Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001689167
Ethics application status
Approved
Date submitted
21/11/2019
Date registered
2/12/2019
Date last updated
2/02/2022
Date data sharing statement initially provided
2/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of ALMB-0166 administered intravenously to assess tolerability and metabolism of the study drug in healthy participants.
Scientific title
A Phase 1 Single Center, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ALMB-0166 Administered to Healthy Subjects
Secondary ID [1] 299653 0
ALMB-0166-AU-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal cord injury 314988 0
Condition category
Condition code
Injuries and Accidents 313321 313321 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a 2-part, Phase I, single-centre, randomised, double-blind, placebo-controlled, sequential cohort study of single and multiple ascending doses of ALMB-0166 or placebo administered by intravenous infusion to healthy adult participants. Participant population to be enrolled in SAD and MAD parts of the study will be mutually exclusive. Part 1 will be single ascending dose (SAD) which will involve at least 4 cohorts testing single incremental doses of 1 mg/Kg, 3 mg/Kg, 10 mg/Kg and 25 mg/Kg. Part 2 of the study will be a Multiple Ascending Dose (MAD) involving up to 4 dosing levels to be determined after review of Part 1 which will be administered intravenously on Days 1, 8, 15 and 21. Dose escalation will be determined by a Safety Review Committee (SRC) that will review all the safety data available from the previous cohort. In both parts, the SRC should make a recommendation as to whether the next dose should be escalated or reduced, or additional subjects should be dosed in a same dose level of a cohort.

Adherence to the protocol intervention for SAD and MAD parts of the study will be performed through direct observation by study personnel since the investigational product will be administered in the phase I unit.
Intervention code [1] 315911 0
Treatment: Drugs
Comparator / control treatment
Placebo (0.9% sodium chloride)
Control group
Placebo

Outcomes
Primary outcome [1] 321806 0
To establish the safety and tolerability of single ascending doses of ALMB-0166 relative to placebo, as assessed by physical examination, vital signs, pulse oximetry, safety labs, ECG, immune reaction markers and adverse events which will be monitored daily including signs of infusion related reactions, infections, flu-like symptoms, rash, myalgia and arthralgia, fever and chills from the day of study drug administration through to discharge from the clinical unit.
Timepoint [1] 321806 0
Assessed during Single Ascending Dose (Part 1) at the following timepoints:
- Physical examination at Screening, Day -1, Days 2, 4, 8, 15, 29 and 57;
- Vital signs at Screening, Day -1, Days 1, 2, 3 and 4;
- Pulse oximetry on Day 1 pre-dose and at 30 mins, 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose;
- Safety labs at Screening, Day -1, Days 1, 2, 3, 4, 8, 15, 29 and 57;
- ECG at Screening, Day -1, Days 1, 2 and 57;
- Immune reaction markers on Day -1 and Day 1;
- Adverse events from the day of study drug administration through to study completion or early termination and throughout the post-study follow-up period for serious adverse events (i.e. until resolution, stabilization or the participant is lost to follow-up)
Primary outcome [2] 321807 0
To recommend dosing regimens of ALMB-0166 for future patient studies, as assessed by physical examination, vital signs, pulse oximetry, safety labs, ECG, immune reaction markers, adverse events, pharmacokinetics, and anti drug antibodies.
Timepoint [2] 321807 0
Assessed during Multiple Ascending Dose (Part 2) at the following timepoints:
- Physical examination at Screening, Day -1, Days 2, 9, 16, 23 and Weeks 6, 8 and 12;
- Vital signs at Screening, Days 1, 2, 8, 9, 15, 16, 22, 23 and Weeks 6, 8 and 12;
- Pulse oximetry on each dosing day (Days 1, 8, 15, 22) at pre-dose, 30 min, 1 hr, 1.5 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose.
- Safety labs at Screening, Day -1, Days 1, 2, 7, 14, 21, 23 and Weeks 6, 8 and 12.
- ECG at Screening, Day -1, Days 1, 8, 15, 22 and Week 12;
- Immune reaction markers at Day -1, Days, 8, 15 and 22;
- Adverse events from the day of first study drug administration through to study completion or early termination and throughout the post-study follow-up period for serious adverse events (i.e. until resolution, stabilization or the participant is lost to follow-up)
Secondary outcome [1] 376254 0
To evaluate the pharmacokinetics of ALMB-0166 via serum Meso Scale Discovery assay following single and multiple dose administrations.
Pharmacokinetic parameters to be assessed include Cmax, Tmax, t1/2, AUC0-inf, AUC0-last, CL, RCmax and Vd; additional parameters may be analysed as appropriate.
Timepoint [1] 376254 0
Assessed during Single Ascending Dose (Part 1) on Day 1 (pre-dose, then within 5 mins following infusion, at 1 hr, 4 hr and 8 hr post-dose and on Days 2, 3, 4, 8, 15, 29 and 57. Assessed during Multiple Ascending Dose (Part 2) on days 1, 8, 15 and 22 at pre-dose and 1 hr post-dose..
Secondary outcome [2] 376255 0
To evaluate the immunogenicity of ALMB-0166 via anti-drug antibodies (ADA) using Meso Scale Discovery (MSD) assay and immune markers in serum via Elisa following a single and multiple dose administrations
Timepoint [2] 376255 0
Single Ascending Dose (Part 1): ADAs assessed at baseline (day -1) and days 15, 29 and 57. Immune markers to be assessed at baseline and on Day 1 at 10 min, 2h, 6h after end of infusion and if clinically indicated at other time points.

