Phase 2
N=67
Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
Diabetes Mellitus, Type 1
Bottom Line
View on ClinicalTrials.gov: NCT02284009 ↗Enrolled (actual)
67
Serious AEs
4.5%
Results posted
Mar 2019
Primary outcome: Primary: 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 — -0.16; -0.13; -0.27 Nanomoles per liter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Albiglutide weekly injection (Biological); Placebo weekly injection (Biological); Insulin (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Oct 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
-0.16; -0.13; -0.27 | — |
| SECONDARY Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64 |
0.00; 0.07; -0.14; 0.01; -0.22; -0.22 | — |
| SECONDARY Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64 |
0.86; 0.82; 0.84; 1.02; 0.68; 0.91 | — |
| SECONDARY Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64 |
-2.28; -1.10; -2.97; 3.91; -0.31; 4.66 | — |
| SECONDARY Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64 |
26.7; 37.0; 71.4; 78.6; 85.7; 67.4 | — |
| SECONDARY 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 |
73.3; 60.9; 92.9; 88.1; 92.9; 87.0 | — |
| SECONDARY Change From Baseline in Percent HbA1c at Week 52 |
-0.73; -0.59 | — |
| SECONDARY Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64) |
6.29; 6.10; 5.91; 5.82; 5.97; 5.78 | — |
| SECONDARY Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64 |
-0.02; -0.03; -0.04; -0.02; -0.05; -0.01 | — |
| SECONDARY Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52 |
472; 1592; 0; 0; 241; 996 | — |
| SECONDARY 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 |
0.80; 0.98; 1.72; 1.38; 1.60; 1.36 | — |
| SECONDARY Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 |
0.40; 0.36; 0.31; 0.28; 0.25; 0.40 | — |
| SECONDARY Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 |
0.24; 0.22; 0.18; 0.08; 0.22; 0.17 | — |
| SECONDARY Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 |
0.80; 1.53; 1.23; 0.73; 1.17; 1.30 | — |
| SECONDARY Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52 |
0.94; 2.72; 2.05; 1.52; 2.19; 2.42 | — |
| SECONDARY Change From Baseline in Body Weight (Kilograms) at Week 52 |
0.26; 0.77 | — |
| SECONDARY Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64) |
70.16; 66.16; 69.87; 66.39; 69.83; 65.65 | — |
| SECONDARY Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F] |
45.1 | — |
| SECONDARY Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F] |
4830 | — |
| SECONDARY Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka] |
0.0122 | — |
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)
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 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) 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 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.
Data sourced from ClinicalTrials.gov (NCT02284009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.