Clinical trial NCT02284009: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
Official title: Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: New-onset type 1 diabetes mellitus
Albiglutide
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-11-05
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: 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
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64
timeFrame: Baseline and Weeks 16, 28 and 64
measure: Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64
timeFrame: Baseline and Weeks 16, 28, 52 and 64
measure: Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64
timeFrame: Baseline and Weeks 16, 28, 52 and 64
measure: Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64
timeFrame: Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
measure: 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
timeFrame: Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
measure: Change From Baseline in Percent HbA1c at Week 52
timeFrame: Baseline and Week 52
measure: Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64)
timeFrame: Weeks 4, 8, 16, 28, 40, 52 and 64
measure: Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64
timeFrame: Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
measure: Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52
timeFrame: Week 24 to 52
measure: 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
timeFrame: Baseline and Weeks 28 and 52
measure: Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
timeFrame: Baseline and Weeks 28 and 52
measure: Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
timeFrame: Baseline and Weeks 28 and 52
measure: Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
timeFrame: Baseline and Weeks 28 and 52
measure: Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
timeFrame: Baseline and weeks 28 and 52
measure: Change From Baseline in Body Weight (Kilograms) at Week 52
timeFrame: Baseline and Week 52
measure: Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
timeFrame: Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64
measure: Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F]
timeFrame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
measure: Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F]
timeFrame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
measure: Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka]
timeFrame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Other outcomes:
Locations:
city: Bois-Guillaume
country: France
facility: GSK Investigational Site
city: Caen Cedex 9
country: France
facility: GSK Investigational Site
city: Lille Cedex
country: France
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Latina
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Roma
country: Italy
facility: GSK Investigational Site
city: Alzira/Valencia
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: GSK Investigational Site
city: Lleida
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Málaga
country: Spain
facility: GSK Investigational Site
city: Pama de Mallorca
country: Spain
facility: GSK Investigational Site
city: San Juan (Alicante)
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: Darlington
country: United Kingdom
facility: GSK Investigational Site
city: Dundee
country: United Kingdom
facility: GSK Investigational Site
city: Durham
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Pozzilli P, Bosi E, Cirkel D, Harris J, Leech N, Tinahones FJ, Vantyghem MC, Vlasakakis G, Ziegler AG, Janmohamed S. Randomized 52-week Phase 2 Trial of Albiglutide Versus Placebo in Adult Patients With Newly Diagnosed Type 1 Diabetes. J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgaa149. doi: 10.1210/clinem/dgaa149.