Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus

Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus

Sponsors

Lead sponsor: GlaxoSmithKline

Source GlaxoSmithKline
Brief Summary

This is a Phase II, randomized, double-blind, parallel group, placebo controlled, multicentre study of 52 weeks treatment duration. The primary objective is to evaluate the efficacy(on endogenous insulin secretion), safety and tolerability of weekly albiglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist) versus placebo when added to insulin therapy in subjects with new-onset type 1 diabetes mellitus (NOT1DM) and residual insulin production.. Approximately 68 eligible subjects will be randomised in a 3:1 ratio such that 51 subjects receive albiglutide 30 milligram (mg) once weekly (with increase to 50 mg once weekly at Week 6 if the 30-mg weekly dose is tolerated) added-on to insulin therapy and 17 subjects receive placebo once weekly added-on to insulin therapy. The total duration of a subject's participation will be approximately 72 weeks (up to 8 weeks of Screening, 52 weeks of treatment and 12 weeks of Post-treatment Follow-up)

Overall Status Completed
Start Date October 10, 2014
Completion Date October 18, 2017
Primary Completion Date October 18, 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean Change From Baseline in Time Normalized Stimulated (From Mixed Meal Tolerance Test [MMTT]) 2-hour Plasma C-peptide Area Under the Curve (AUC) at Week 52 Baseline and Week 52
Secondary Outcome
Measure Time Frame
Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64 Baseline and Weeks 16, 28 and 64
Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64 Baseline and Weeks 16, 28, 52 and 64
Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64 Baseline and Weeks 16, 28, 52 and 64
Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64 Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Percentage of Participants Achieving Partial Remission Status (Insulin Dose-adjusted Hemoglobin A1c (IDAA1C)<= 9.0) at Baseline, Week 4, 8, 16, 28, 40, 52 and 64 Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Change From Baseline in Percent HbA1c at Week 52 Baseline and Week 52
Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64) Weeks 4, 8, 16, 28, 40, 52 and 64
Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64 Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52 Week 24 to 52
Time Spent With Plasma Glucose Level <= 3.9, > 3.9 to <= 10.0, and > 10.0 Measured by 72 Hour Continuous Glucose Monitoring (CGM) at Baseline, Week 28 and 52 Baseline and Weeks 28 and 52
Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 Baseline and Weeks 28 and 52
Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 Baseline and Weeks 28 and 52
Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 Baseline and Weeks 28 and 52
Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 Baseline and weeks 28 and 52
Change From Baseline in Body Weight (Kilograms) at Week 52 Baseline and Week 52
Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64) Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64
Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F] 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F] 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka] 48 hours after the most recent dose at Week 4, 6, 8 and 16
Enrollment 67
Condition
Intervention

Intervention type: Biological

Intervention name: Albiglutide weekly injection

Description: Albiglutide will be provided as a fixed-dose, fully disposable pen injector system having a prefilled dual chamber glass cartridge. To be self-administered as a subcutaneous (SC) injection in the abdomen, thigh or upper arm region. The pen will deliver either 30 mg of albiglutide, 50 mg of albiglutide in a 0.5-mL injection volume. It may be administered at any time of day without regard to meals. It will be administered once a week on the same day each week

Arm group label: Albiglutide

Intervention type: Biological

Intervention name: Placebo weekly injection

Description: Placebo provided as a fixed-dose, fully disposable pen injector system having a prefilled dual chamber glass cartridge. To be self-administered as a SC injection in the abdomen, thigh or upper arm region. It may be administered at any time of day, once a week on the same day each week, without regard to meals.

Arm group label: Placebo

Intervention type: Biological

Intervention name: Insulin

Description: Commercially available basal/bolus insulin regimen, self administered by the subject, in accordance to the prescription of the physician and as per the package insert

Eligibility

Criteria:

Inclusion Criteria:

- Male or female, aged 18 to 30 years, inclusive, with a diagnosis of T1DM with an interval of 28-56 days between the initial diagnosis and the first dose of study drug. Documentation of the diagnosis of T1DM (and not just insulin deficiency), including the date of diagnosis, must be obtained from the diagnosing physician.

- Currently requires insulin for T1DM treatment, or has required insulin therapy for T1DM (for >=7 days) between the date of diagnosis and the first dose of study drug. Note: subjects currently taking twice daily commercially available pre-mixed insulin will not be eligible.

- Positive for at least one of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD) antibody to protein tyrosine phosphatase-like protein (anti-IA-2) or an insulin autoantibody (IAA). Please note: A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has been using insulin for a total of >=7days.

- Evidence of residual functioning pancreatic beta-cells as measured by a peak stimulated C-peptide level > 0.20 nanomoles/litres (nmol/L) during the Screening MMTT when plasma glucose level is >3.9 mmol/L (70 mg/dL) and <=11.1 mmol/L (200 mg/dL). Note: the Screening MMTT should not be performed within one week of resolution of a DKA event.

- Body mass index <=32.0 kilogram/square meters (kg/m^2).

- Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (i.e., meeting one of the criteria defined below) from at least 14 days prior to the first dose of randomised study medication until the 12-week post-treatment Follow-up visit : Abstinence from penile-vaginal intercourse, when this is the female's preferred and usual lifestyle; Oral Contraceptive, either combined or progestogen alone ; Injectable progestogen; Implants of etonogestrel or levonorgestrel; Estrogenic vaginal ring; Percutaneous contraceptive patches; Intrauterine device or intrauterine system that has a failure rate of less than 1% per year when used consistently and correctly as stated in the product label; Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the site personnel's review of subject's medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history.; Male condom combined with a female diaphragm, either with or without a vaginal spermicide

- Able and willing to provide written informed consent and to comply with all study procedures.

