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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04952753
Registration number
NCT04952753
Ethics application status
Date submitted
28/06/2021
Date registered
7/07/2021
Date last updated
25/06/2024
Titles & IDs
Public title
Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC
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Scientific title
An Open-label, Multi-center, ph II Platform Study Evaluating the Efficacy and Safety of NIS793 and Other New Investigational Drug Combinations With SOC Anti-cancer Therapy for the 2L Treatment of Metastatic Colorectal Cancer (mCRC)
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Secondary ID [1]
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2021-000553-40
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Secondary ID [2]
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CNIS793E12201
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Universal Trial Number (UTN)
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Trial acronym
daNIS-3
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer
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Condition category
Condition code
Cancer
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Bowel - Back passage (rectum) or large bowel (colon)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - NIS793
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Modified FOLFOX6
Treatment: Drugs - FOLFIRI
Treatment: Drugs - Tislelizumab
Experimental: Safety run-in: NIS793+SOC (Investigational arm 1) - In the safety run-in part for investigational arm 1, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 to confirm the RP2D of the NIS793
Experimental: Expansion: NIS793+SOC (Investigational arm 1) - In the expansion part, participants in the investigational arm 1 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 at the RP2D defined in the safety run-in
Active comparator: Expansion: SOC (control arm) - In the expansion part, participants in the control arm will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI)
Experimental: Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) - In the safety run-in part for investigational arm 2, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI), NIS793 and tislelizumab to confirm the RP2D of NIS793.
Experimental: Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2) - In the expansion part, participants in the investigational arm 2 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FLOFOX6 or FOLFIRI) with NIS793 and tislelizumab at the RP2D for NIS793 defined in the safety run-in
Treatment: Drugs: NIS793
Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part.
Treatment: Drugs: Bevacizumab
Bevacizumab will be administered IV
Treatment: Drugs: Modified FOLFOX6
5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and oxaliplatin \[administered IV\]
Treatment: Drugs: FOLFIRI
5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and irinotecan \[administered IV\]
Treatment: Drugs: Tislelizumab
Investigational drug tislelizumab will be administered intravenously (IV).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
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Assessment method [1]
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Percentage of participants with DLTs during the first cycle of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 with or without tislelizumab in combination with Bevacizumab and modified FOLFOX6/ FOLFIRI and meets protocol defined DLT criteria.
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Timepoint [1]
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Up to 4 weeks
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Primary outcome [2]
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Expansion: Progression-free survival (PFS) by investigator assessment per RECIST 1.1
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Assessment method [2]
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PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.
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Timepoint [2]
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From randomization up to disease progression or death, assessed up to approximately 12 months
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Secondary outcome [1]
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Safety run-in: Percentage of participants with Adverse Events (AEs)
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Assessment method [1]
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Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
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Timepoint [1]
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Up to approximately 12 months
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Secondary outcome [2]
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Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug
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Assessment method [2]
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Tolerability measured by the percentage of subjects who have dose adjustments (interruptions or reductions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
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Timepoint [2]
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Upto approximately 12 months
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Secondary outcome [3]
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Safety run-in: Dose intensity of investigational drug
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Assessment method [3]
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Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
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Timepoint [3]
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0
Up to approximately 12 months
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Secondary outcome [4]
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Safety run-in: PFS by investigator assessment per RECIST 1.1
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Assessment method [4]
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PFS defined as the time from the date of enrollment to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.
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Timepoint [4]
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From enrollment up to disease progression or death, assessed up to approximately 12 months
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Secondary outcome [5]
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Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1
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Assessment method [5]
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ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
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Timepoint [5]
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Up to approximately 12 months
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Secondary outcome [6]
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Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1
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Assessment method [6]
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DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
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Timepoint [6]
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Up to approximately 12 months
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Secondary outcome [7]
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Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1
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Assessment method [7]
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DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause
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Timepoint [7]
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From first documented response up to disease progression or death, assessed up to approximately 12 months
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Secondary outcome [8]
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Safety run-in part: Overall Survival (OS)
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Assessment method [8]
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OS is defined as the time from the date of enrollment to date of death due to any cause.
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Timepoint [8]
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From enrollment up to death, assessed up to approximately 12 months
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Secondary outcome [9]
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Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1
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Assessment method [9]
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TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
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Timepoint [9]
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From enrollment up to first documented response, assessed up to approximately 12 months
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Secondary outcome [10]
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Expansion: Percentage of participants with Adverse Events (AEs)
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Assessment method [10]
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Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
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Timepoint [10]
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Up to approximately 12 months
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Secondary outcome [11]
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Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug
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Assessment method [11]
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Tolerability measured by the percentage of subjects who have dose adjustments (interruptions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
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Timepoint [11]
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Up to approximately 12 months
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Secondary outcome [12]
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Expansion: Dose intensity of investigational drug
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Assessment method [12]
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Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+Tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
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Timepoint [12]
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Up to approximately 12 months
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Secondary outcome [13]
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Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1
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Assessment method [13]
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ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
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Timepoint [13]
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Up to approximately 12 months
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Secondary outcome [14]
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Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1
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Assessment method [14]
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DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
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Timepoint [14]
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Up to approximately 12 months
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Secondary outcome [15]
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Expansion: Duration of response (DOR) by investigator assessment per RECIST 1.1
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Assessment method [15]
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DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause
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Timepoint [15]
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From first documented response up to disease progression or death, assessed up to approximately 12 months
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Secondary outcome [16]
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Expansion part: Overall Survival (OS)
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Assessment method [16]
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OS is defined as the time from the date of enrollment to date of death due to any cause.
