days 1, 8, 15 and 22 and all other cycles on days 1 and 15 (day of drug administration), EoT and safety follow up and as clinically indicated.
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Primary outcome [2]
334289
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Phase 2 - To evaluate the response rate in patients treated with BOS-342
• Confirmed Objective response rate (ORR) per RECIST 1.1
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Assessment method [2]
334289
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Timepoint [2]
334289
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Phase 2: Response rate is evaluated every 8 weeks and at EOT.
Response rate is evaluated every 8 weeks until the subject comes off the treatment and at EOT. Imaging assessments - CT or MRI scans conducted at Screening and every 8 weeks until the subject comes off the treatment and at EoT. In the absence of disease progression, tumour assessments should continue regardless of whether participants discontinue study treatment, unless the participant starts new anti-cancer treatment, dies, withdraws consent, or the study is terminated by the Sponsor, whichever occurs first.
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Primary outcome [3]
334290
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Phase 2 - To evaluate the safety and tolerability of BOS-342
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs
• Incidence and shifts of clinically significant clinical laboratory abnormalities
• Change from baseline in other observations related to safety, including ECGs, vital signs, and Karnofsky performance status
The parameters assessed for safety endpoints include:
- Adverse events - Incidence, severity and relationship of Adverse Events/Serious Adverse Events (including withdrawals due to AEs). AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE) V5.0 dated 27Nov2017.
- Vital signs- Blood pressure will be measured using sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) is measured using vital sign machine and respiratory rate is measured using pulse oximetry.
- ECG- A single standard 12-lead electrocardiogram (ECG) will be recorded after the patient has been resting for at least 5 minutes in the supine position and before any blood sample collection required at the same timepoint, as specified in the Schedule of Activities (SoA) using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
- Echocardiogram - Ejection fraction is to be determined by echocardiogram, MUGA or cardiovascular MRI during Screening.
- Clinical laboratory tests - (Blood – including Hematology, Chemistry, Coagulation, Serology and Urine analysis)
- Karnofksy Performance- will be assessed by the treating investigator.
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Assessment method [3]
334290
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Timepoint [3]
334290
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Phase 2:
• Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and Grade 3 or higher TEAEs- Evaluated at each scheduled visit.
• Incidence and shifts of clinically significant clinical laboratory abnormalities - evaluated at each scheduled visit.
• Change from baseline in other observations related to safety, including ECGs, vital signs, and Karnofsky performance status- ECG reviewed at C1D1 and at C2D1, Vitals and Karnofsky performance status at all visits.
The timepoints include:
- Adverse events (AEs) - AEs assessment will be performed at each visit throughout the study period from Screening through to 30 Days after last infusion of study drug (Follow Up/End of Treatment (EOT) Visit).
*- Vital Signs - Vital Signs are performed during Screening, Cycle 1- Days 1, 8, 15 and 22 and all other cycles on days 1 and 15, EoT and safety follow up. Vital signs will be measured in a supine position after 5 minutes rest and should be assessed predose (within 15 minutes of infusion), and then every 15 minutes from the start of infusion continuing through the duration of the infusion. If vital signs are not stable after completion of the infusion, vitals will be monitored every 15 minutes until stable on 2 consecutive repeated measurements. Otherwise, subsequent vital signs will be taken every 60 minutes until 4 hours following completion of the infusion. If there are no clinically significant changes in vital signs during the first 2 infusions then the vital signs schedule for subsequent infusions will be predose, every 15 minutes during the infusion, and then 1 hour from completion of infusion.
- ECG- Electrocardiograms will be performed on Cycle 1 Day 1 and Cycle 2 Day 1 predose and within 15 minutes following the end of infusion and as clinically indicated. Whenever ECG and blood / PK samples are specified to be collected at the same time, ECG will be obtained before the blood / PK sampling.
- Laboratory tests- Haematology and chemistry tests will be performed pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of each subsequent cycle, and at the EOT visit and follow up visit.
Urinalysis should be obtained pre-infusion at Screening, Days 1, 8, 15 and 22 of Cycle 1, Day 1 of each subsequent cycle, and at the EOT and safety follow up visit. Coagulation samples will be obtained pre-infusion at Screening and at Day 1 of Cycle 2.