Exclusion Criteria:

- Severe gastroparesis i.e., requiring therapy within 6 months prior to Screening

- History of acute or chronic pancreatitis, or considered clinically at significant risk of developing pancreatitis, during the course of the study (e.g. due to symptomatic gallstones, excess alcohol use).

- History of significant gastrointestinal surgery that in the opinion of the investigator is likely to significantly affect upper gastrointestinal or pancreatic function (e.g. gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function)

- Personal history or family history of thyroid medullary carcinoma or multiple endocrine neoplasia type 2 (MEN2)

- History of cancer that has not been in full remission for at least 3 years before Screening. (A history of squamous cell or basal cell carcinoma of the skin, or treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)

- Fasting triglyceride level >750 milligram/decilitre (mg/dL) at Screening. Subjects may be re-tested once during screening, and if the value no longer meets the exclusion criterion, the subject can be randomly assigned to treatment

- Estimated Glomerular Filtration Rate (eGFR) <=30 mL/min/1.73 m^2 (calculated using the Modification of Diet in Renal Disease (MDRD) formula

- Haemoglobinopathy that may affect proper interpretation of HbA1c

- Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) and bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). [Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria and are not on active antiviral treatment (e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening)]

- Any clinically significant co-morbidity or abnormality (including psychiatric disorder, any other autoimmune endocrinopathy e.g., primary autoimmune hypothyroidism, hyperadrenalism, coeliac disease etc) that in the opinion of the Investigator, may pose additional risk in administering study medication or trial participation

- Female subject is pregnant (confirmed by laboratory testing) or lactating

- Known allergy to any GLP-1 analogue, insulin, or excipients of albiglutide

- Treatment with any oral anti-diabetic medication within the prior 30 days or 5 half lives of that medication, whichever is longer.

- Use of immunosuppressants, intravenous immunoglobulin, oral or systemically injected glucocorticoids within the 3 months before randomisation or high likelihood of a requirement for prolonged treatment (>1 week) in the year following randomisation. However, short courses of oral steroids (single dose or multiple doses for up to 7 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, and small quantities of non-potent topical corticosteroids are allowed

- Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is longer, before Screening, a history of receipt of an investigational anti-diabetic drug within the 3 months before randomisation, or receipt of albiglutide in previous studies.

Gender: All

Minimum age: 18 Years

Maximum age: 30 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
GSK Clinical Trials Study Director GlaxoSmithKline
Location
facility
GSK Investigational Site | Bois-Guillaume, 76230, France
GSK Investigational Site | Caen Cedex 9, 14033, France
GSK Investigational Site | Lille Cedex, 59037, France
GSK Investigational Site | Muenchen, Bayern, 80804, Germany
GSK Investigational Site | Frankfurt, Hessen, 60590, Germany
GSK Investigational Site | Duesseldorf, Nordrhein-Westfalen, 40225, Germany
GSK Investigational Site | Dresden, Sachsen, 01307, Germany
GSK Investigational Site | Latina, Lazio, 04100, Italy
GSK Investigational Site | Milano, Lombardia, 20132, Italy
GSK Investigational Site | Roma, 00128, Italy
GSK Investigational Site | Alzira/Valencia, 46600, Spain
GSK Investigational Site | Badalona, 08916, Spain
GSK Investigational Site | Barcelona, 08036, Spain
GSK Investigational Site | Granada, 18012, Spain
GSK Investigational Site | Hospitalet de Llobregat, 08907, Spain
GSK Investigational Site | Lleida, 25198, Spain
GSK Investigational Site | Madrid, 28006, Spain
GSK Investigational Site | Málaga, 29010, Spain
GSK Investigational Site | Pama de Mallorca, 07010, Spain
GSK Investigational Site | San Juan (Alicante), 03550, Spain
GSK Investigational Site | Sevilla, 41014, Spain
GSK Investigational Site | Birmingham, B9 5SS, United Kingdom
GSK Investigational Site | Bristol, BS2 8HW, United Kingdom
GSK Investigational Site | Cardiff, CF14 4XN, United Kingdom
GSK Investigational Site | Darlington, DL3 6HX, United Kingdom
GSK Investigational Site | Dundee, DD1 9SY, United Kingdom
GSK Investigational Site | Durham, DH1 5TW, United Kingdom
GSK Investigational Site | Glasgow, G31 2ER, United Kingdom
GSK Investigational Site | Liverpool, L7 8XP, United Kingdom
GSK Investigational Site | London, E1 2AT, United Kingdom
GSK Investigational Site | Newcastle upon Tyne, NE1 4LP, United Kingdom
GSK Investigational Site | Sheffield, S5 7AU, United Kingdom
Location Countries

France

Germany

Italy

Spain

United Kingdom

Verification Date

March 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Albiglutide

Arm group type: Experimental

Description: Approximately 51 subjects will be assigned to albiglutide 30 mg weekly (with treatment-masked increase to 50 mg weekly at Week 6) + background insulin. The starting dose of albiglutide will be 30 mg once weekly and will be increased at Week 6 to 50 mg, once weekly, if the 30-mg weekly dose is tolerated.

Arm group label: Placebo

Arm group type: Experimental

Description: Approximately 17 subjects will be assigned to albiglutide matching placebo + background insulin

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov