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Trial registered on ANZCTR


Registration number
ACTRN12617000811303
Ethics application status
Approved
Date submitted
23/05/2017
Date registered
2/06/2017
Date last updated
17/10/2019
Date data sharing statement initially provided
17/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Placebo-controlled, Double-blind, Semi-sequential Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Escalating Subcutaneous Doses of Glutazumab in Subjects with Type 2 Diabetes
Scientific title
A Randomised, Placebo-controlled, Double-blind, Semi-sequential Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Escalating Subcutaneous Doses of Glutazumab in Subjects with Type 2 Diabetes
Secondary ID [1] 292022 0
Gmax_GLUT_MAD_01
Universal Trial Number (UTN)
U1111-1196-7846
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes (T2D) 303409 0
Condition category
Condition code
Metabolic and Endocrine 302820 302820 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be a multi-centre, double-blind, semi-sequential group, placebo-controlled, doseescalation study to assess the safety, tolerability and PK/PD of glutazumab in subjects with T2D.
Four sequential cohorts, each with 6 subjects receiving glutazumab and 2 subjects receiving placebo, will be given increasing doses of glutazumab once weekly for 8 weeks (8 SC injections). The doses administered will be 5, 10, 20, and 30 mg once weekly. Prior to each dose escalation a Safety Review Committee (SRC) will meet to confirm the next dose level. A next dose level can only be started when all subjects in the preceding dose level have completed 4 weeks of dosing. Based on safety and PK data of these subjects a fifth cohort will be treated with a dose of glutazumab that will be determined by the SRC to be the most promising based on a risk-benefit evaluation.
After Screening, subjects will undergo a 4-week single-blind run-in period. All background diabetes medication will be kept constant. At the end of the single-blind run-in period, subjects will be randomised 3:1 to receive either glutazumab or placebo, and the 8-week double-blind treatment period will begin.
During the study, subjects will be reimbursed for their meals, parking during their visits, and investigator and research nurses will keep in close contact with subjects by weekly phone call and regular email to ensure the adherence to the study .
Intervention code [1] 298150 0
Treatment: Drugs
Comparator / control treatment
Placebo, containing the same constituents and excipients as Glutazumab Injection, apart from the active component (Glutazumab).
Control group
Placebo

Outcomes
Primary outcome [1] 302324 0
Glycaemic control assessed by change from baseline in Fasting Blood Glucose
Timepoint [1] 302324 0
baseline, and at 4 and 8 weeks after intervention commencement.
Primary outcome [2] 302325 0
Glycaemic control assessed by change from baseline in HbA1c
Timepoint [2] 302325 0
baseline, and at 4 and 8 weeks after intervention commencement.
Primary outcome [3] 302326 0
Change frome baseline in body weight.
Timepoint [3] 302326 0
baseline, and at 4 and 8 weeks after intervention commencement.
Secondary outcome [1] 335161 0
Change from Baseline in mixed-meal tolerance test (MMTT) AUC Blood Glucose from 0 to 2 h (AUCBG,0-2 h)
Timepoint [1] 335161 0
week 4 and 8.
Secondary outcome [2] 335162 0
% of subjects whose HbA1c tested lower than 7% by serum assay.
Timepoint [2] 335162 0
week 4 and 8
Secondary outcome [3] 335163 0
Change from Baseline in self-monitored blood glucose (SMBG).
Timepoint [3] 335163 0
Week 2, 4, 6, and 8
Secondary outcome [4] 335164 0
Change from Baseline in pancreatic beta-cell function (C-peptide) by serum assay.
Timepoint [4] 335164 0
week 4 and 8.
Secondary outcome [5] 335165 0
Change from Baseline in blood pressure.
Timepoint [5] 335165 0
week 4 and 8.
Secondary outcome [6] 335166 0
PK paremeters, t1/2, Cmax, Tmax. by serum assay.
Timepoint [6] 335166 0
pre-dose, 4, 8, 24, 48, 72, 96 and 168 hours post injection in week 1; pre-dose in week 2, 3, 4, 5 and 6; pre-dose , 4, 8, 24, 48, 72, 96, 168, 336 and 504 hours post injection in week 7, week 8, week 9 and week 10.
Secondary outcome [7] 335167 0
adverse events (AEs) including hypoglycaemia, hypersensitivity reactions, injection site reactions, pancreatitis, and thyroid malignancies will be assessed by physical examinations, vital signs measurements, clinical laboratory tests, urinalysis, 12-lead ECG, routine clinical observations, immunogenicity (anti-drug antibodies), use of rescue medication, and monitoring of adverse events (AEs) / AEs of special interest (AESIs).
Timepoint [7] 335167 0
Baseline through 13 weeks

Eligibility
Key inclusion criteria
-Type 2 Diabetes diagnosed >6 months ago and controlled with diet or exercise alone or on stable doses of 1 or 2 of the following classes of OAMs:
Metformin; Sulfonylureas;Glinides; Thiazolidinediones; Acarbose.
-If more than 2 of the permitted OAMs listed above are taken at Screening a wash-out period of 3 weeks will be needed.
- Body Mass Index (BMI) greater than or equal to 27 kg/m squared2 and less than or equal to 40 kg/m squared2
- Glycated haemoglobin (HbA1c) greater than or equal to 6.5% and less than or equal to 10.5%
- Fasting C-peptide greater than or equal to 0.8 ng/mL (greater than or equal to 0.26 nmol/L)
-Lipids, untreated or controlled with lipid-lowering drugs:
a. Total cholesterol less than 200 mg/dL
b. Low-density lipoprotein less than 100 mg/dL
c. Fasting triglyceride level less than 400 mg/dL
- Females must be non-lactating
-Females or female partners of male study subjects must be surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, have a negative urine pregnancy test at Screening and be willing to practice sexual abstinence or use an accepted form of contraception with her partner during treatment and for at least 30 days following the last dose of study drug.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Type 1 diabetes
- Any insulin use within 30 days prior to Screening or less than 7 days of consecutive insulin use in the 3 months prior to Screening
-Clinically significant cardiovascular and/or cerebrovascular diseases including, but not limited to stroke or transient ischemic attack, Active, unstable coronary heart disease, Unstable angina etc.
-Clinically significant laboratory abnormalities, including but not limited to Bilirubin, Aspartate aminotransferase (AST), glomerular filtration rate, etc.
- Lipase and amylase at Screening > upper limit of normal (ULN)
- History of acute or chronic liver disease
- Positive hepatitis B surface antigen or positive hepatitis C virus testing or positive for HIV
- Currently ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.
- Poorly controlled hyperthyroidism (thyroid-stimulating hormone greater than 2 times ULN).
- Use of any GLP-1 analogue and/or DPP4 inhibitor within the last 30 days.
- Significant allergies to humanised monoclonal antibodies or allergies to other components of the study medication
- Females who are pregnant or breast-feeding and subjects of both sexes of childbearing potential who are not willing to use adequate contraceptive methods.

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)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation is Concealed, computerised sequence generation
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
The people analysing the results/data
Intervention assignment
Other
Other design features
Subjects allocated in each cohort will be randomised 3:1 to receive either glutazumab or placebo.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The summary tables of AEs will present the number and percentage of subjects and the number of events. All other safety data will be summarised at each protocol scheduled time point.
Change from Baseline of pharmacodynamics parameters will be analysed using the analysis of covariance procedure adjusting for Baseline values.
Plasma concentration will be used to calculate the PK parameters.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2017
Actual
30/10/2017
Date of last participant enrolment
Anticipated
22/10/2019
Actual
Date of last data collection
Anticipated
30/04/2020
Actual
Sample size
Target
44
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 8082 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 8083 0
Linear Clinical Research - Nedlands
Recruitment hospital [3] 8084 0
The Wesley Hospital - Auchenflower
Recruitment hospital [4] 10543 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 16136 0
5000 - Adelaide
Recruitment postcode(s) [2] 16137 0
6009 - Nedlands
Recruitment postcode(s) [3] 16138 0
4066 - Auchenflower
Recruitment postcode(s) [4] 22262 0
2031 - Randwick
Recruitment outside Australia
Country [1] 8915 0
New Zealand
State/province [1] 8915 0

Funding & Sponsors
Funding source category [1] 296553 0
Commercial sector/Industry
Name [1] 296553 0
Gmax Biopharm Australia Pty Ltd
Country [1] 296553 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gmax Biopharm Australia Pty Ltd
Address
61/41 Rocklands Road
Wollstonecraft, NSW 2065 Australia
Country
Australia
Secondary sponsor category [1] 295503 0
None
Name [1] 295503 0
Address [1] 295503 0
Country [1] 295503 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297767 0
Bellberry Ethics Committee
Ethics committee address [1] 297767 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 297767 0
Australia
Date submitted for ethics approval [1] 297767 0
05/04/2017
Approval date [1] 297767 0
07/08/2017
Ethics approval number [1] 297767 0
Ethics committee name [2] 300050 0
Health and Disability Ethics Committees
Ethics committee address [2] 300050 0
133 Molesworth Street, PO Box 5013, Wellington, New Zealand, 6011
Ethics committee country [2] 300050 0
New Zealand
Date submitted for ethics approval [2] 300050 0
24/05/2017
Approval date [2] 300050 0
09/08/2017
Ethics approval number [2] 300050 0

Summary
Brief summary
This study will be a multi-centre, double-blind, semi-sequential group, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK/PD of glutazumab in subjects with T2D.
After Screening, subjects will undergo a 4-week single-blind run-in period. All background diabetes medication will be kept constant. At the end of the single-blind run-in period, subjects will be randomised 3:1 to receive either glutazumab or placebo, and the 8-week double-blind treatment period will begin.
Glycaemic control, Change frome baseline in body weight, Adverse events of special interest(AESIs) will be assessed. Pharmacodynamics and pharmacokinetics results will be collected.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75054 0
Dr Sepehr Shakib
Address 75054 0
Cmax, 18a North Terrace, Level 5, Adelaide, SA AUS 5000 Australia
Country 75054 0
Australia
Phone 75054 0
+61 8 8222 2763
Fax 75054 0
Email 75054 0
[email protected]
Contact person for public queries
Name 75055 0
Mr Yong Guo
Address 75055 0
Gmax Biopharm Australia Pty Ltd ,61/41 Rocklands Road, Wollstonecraft NSW 2065,Australia
Country 75055 0
Australia
Phone 75055 0
+86 177 6707 5321
Fax 75055 0
Email 75055 0
[email protected]
Contact person for scientific queries
Name 75056 0
Mr Yong Guo
Address 75056 0
Gmax Biopharm Australia Pty Ltd, 61/41 Rocklands Road, Wollstonecraft NSW 2065,Australia
Country 75056 0
Australia
Phone 75056 0
+86 177 6707 5321
Fax 75056 0
Email 75056 0
[email protected]

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


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.