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Timepoint [16]
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From randomization up to death, assessed up to approximately 12 months
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Secondary outcome [17]
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Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1
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Assessment method [17]
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TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
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Timepoint [17]
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From enrollment up to first documented response, assessed up to approximately 12 months
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Secondary outcome [18]
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Maximum concentration (Cmax) of NIS793
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Assessment method [18]
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Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793
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Timepoint [18]
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From the date of first study drug intake up to approximately 12 months
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Secondary outcome [19]
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Maximum concentration (Cmax) of tislelizumab
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Assessment method [19]
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Blood samples will be collected at indicated time-points for analysis of Cmax of tislelizumab
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Timepoint [19]
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From the date of first study drug intake up to approximately 12 months
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Secondary outcome [20]
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Trough Concentration (Ctrough) of NIS793
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Assessment method [20]
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Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793
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Timepoint [20]
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From the date of first study drug intake up to approximately 12 months
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Secondary outcome [21]
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Trough Concentration (Ctrough) tislelizumab
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Assessment method [21]
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Blood samples will be collected at indicated time-points for analysis of Ctrough of tislelizumab
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Timepoint [21]
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From the date of first study drug intake up to approximately 12 months
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Secondary outcome [22]
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Antidrug antibodies (ADA) at baseline
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Assessment method [22]
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Prevalence of ADA (anti-NIS793, anti-tislelizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline
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Timepoint [22]
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Baseline
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Secondary outcome [23]
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ADA incidence on treatment
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Assessment method [23]
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Incidence of ADA (anti-NIS793, anti-tislelizumab) on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
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Timepoint [23]
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From the date of first study drug intake up to approximately 12 months
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Eligibility
Key inclusion criteria
Key
* Participants age 18 or older with histologically or cytologically confirmed (by local laboratory and local clinical guidelines) metastatic colorectal adenocarcinoma that is not amenable to potentially curative surgery in the opinion of the investigator and progressed on or within 6 months after the last dose of one prior line of systemic anti-cancer therapy administered for metastatic disease.
* Presence of at least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
* Adequate organ function (assessed by central laboratory for eligibility).
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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
* Previously administered TGF-ß targeted therapies or anti-cancer immunotherapy.
* Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAFV600 mutation positive colorectal cancer.
* Known complete or partial dipyrimidine dehydrogenase (DPD) enzyme deficiency (testing for DPD enzyme deficiency is not mandatory unless required by local regulations and can be conducted at a local laboratory).
* For participants treated with irinotecan: Known history or clinical evidence of reduced UGT1A1 activity (testing for UGT1A1 status is not mandatory unless required by local regulations and can be conducted at a local laboratory).
* Participants who have not recovered from a major surgery performed prior to start of study treatment or have had a major surgery within 4 weeks prior to start of study treatment.
* Impaired cardiac function or clinically significant cardio-vascular disease.
* Participants with conditions that are considered to have a high risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
* Stroke or transient ischemic attack, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before start of study treatment.
* Pregnant or breast-feeding women.
* Women of childbearing potential, unless willing to use highly effective contraception methods during treatment and after stopping study treatments as required.
Other inclusion/exclusion criteria may apply
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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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
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
15/11/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
12/09/2024
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Actual
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Sample size
Target
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Accrual to date
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Final
204
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Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
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Recruitment hospital [1]
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Novartis Investigative Site - Adelaide
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Recruitment hospital [2]
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Novartis Investigative Site - Bendigo
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Recruitment hospital [3]
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Novartis Investigative Site - Perth
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Recruitment postcode(s) [1]
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5000 - Adelaide
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Recruitment postcode(s) [2]
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3550 - Bendigo
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Recruitment postcode(s) [3]
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6009 - Perth
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Michigan
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United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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Tennessee
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United States of America
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Texas
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0
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Belgium
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State/province [7]
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Bruxelles
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Belgium
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Leuven
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Canada
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State/province [9]
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Ontario
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Canada
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Quebec
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Czechia
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State/province [11]
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Czech Republic
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Czechia
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State/province [12]
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CZE
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Czechia
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State/province [13]
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Praha 4
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France
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State/province [14]
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Avignon
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France
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Creteil
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France
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State/province [16]
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Nantes Cedex 1
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Germany
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State/province [17]
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Berlin
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Country [18]
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Germany
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State/province [18]
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Bochum
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Country [19]
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Germany
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State/province [19]
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Dresden
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Hamburg
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Germany
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Ulm
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Hong Kong
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Pokfulam
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Hong Kong
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Shatin New Territories
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Israel
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Haifa
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Israel
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State/province [27]
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Petach Tikva
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Italy
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MI
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Japan
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Aichi
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Japan
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Chiba
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Japan
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State/province [31]
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Kanagawa
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Japan
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Osaka
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Japan
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Toyama
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Korea, Republic of
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Seoul
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Catalunya
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Spain
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Madrid
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Switzerland
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St. Gallen
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Taiwan
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Tainan
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Taiwan
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Taipei
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United Kingdom
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Scotland
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United Kingdom
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Cambridge
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United Kingdom
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State/province [45]
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Oxford
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to evaluate the preliminary efficacy and safety of NIS793 and other novel investigational combinations with standard of care (SOC) anti-cancer therapy vs SOC anti-cancer therapy for the second line treatment of mCRC.
This study aims to explore whether different mechanisms of action may reverse resistance and improve responsiveness to the currently considered SOC anti-cancer therapy in the second line metastatic colorectal cancer (mCRC) setting.
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Trial website
https://clinicaltrials.gov/study/NCT04952753
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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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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/study/NCT04952753
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