Multiple Ascending Dose (Part 2): ADAs assessed at baseline (Day -1) and Days 1, 8, 15, 22 and Week 12. Immune markers to be assessed at baseline, on days 8, 15 and 22 post-dose and at other time points if clinically indicated.

Eligibility
Key inclusion criteria
Participants are eligible for the study only if all of the following criteria apply:

1. Healthy male or female subjects between 18 and 55 years, inclusive
2. Negative urine drug screen (UDS) at Screening, and if the UDS is positive, retest it
3. Subject is in good health as indicated by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG), and all abnormal findings are assessed as Not Clinically Significant by the Investigator.
4. Body weight between 45 and 110 kg inclusive, and BMI between 18 and 34 kg/m2 inclusive at Screening. The maximum body weight is 100 kg for subjects to be enrolled in the dose level 25 mg/kg, or above if applicable.
5. Subject is able to speak, read, and understand the language in which the trial is conducted and voluntarily provide written informed consent to participate in the study.
6. If female, the subject must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at check-in to the Research Unit for the first dosing visit or a negative serum pregnancy test 24 hours prior to dosing at subsequent visits in Part 2 and is not nursing or planning a pregnancy.
7. If female, subject must be:
a. Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or
b. Of childbearing potential and practicing an acceptable form of birth control (defined as the use of any two of the following: an intrauterine device; a barrier method; condoms, any form of hormonal contraceptives; or abstinence from sexual intercourse) starting 60 days prior to dosing and continuing 30 days following the last treatment.
c. Of non-childbearing potential (ie, postmenopausal for at least 1 year with an elevated follicle stimulating hormone (FSH) level consistent with post-menopausal status).
8. If male, subject must be surgically or biologically sterile. If not sterile, the subject must agree to use an acceptable form of birth control with sexual partner (as described in inclusion criteria #7b) or abstain from sexual relations for 30 days following the last treatment.
9. Negative test results for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C at Screening.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

1. History of any drug allergy, hypersensitivity, or intolerance to any drug product that in the opinion of the investigator would place the subject at particular risk and compromise the safety of the subject in the study.
2. History or current diagnosis of substance dependence (except nicotine and caffeine) or alcohol abuse, according to the criteria of DSM-IV-TR.
3. History of traumatic brain injury (TBI) and concussion
4. Subject with a high frequency migraine
5. Subject who practices contact sports within the past 6 months
6. On fluid restriction.
7. Plan to participate in another clinical trial while enrolled in this study and/or who have received an investigational drug and/or device within 30 days prior to admission.
8. Have donated or had significant loss of whole blood (greater than 480 mL) within 30 days or plasma within 14 days prior to admission.
9. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, psychiatric disease, or any other condition, that in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
10. Receiving any prescription medication(s) within 14 days of dose administration, or any non-prescribed or topical medication (including any herbal product) within 7 days prior to dose administration.
11. Subject who smokes and is unable to stop smoking during the in-patient observation period in the Research Unit.
12. Unwilling to abstain from alcohol for at least 24 hours prior to dosing with study medication until the time of discharge from the study unit, and at least 24 hours prior to each ambulatory visit.
13. QTcF >450 msec for male subjects or >470 msec for female subjects on 3 consecutive ECG recordings conducted at Screening or Baseline.
14. Females who are breastfeeding (if unwilling to stop for the first 60 days following the start of dosing) or who are pregnant.
15. With one of the following conditions where a MRI scan cannot be performed:
a. Any electrically, magnetically or mechanically activated implant (e.g. cardiac pacemaker, insulin pump biostimulator, neurostimulator, cochlear implant, and hearing aids)
b. Intracranial aneurysm clips (unless made of titanium)
c. Ferromagnetic surgical clips or staples.
d. Metallic foreign body in the eye
e. Metal shrapnel or bullet
f. Other conditions that make the subject not suitable for receiving a MRI scan, per PI’s judgement

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealed. Unblinded pharmacist at the site who holds the randomisation schedule will assign the treatment allocation according to the randomisation schedule upon preparation of the study drug on Day -1.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation schedule will be prepared by a statistician prior to study intervention.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other
Other design features
Sequential cohort study of single and multiple doses of ALMB-0166 or placebo.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Categorical variables will be summarized by the number and percent of subjects in each category. Continuous variables will be summarized as summary statistics. Analysis of all safety data will be performed on the Safety Population and will be presented by the treatment received. Regarding PK analysis the concentrations of ALMB-0166 will be summarized using descriptive statistics (arithmetic means, SDs, coefficients of variation, sample size, minimum, maximum, and geometric means). The following PK parameters will be calculated using noncompartmental methods: Cmax, Tmax, t1/2, AUC0-inf, AUC0-last, CL, RCmax and Vd; additional parameters or PK analysis may be done as appropriate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/12/2019
Actual
6/12/2019
Date of last participant enrolment
Anticipated
Actual
29/10/2020
Date of last data collection
Anticipated
31/03/2021
Actual
31/12/2020
Sample size
Target
36
Accrual to date
Final
46
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15061 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 28351 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 304124 0
Commercial sector/Industry
Name [1] 304124 0
AlaMab Therapeutics, Inc.
Country [1] 304124 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Avance Clinical Pty Ltd
Address
Level 1, 2 Ann Nelson Drive
Thebarton SA 5031
Country
Australia
Secondary sponsor category [1] 304340 0
None
Name [1] 304340 0
Address [1] 304340 0
Country [1] 304340 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304611 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 304611 0
Ethics committee country [1] 304611 0
Australia
Date submitted for ethics approval [1] 304611 0
14/08/2019
Approval date [1] 304611 0
18/10/2019
Ethics approval number [1] 304611 0
2019-07-658

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97578 0
Dr Charlotte Lemech
Address 97578 0
Scientia Clinical Research Ltd, Bright Building, Levels 5 & 6, corner High & Avoca Street, Randwick, 2031 NSW.
Country 97578 0
Australia
Phone 97578 0
+612 9382 5807
Fax 97578 0
Email 97578 0
[email protected]
Contact person for public queries
Name 97579 0
Yanfeng Zhang
Address 97579 0
AlaMab Therapeutics Inc.
A subsidiary of CSPC Pharmaceutical Group, Ltd.
11550 West Interstate 10
San Antonio, TX 78230
USA
Country 97579 0
United States of America
Phone 97579 0
+1 517 667 0767
Fax 97579 0
Email 97579 0
[email protected]
Contact person for scientific queries
Name 97580 0
Charlotte Lemech
Address 97580 0
Scientia Clinical Research Ltd, Bright Building, Levels 5 & 6, corner High & Avoca Street, Randwick, 2031 NSW.
Country 97580 0
Australia
Phone 97580 0
+612 9382 5807
Fax 97580 0
Email 97580 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and intellectual property considerations


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.