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Trial registered on ANZCTR


Registration number
ACTRN12618000121268
Ethics application status
Approved
Date submitted
15/01/2018
Date registered
29/01/2018
Date last updated
29/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Dose of Getagozumab in Healthy Volunteers
Scientific title
A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Dose of Getagozumab in Healthy Volunteers
Secondary ID [1] 293650 0
Gmax_GETA_SAD_01
Universal Trial Number (UTN)
U1111-1203-6057
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plumonary Arterial Hypertension 305939 0
Condition category
Condition code
Cardiovascular 305132 305132 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be a single-centre, double-blind, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK of GMA301 (thereafter referred to as getagozumab), in healthy subjects. Four sequential dosing cohorts, each with 6 subjects receiving getagozumab and 2 subjects receiving placebo (total of 32 subjects), will be given increasing intravenous infusion,single doses of getagozumab. The doses administered will be 75, 200, 500, and 1000 mg, or matching placebo at Day 1 and monitor the adherence to the intervention by direct observation.
As a conservative measure for the safety of healthy human subjects in this Phase 1 study of getagozumab, sentinel dosing is proposed for each group. Two sentinel subjects (1:1 active to placebo) will be dosed first and the remaining 6 subjects in the cohort will be dosed 7 days later, followed by at least 12 days prior to the next cohort dosing. Before proceeding to the next cohort, the Safety Review Committee (SRC; including an independent SRC member or SRC members) will have to review all the clinical data of the just finished cohort and approve the dosing of the next cohort.
After Screening (Screening Period of 28 days), eligible subjects who meet the inclusion criteria and none of the exclusion criteria will be randomized into the study. A computer generated randomization schedule will be used. The treatment period will last up to 8 weeks, followed by a 2 week follow-up period. Blood sampling for PK will be performed at: predose, 4 hours (h), 8h, 24h, 72h, 168h (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 (Week 8), and Week 10. At each time point, 3 mL of whole blood will be collected for PK analyses.
Intervention code [1] 299913 0
Treatment: Drugs
Comparator / control treatment
Placebo, containing the same constituents and excipients as Getagozumab Injection, apart from the active components (Getagozumab).
Control group
Placebo

Outcomes
Primary outcome [1] 304293 0
Adverse events (AEs) will be assessed by laboratory parameters, vital signs, physical examination, ECG, routine clinical observations.
Timepoint [1] 304293 0
Baseline through 10 weeks, daily.
Primary outcome [2] 304455 0
The immunogenicity samples will be tested for the presence of ADAs. The results will be listed and summarized by treatment of serum assays for frequency of occurrence. Moreover, to evaluate the development of immunogenicity, shift tables will be used to compare the results obtained at Baseline with the results at Weeks 2, 4, and 10.
The details of the immunogenicity analysis will be outlined in greater detail in the SAP.
Timepoint [2] 304455 0
Baseline (Day 1), and at week2, 4, 10 (primary timepoint) after intervention commencement.
Secondary outcome [1] 342014 0
Assess the PK profile including AUC0-t, AUC0-inf, Cmax, Tmax, t1/2.
Timepoint [1] 342014 0
Predose, 4h, 8h, 24h, 72h, 168h (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 (Week 8), and Week 10.