- Karnofsky performance status for any change in symptom burden – Karnofsky Scale of PS will be assessed at Screening, Cycle 1: Days 1, 8, 15 and 22 and all other cycles on days 1 and 15 (day of drug administration), EoT and safety follow up and as clinically indicated.
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Secondary outcome [1]
420118
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Phase 1 - To assess the serum PK profile of BOS-342
PK parameters for BOS-342 such as, but not limited to, maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), and area under the serum concentration versus time curve from time 0 to t (AUC0–t)
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Assessment method [1]
420118
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Timepoint [1]
420118
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Phase 1: PK parameters for BOS-342 such as, but not limited to, maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), and area under the serum concentration versus time curve from time 0 to t (AUC0–t)- evaluated by collecting PK samples as Pre-dose (samples collected at C1D1; C2D15: C3D1; C4D1; C5D1) and post dose samples collected at C1 and C2 at variable timepoints.
Samples for pharmacokinetics and bioanalytical assessment will be collected as per the PK and bioanalytical blood sample collection schedule at all scheduled cycle visits on Cycle 1 Day 1- less than 1 hour prior to drug infusion,, post-dose at 1, 2, 4, 7, 24 hours and on days 2 (24h post End of Infusion (EOI), 3 (48h post EOI), 4 (72h post EOI), 8 (168h post EOI) and 15 (336h post EOI). Cycle 2 Day 15- less than 1 hour prior to drug infusion , post-dose at 1, 2, 4, 7, 24h and on days 16 (24h post EOI), 17 (48h post EOI), 18 (72h post EOI) and 22 (168h post EOI). Cycle 3, Day 1 and subsequent cycles up to Cycle 5 – less than 1 hour Pre-dose. Schedule may be altered on the basis of evolving data.
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Secondary outcome [2]
420147
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Duration of Response (DOR) per RECIST 1.1
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Assessment method [2]
420147
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Timepoint [2]
420147
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Phase 2:
• DOR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [3]
420148
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Phase 2 - To assess the serum PK profile of BOS-342
• PK parameters for BOS-342 such as, but not limited to, Cmax, Tmax, and AUC0–t
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Assessment method [3]
420148
0
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Timepoint [3]
420148
0
Phase 2:
• PK parameters for BOS-342 such as, but not limited to, Cmax, Tmax, and AUC0–t - evaluated by collecting PK samples as Pre-dose (samples collected at C1D1; C2D15: C3D1; C4D1; C5D1) and post dose samples collected at C1 and C2 at variable timepoints.
Samples for pharmacokinetics and bioanalytical assessment will be collected as per the PK and bioanalytical blood sample collection schedule at all scheduled cycle visits on Cycle 1 Day 1- less than 1 hour prior to drug infusion,, post-dose at 1, 2, 4, 7, 24 hours and on days 2 (24h post End of Infusion (EOI), 3 (48h post EOI), 4 (72h post EOI), 8 (168h post EOI) and 15 (336h post EOI). Cycle 2 Day 15- less than 1 hour prior to drug infusion , post-dose at 1, 2, 4, 7, 24h and on days 16 (24h post EOI), 17 (48h post EOI), 18 (72h post EOI) and 22 (168h post EOI). Cycle 3, Day 1 and subsequent cycles up to Cycle 5 – less than 1 hour Pre-dose. Schedule may be altered on the basis of evolving data.
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Secondary outcome [4]
423379
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed ORR per iRECIST
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Assessment method [4]
423379
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Timepoint [4]
423379
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Phase 2:
• Confirmed ORR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [5]
423380
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Overall survival
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Assessment method [5]
423380
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Timepoint [5]
423380
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Phase 2:
• Overall survival- assessed every 3 months post EOT.
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Secondary outcome [6]
423902
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Time-to-response (TTR) per RECIST 1.1
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Assessment method [6]
423902
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Timepoint [6]
423902
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Phase 2:
• TTR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [7]
423903
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Disease control rate (DCR) per RECIST 1.1
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Assessment method [7]
423903
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Timepoint [7]
423903
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Phase 2:
• DCR per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [8]
423904
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Progression-free survival (PFS) per RECIST 1.1
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Assessment method [8]
423904
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Timepoint [8]
423904
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Phase 2:
• PFS per RECIST 1.1 - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [9]
423905
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed DOR per iRECIST
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Assessment method [9]
423905
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Timepoint [9]
423905
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Phase 2:
• Confirmed DOR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [10]
423906
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed TTR per iRECIST
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Assessment method [10]
423906
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Timepoint [10]
423906
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Phase 2:
• Confirmed TTR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [11]
423907
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed DCR per iRECIST
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Assessment method [11]
423907
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Timepoint [11]
423907
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Phase 2:
• Confirmed DCR per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Secondary outcome [12]
423908
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Phase 2 - To assess antitumor activity in patients treated with BOS-342
• Confirmed PFS per iRECIST
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Assessment method [12]
423908
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Timepoint [12]
423908
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Phase 2:
• Confirmed PFS per iRECIST - assessed every 8 weeks, until subject comes off treatment and at EoT.
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Eligibility
Key inclusion criteria
Age
1. Patients must be greater than or equal to 18 years, at the time of signing the informed consent.
Disease Characteristics
2. Histologically confirmed diagnosis of locally advanced, unresectable or metastatic HCC for which no standard curative therapy is available, or ineligible to accept/unable to tolerate standard therapy.
3. At least 1 unidimensional radiographically measurable lesion based on RECIST 1.1.
4. Availability of tumor biopsy:
• Phase 1 only: availability of a fresh biopsy or archival tumor samples no older than 2 years prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
• Phase 2 only: availability of fresh tumor biopsy, or an archival tumor sample taken after the last anticancer treatment and prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
5. GPC3 Expression:
• Tumor samples are positive for GPC3 by local or central immunohistochemistry testing
Organ Function and Performance Score within 10 days of treatment initiation
6. Karnofsky score greater than or equal to 50.
7. Adequate renal function as defined by an estimated creatinine clearance of greater than or equal to 60 mL/min/1.73 m2 according to the Cockcroft-Gault equation.
8. Adequate hepatic function defined as:
• total bilirubin less than or equal to 1.5 × upper limit of normal (ULN) or normal conjugated bilirubin.
• aspartate aminotransferase [AST] and alanine aminotransferase [ALT] less than or equal to 3 × ULN, or less than or equal to 5 × ULN if due to liver involvement by tumor.
9. Adequate bone marrow function defined as:
• absolute neutrophil count greater than or equal to 1..5 × 109 cells/L.
• hemoglobin greater than or equal to 9.0 g/dL.
• platelets greater than or equal to 75 × 109 cells/L.
10. Adequate cardiac function defined as ejection fraction greater than 50% by echocardiogram, multigated acquisition (MUGA) or cardiovascular magnetic resonance imaging (MRI).
Pregnancy and Contraception
11. All patients must be willing and able to comply with a highly effective contraceptive method (Appendix 4) during and for 3 months after the treatment period. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Informed Consent
12. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol prior to initiation of any study procedures.
13. Willing and able to participate in the study and comply with all study requirements.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Cancer and Previous Cancer Therapy
1. Any persistent clinically significant greater than or equal to Grade 2 toxicity from prior cancer therapy except alopecia or sensory neuropathy or immunotherapy-related thyroid toxicity requiring replacement therapy.
2. Active CNS metastasis.
Exceptions: patients with stable brain metastases previously treated with surgery, radiotherapy or systemic therapy who are on a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, are eligible to enroll. CNS lesions that have been radiated should not be selected as target lesions for the purposes of RECIST evaluation.
3. Cancer directed therapy (chemotherapy, radiotherapy, biologic, immunotherapy, hormonal therapy or other) within the shorter of 28 days or 5 half-lives, if known, of the first dose of study drug.
Exception: palliative radiotherapy is allowed within 28 days to initiating treatment if associated toxicity resolved to less than or equal to Grade 1. However, lesions treated palliatively should not be selected as target lesions unless there has been clear progression of those lesions since the end of that treatment.
4. Prior or concurrent malignancy other than the malignancy under study, within the last 3 years.
Exception: Patients with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma or other malignancy for which there is very low risk of recurrence or progression are eligible.
Prior/Concomitant Therapy
5. Major surgery within 28 days prior to the first dose of study drug.
6. Systemic corticosteroid therapy or any other form of systemic immunosuppressive medication within 1 week prior to the first dose of study drug.
Exceptions: corticosteroid use as a premedication for IV contrast, transfusion therapy or prednisone less than or equal to 10 mg or equivalent per day for adrenal replacement or for patients with CNS disease, is permitted.
7. Live vaccine within 30 days prior to first day of treatment.
Infections
8. Active hepatitis B, defined as hepatitis B virus (HBV) surface antigen positive or HBV deoxyribonucleic acid positive.
9. Active hepatitis C, defined as positive hepatitis C virus (HCV) antibody with positive HCV ribonucleic acid (RNA).
10. Known infection with human immunodeficiency virus (HIV), unless meeting all of the following criteria:
• Stable on antiretroviral therapy (ART) for at least 4 weeks.
• Adherence to ART during study therapy.
• HIV viral load of less than 400 copies/mL at Screening (or undetectable per local criteria).
• CD4 counts greater than or equal to 200/microliter.
11. Evidence or history of active or latent tuberculosis (TB) infection, defined as any 1 of the following:
• Current clinical, radiographical, or laboratory evidence of active TB.
• History of active TB.
• Positive QuantiFERON-TB Gold In-Tube or other diagnostic test in the absence of clinical manifestations.
12. Active infection being treated with systemic antibiotic, antiviral, or antifungal therapy.
Pregnancy and Breastfeeding
13. Pregnancy: Negative serum pregnancy test for females of child-bearing potential are required within 48 hours before the first dose of study intervention.
14. Breastfeeding or storage of breast milk.
Organ Function
15. Uncontrolled or significant cardiovascular disease, including:
• myocardial infarction, unstable angina or stroke/transient ischemic attack within the past 6 months.
• history of clinically significant arrythmias (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation or torsade de pointes).
• history of other clinically significant heart disease (e.g., New York Heart Association (NYHA) Class II or greater congestive heart failure, pericarditis, cardiac amyloidosis, significant pericardial effusion).
16. Liver cirrhosis classified as Child-Pugh Class B (greater than 7) or C.
Concurrent Conditions
17. Uncontrolled or severe concurrent medical condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
18. Uncontrolled intercurrent illness or psychiatric illness/social situation that would limit compliance with study requirements.
19. Clinically significant autoimmune disease, or history of greater than or equal to Grade 3 immune-mediated adverse event due to a checkpoint inhibitor or similar therapy.
20. Solid organ transplant.
Other Exclusions
21. Patient not available to complete all protocol required study visits or procedures to the best of the patient’s ability and Investigator’s knowledge.
22. History or evidence of any other clinically significant condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator, would be a risk to patient safety or interfere with the study evaluation, procedures, or completion.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Nil
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
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Other design features
Nil
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Phase
Phase 1 / Phase 2
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Type of endpoint/s
Safety
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Statistical methods / analysis
Continuous measures will be summarized using number of patients with an observation(s),
mean, median, standard deviation, Q1 and Q3 quartiles, minimum and maximum value. Categorical measures will be summarized by number and percentage of patients per category.
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
9/08/2023
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Actual
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Date of last participant enrolment
Anticipated
23/10/2025
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Actual
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Date of last data collection
Anticipated
31/10/2026
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Actual
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Sample size
Target
81
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,SA
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Recruitment hospital [1]
24363
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St Vincent's Hospital (Darlinghurst) - Darlinghurst
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Recruitment hospital [2]
24364
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Flinders Medical Centre - Bedford Park
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Recruitment hospital [3]
24595
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Royal Prince Alfred Hospital - Camperdown
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Recruitment postcode(s) [1]
39947
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2010 - Darlinghurst
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Recruitment postcode(s) [2]
39948
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5042 - Bedford Park
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Recruitment postcode(s) [3]
40190
0
2050 - Camperdown
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Recruitment outside Australia
Country [1]
25591
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Korea, Republic Of
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State/province [1]
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South Korea
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Country [2]
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Taiwan, Province Of China
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State/province [2]
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Taiwan
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Funding & Sponsors
Funding source category [1]
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Commercial sector/Industry
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Name [1]
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Boston Pharmaceuticals, Inc.
