Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000839000
Ethics application status
Approved
Date submitted
4/10/2010
Date registered
6/10/2010
Date last updated
1/02/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, single dose, dose-ascending study of VRS-859, to observe the safety, tolerability and effect in Patients with Type 2 Diabetes Mellitus
Scientific title
A Placebo Controlled Single Ascending Dose Phase 1 study for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Subcutaneous Administration of VRS-859 in Patients with Type 2 Diabetes Mellitus
Secondary ID [1] 252817 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 258326 0
Condition category
Condition code
Metabolic and Endocrine 258512 258512 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The drug being studied is called VRS-859, and it is administered subcutaneously (into tissue under the skin).
It is being studied for its effectiveness in the treatment of Type 2 Diabetes Mellitus.
a) There are 5 potential dose groups (12.5mg, 25mg, 50mg, 100mg and 150mg) of VRS-859. There is also a placebo (a simulated medical intervention) that patients may receive.
b) Patients will be assessed in groups of 11, beginning with the lowest dose of VRS-859 or placebo.
c) Doses will be administered once only. Patients will receive either one, two or three injections depending on the cohort.
d) Each patient will be monitored at regular intervals for a period of 30 days after treatment and then followed-up 60 days after treatment.

Only 1 dose group will be dosed at a time, once safety and tolerability are assessed for that group and it is deemed safe to continue, the next dose group will be dosed.
Intervention code [1] 257340 0
Treatment: Drugs
Comparator / control treatment
Each patient that enters will have roughly a 28% percent chance of receiving non-active drug (placebo). The active drug will be administered in the same fashion as the placebo to maintain blinding. The placebo will be composed of normal saline (0.9% w/v Sodium Chloride-NaCl) and 20 mm L-Histidine (0.154M2) at pH 5.5. The placebo will be dosed as a single administration (may be more than one injection), as per VRS-859.
All follow-up assessments and patient monitoring will be identical to that of patients who receive VRS-859.
Control group
Placebo

Outcomes
Primary outcome [1] 259348 0
Primary Outcome 1: To determine the safety and tolerability of a single dose of VRS-859 in Type 2 Diabetes Mellitus patients.
Timepoint [1] 259348 0
Timepoint 1: VRS-859 is administered as a single dose on Day 1. Safety and tolerability will be regularly assessed with the patient confined to the site for 48 hrs after administration. Out-patient follow-up visits will then be performed on Days 4, 8, 11, 15, 18, 22, 25 and 30. A follow-up visit will then take place at Day 60 after study drug is administered.
Safety and Tolerability will be measured by vital signs, an electrocardiogram (ECG), a physical exam, blood and urine tests performed through-out all visits.
Secondary outcome [1] 265814 0
Secondary Outcome 1: To determine the single dose pharmacokinetics of VRS-859 administered subcutaneous(SC) in patients with Type 2 diabetes mellitus.
Timepoint [1] 265814 0
Timepoint 1: Pharmacokinetics and pharmacodynamics will be assessed via blood samples taken at multiple times throughout the study (Pre dose: 24 and 2 hrs; Post dose: 30mins, 1hr, 2hr, 4hr, 8hr, 12hr, 24hr, 36hr, 48hr and Days: 4, 8, 11, 15, 18, 22, 25 and 30).
Secondary outcome [2] 265815 0
Secondary Outcome 2: To assess the activity of VRS-859 by measurement of fasting plasma glucose (FPG) and response to oral Glucose Tolerance Test (GTT) at selected times post-dose in patients with Type 2 diabetes mellitus.
Timepoint [2] 265815 0
Timepoint 2: Glucose Tolerance Test (GTT) will be assessed via blood samples taken multiple times throughout the study (Pre dose and at 15min intervals post-dose for 2 hours)
Secondary outcome [3] 265816 0
Secondary Outcome 3: To evaluate post-Glucose Tolerance Test (GTT) glucose excursions following administration of a single SC dose of VRS-859.
Timepoint [3] 265816 0
Timepoint 3: Glucose Tolerance Test (GTT) will be assessed via blood samples taken multiple times throughout the study (Pre dose and at 15min intervals post-dose for 2 hours)

Eligibility
Key inclusion criteria
1. Age 21 to 62 years
2. Body Mass Index (BMI) between 25 and 40 kg/m2 inclusive and a minimum body weight of 50 kg
3. Negative serum pregnancy test for females of childbearing potential
4. Diagnosis of Type 2 diabetes at least 6 months prior to dosing as documented in the patient’s medical history
5. Fasting plasma glucose level (inclusive) of 130-260 mg/dL (7.22 – 14.44 mM inclusive) AND glycosylated hemoglobin (HbA1c) range (inclusive) of 7 – 10.5% for patients on metformin alone or 6.5-10% for patients on metformin and sulfonylurea [Patients on sulfonylurea will stop taking it for 2 weeks prior to dosing and will receive metformin during study]
6. Diet and exercise program and on a fixed dose of oral diabetic agent (metformin alone or metformin and sulfonylurea) for at least 3 months prior to enrollment
7. Willing and able to give informed consent
8. QT correction (QTc) value of less than 450 msec by ECG
Minimum age
21 Years
Maximum age
62 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have received treatment for any bacterial, viral or fungal infection within 30 days of prior to study drug dosing
2. Any oral antidiabetic monotherapy (except metformin or sulfonylurea) within 3 months prior to enrollment
3. Currently taking or have been on treatment with thiazolidinedione (TZD) within the past 3 months
4. Pancreatitis within 5 yrs prior to enrollment
5. Documented history of or current significant cardiovascular, cerebrovascular, renal or hepatobillary disease
6. Pancreatic enzymes (amylase, lipase) outside laboratory normal range
7. Fasting serum triglycerides > 500 mg/dL (5.6 mmol/L)
8. Use of gastric motility drugs within one week prior to study enrollment
9. Positive drugs screen and alcohol breath test at screening or at admission
10. Positive serology for Hepatitis B (HBV), Hepatitis C (HCV), or Human Immunodeficiency Virus (HIV). Must also have no prior history of HBV or HCV virus infection
11. Prior history of cancer excluding adequately treated basal cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix
12. Women who are pregnant or breastfeeding
13. Unwilling to use two effective birth control methods while on study
14. Unwilling to abstain from recreational drug use
15. Unwilling to refrain from alcohol use at least 48 hours prior to screening and enrollment.
16. Any prior treatment with glucagon-like peptide-1 (GLP-1) analog (e.g. Byetta, Victoza)
17. Treatment on dipeptidyl peptidase IV (DPP IV) inhibitor within 3 months prior to screening
18. Treatment with an investigational drug within past 30 days prior to screening
19. Treatment with insulin within the past 3 months prior to screening

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)
Eligible patients will already have been diagnosed with Type 2 Diabetes Mellitus. Providing patients meet most of the eligibility criteria, the site principal study doctor or delegate will approach them regarding the study.
Patients will be given information and the informed consent form and will be asked to take this home and discuss it with whoever they choose. If patients are happy to participate, they will be brought back to see the principal study doctor who will sign the consent form with them, and then the patient can be screened.
The site staff will log in to an interactive web response system called IWRS. The patient who will be screened will be entered into the system (date of birth, gender, initials). This IWRS system will randomly assign them (like flipping a coin) to a cohort (treatment group) and will also assign them a study number.
This information will be emailed to the site staff that logged the call. This IWRS system will also allocate the specified drug vials to be administered to the patient. The site staff will not know whether active drug or placebo is being given, they will however know which vials to select for treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The site will know which dose level the patient will receive, though not study drug versus placebo.
Once all screening procedures have been completed and results obtained, the information is put into an automated system which will assign the patient a number and will randomly assign them (like flipping a coin) to treatment or placebo.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/10/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 2949 0
Switzerland
State/province [1] 2949 0
Country [2] 2950 0
United Kingdom
State/province [2] 2950 0

Funding & Sponsors
Funding source category [1] 257795 0
Commercial sector/Industry
Name [1] 257795 0
Versartis Inc.
Country [1] 257795 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Versartis Inc.
Address
500 Ellis Street
Mountain View, CA 94043
Country
United States of America
Secondary sponsor category [1] 256998 0
Commercial sector/Industry
Name [1] 256998 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 256998 0
Level 4, 88 Jephson Street Toowong, Brisbane, QLD 4066
Country [1] 256998 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259820 0
Bellberry Limited
Ethics committee address [1] 259820 0
229 Greenhill Road, Dulwich SA 5065
Ethics committee country [1] 259820 0
Australia
Date submitted for ethics approval [1] 259820 0
11/08/2010
Approval date [1] 259820 0
Ethics approval number [1] 259820 0

Summary
Brief summary
This will be the first time VRS-859 will be administered to humans. The principal aim of this study is to obtain safety and tolerability data from type 2 diabetic patients administered a subcutaneous dose of VRS-859. The study will also provide data on the single dose pharmacokinetics. Assessment of the activity of VRS-859 will be measured by testing fasting plasma glucose (FPG) and response to oral GTTs at selected times post-dose. This combined data will help establish the best dose and optimum dosage regimen for administration to patients.
The study design provides an opportunity to evaluate the potential of VRS-859 to be administered monthly to patients that are already on a diet and exercise program with a well established standard of care, metformin. Interim safety assessments of each treatment group (cohort dose) will be made prior to escalating to the next higher dose thus providing additional opportunity to evaluate the overall safety of each dose and to define the safest monthly dose.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31734 0
Address 31734 0
Country 31734 0
Phone 31734 0
Fax 31734 0
Email 31734 0
Contact person for public queries
Name 14981 0
Clinical Enquiries
Address 14981 0
Level 4, 88 Jephson St
Toowong, QLD 4066
Australia
Country 14981 0
Australia
Phone 14981 0
+61 (0)7 3719 6000
Fax 14981 0
+61 (0)7 3719 6011
Email 14981 0
cns@clinical.net.au
Contact person for scientific queries
Name 5909 0
Clinical Enquiries
Address 5909 0
Level 4, 88 Jephson St
Toowong, QLD 4066
Australia
Country 5909 0
Australia
Phone 5909 0
+61 (0)7 3719 6000
Fax 5909 0
+61 (0)7 3719 6011
Email 5909 0
cns@clinical.net.au

No information has been provided regarding IPD availability


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
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