Eligibility
Key inclusion criteria
• Healthy male and female subjects 18 to 60 years old, inclusive, at the time of Screening, as confirmed by medical history, physical examination, and routine laboratory tests.
• Routine clinical laboratory tests within normal range or minor deviations not deemed clinically important by the investigator.
• Body mass index (BMI) of 18.5 kg/m2 to 30.0 kg/m2, inclusive, at Screening.
• Blood pressure (BP) and pulse rate at Screening within normal range (ie, systolic 90-140 mmHg, diastolic 60-90 mmHg, and pulse rate 40-100 bpm). Up to 2 additional measurements may be taken after an appropriate resting interval (at least 10 minutes) at Screening to confirm eligibility.
• Female subjects (or female partners of male subjects) of childbearing potential must have a negative serum pregnancy test result within 48 hours prior to receiving study drug (female subjects only) and must agree to avoid pregnancy by using an accepted form of highly effective contraception during the study and for 6 months after study drug administration.
• Negative screen for drugs of abuse and alcohol at Screening.
• Male subjects must agree not to donate sperm during the study and for 6 months after study drug administration.
Male subjects must agree to avoid causing pregnancy by using a reliable method of birth control during the study and for 6 months after study drug administration.
• Give written informed consent to participate in the study prior to any screening procedures.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Presence or history of any clinically significant chronic condition of the neurological, respiratory, cardiovascular, gastrointestinal, urogenital, reproductive, musculoskeletal, endocrine system or cancer .
• Clinically significant (as judged by the investigator) presence of acute illness (eg, gastrointestinal illness, infection such as influenza, upper respiratory tract infection) upon admission to the study site
• Alanine aminotransferase and/or aspartate aminotransferase above the upper limit of normal.
• Hemoglobin below lower limit of normal.
• Positive serology test results for hepatitis B, hepatitis C, and/or human immunodeficiency virus at Screening.
• Clinically significant abnormality in the 12-lead electrocardiogram (ECG) as judged by the investigator.
• Currently enrolled in a clinical trial or have been enrolled in a clinical trial involving an investigational product or medical device that acts on the cardiovascular system, respiratory system, or endocrine system within at least 1 month with 5 half-lives of the tested agent (whichever was shorter) prior to Screening.
• Women who are pregnant, intend to become pregnant, or are lactating.
• History of type 1 hypersensitivity or severe cutaneous adverse reaction to any medication, or history of significant atopy.
• Use of prescription medications or over-the-counter medications within 7 days prior to study drug administration, with the exception of simple analgesics such as paracetamol and routine vitamins.
• Donated more than 500 mL of blood within 4 weeks prior to study enrollment, or donated plasma or participated in a plasmapheresis program within 7 days of study drug administration.
• Average weekly alcohol intake that exceeds 14 units per week (males ) or 7 units (females) per week, or are unwilling to stop alcohol consumption for 24 hours prior to study drug dosing until the completion of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine;1.5 oz or 45 mL of distilled spirits).
• Current smoker, or a history of regular (more than weekly) use of tobacco or nicotine-containing products within 2 months prior to Screening.
• In the opinion of the investigator or sponsor, deemed unsuitable for inclusion in the study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 298267 0
Commercial sector/Industry
Name [1] 298267 0
Gmax Biopharm Australia Pty Ltd.
Address [1] 298267 0
Suite 4, Level 2, 189 Kent Street
Sydney, NSW 2000, Australia
Country [1] 298267 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gmax Biopharm Australia Pty Ltd.
Address
Suite 4, Level 2, 189 Kent Street
Sydney, NSW 2000, Australia
Country
Australia
Secondary sponsor category [1] 297385 0
None
Name [1] 297385 0
Address [1] 297385 0
Country [1] 297385 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299269 0
Bellberry Ethics Committee
Ethics committee address [1] 299269 0
129 Glen Osmond Rd, Eastwood SA 5063, Australia.
Ethics committee country [1] 299269 0
Australia
Date submitted for ethics approval [1] 299269 0
20/10/2017
Approval date [1] 299269 0
15/12/2017
Ethics approval number [1] 299269 0

Summary
Brief summary
This study will be a single-centre, double-blind, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK of GMA301 (thereafter referred to as getagozumab), in healthy subjects. Four sequential dosing cohorts, each with 6 subjects receiving getagozumab and 2 subjects receiving placebo (total of 32 subjects), will be given increasing single doses of getagozumab. sentinel dosing is proposed for each group. Two sentinel subjects (1:1 active to placebo) will be dosed first and the remaining 6 subjects in the cohort will be dosed 7 days later, followed by at least 12 days prior to the next cohort dosing.
After Screening (Screening Period of 28 days), eligible subjects who meet the inclusion criteria and none of the exclusion criteria will be randomized into the study. A computer-generated randomization schedule will be used. The treatment period will last up to 8 weeks, followed by a 2-week follow-up period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79854 0
Dr Sepehr Shakib
Address 79854 0
CMAX Clinical Research Ltd, Level 5, 18a North Terrace, Adelaide, South Australia 5000, Australia
Country 79854 0
Australia
Phone 79854 0
+61 8 8222 2763
Fax 79854 0
Email 79854 0
Sepehr.Shakib@health.sa.gov.au
Contact person for public queries
Name 79855 0
Ms Jiebo Gu
Address 79855 0
Gmax Biopharm, LLC. 3/F, Building 2, Dongguan Hi-Tech Park, 288# Qiuyi Road, Binjiang District, Hangzhou, Zhejiang, China
Country 79855 0
China
Phone 79855 0
+86 0571 87563327
Fax 79855 0
Email 79855 0
jgu@gmaxbiopharm.com
Contact person for scientific queries
Name 79856 0
Mr Yong Guo
Address 79856 0
Gmax Biopharm, LLC. 3/F, Building 2, Dongguan Hi-Tech Park, 288# Qiuyi Road, Binjiang District, Hangzhou, Zhejiang, China
Country 79856 0
China
Phone 79856 0
+86 0571 8663 3937
Fax 79856 0
Email 79856 0
yguo@gmaxbiopharm.com

No data has been provided for results reporting
Summary results
Not applicable