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Address [1]
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Boston Pharmaceuticals, Inc.
55 Cambridge Parkway,
Suite 400 Cambridge,
MA 02142 USA
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Country [1]
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United States of America
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Primary sponsor type
Commercial sector/Industry
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Name
Boston Pharmaceuticals, Inc.
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Address
Boston Pharmaceuticals, Inc.
55 Cambridge Parkway,
Suite 400 Cambridge,
MA 02142 USA
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Country
United States of America
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Secondary sponsor category [1]
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Commercial sector/Industry
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Name [1]
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Pharm-Olam International Pty. Ltd.
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Address [1]
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Pharm-Olam International Pty. Ltd.
Level 12, 60 Castlereagh Street
Sydney, NSW 2000
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Country [1]
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Australia
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
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Bellberry Human Reasearch Ethics Committee
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Ethics committee address [1]
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123 Glen Osmond Rd. Eastwood SA 5063
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Ethics committee country [1]
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Australia
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Date submitted for ethics approval [1]
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29/03/2023
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Approval date [1]
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29/05/2023
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Ethics approval number [1]
312695
0
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Summary
Brief summary
This is a Phase 1/2, open label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK) and clinical activity of escalating doses of BOS-342 monotherapy in patients with Hepatocellular Carcinoma (HCC) or other Glypican 3 (GPC3)-expressing tumors.
Who is it for?
You may be eligible for this study if you are aged 18 years or older, have histologically confirmed diagnosis of locally advanced, unresectable or metastatic HCC for which no standard curative therapy is available or other Glypican 3 (GPC3)-expressing tumors.
Study details
There are 2 Phases in this study. In Phase 1, all participants will be enrolled into small groups. Each group will receive a dose of BOS-342 administered intravenously (IV) every 2 weeks until radiologically documented progressive disease (PD), unacceptable toxicity, or occurrence of any criterion for withdrawal from the study or the study treatment. There will be up to six different dose levels tested to identify the highest tolerated dose of BOS-342.
In Phase 2, participants will receive a dose level and schedule that is deemed safe and tolerable as determined in discussion among the Sponsor, Medical Monitor, and Safety Review Team (SRT) in Phase 1. Observations related to safety including TEAEs occurring within and beyond the DLT window, tolerability, compliance, PK, pharmacodynamic, ADA and preliminary efficacy will be included in the rationale supporting the selection of the Recommended Phase 2 dose (RP2D).
Safety, tolerability, PK and clinical activity evaluations will be assessed in both phases. After completion of the Safety Follow-up visit, patients will be contacted every 3 months for survival status following the last dose of study drug.
It is hoped that the information obtained from this study may help treat and improve the survival of future patients with HCC and other tumors
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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A/Prof Hao-Wen Sim
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Address
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St Vincent's Hospital Sydney
370 Victoria Street,
Darlinghurst, NSW 2010
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Country
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Australia
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Phone
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+61 2 9355 5737
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Fax
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Email
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[email protected]
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Contact person for public queries
Name
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Mr Harmeet Singh
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Address
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Pharm-Olam International (Australia) Pty. Ltd.
Level 12
60 Castlereagh Street
Sydney, New South Wales 2000
AUSTRALIA
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Country
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Australia
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Phone
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+61 2 9188 0500
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Name
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Dr Galit Rosen
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Address
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VP Clinical Development
Boston Pharmaceuticals
55 Cambridge Parkway, Suite 400
Cambridge, MA 02142
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Country
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United States of America
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Phone
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+1 857 404 2232
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Fax
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Email
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
The data collected for each participant will be recorded and reported in a blinded manner, hence, it is not possible to provide individual participant data to be shared.
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
No additional documents have been identified.
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