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

NCT02284009 | Completed Phase 2 Results

• 1 other identifier: 110933
• Study Type: interventional
• Target: 67
• Locations: 5 countries
• Sites: 32

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)

Conditions

Diabetes Mellitus, Type 1

Keywords

New-onset type 1 diabetes mellitus; Albiglutide

Outcome Measures

Primary Outcomes (1)

• 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

  Participants (parts) had a balanced diet consistent with dietitian's advice and made no major changes in exercise regimens. Evening before the MMTT, participants had a full meal then fasted from 9 post meridiem (pm) until MMTT was completed. Water, black coffee or tea without sugar or artificial sweeteners was allowed. Plasma glucose was measured prior to the finger-stick test and MMTT was performed only if in range \> 3.9 millimoles per liter (mmol/L) \[70 mg/deciliter (dL)\] and \<= 11.1 mmol/L (200 mg/dL). Baseline was defined as the last non-missing value with assessment date on or before the 1st day of study medication. Change from Baseline was calculated by subtracting Baseline value from Week 52 value. Intent-to-treat (ITT) Population comprised of all randomly assigned participants who received at least 1 dose of study medication with at least 1 post-Baseline assessment of the primary endpoint.

  Baseline and Week 52

Secondary Outcomes (19)

• 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

Study Arms (2)

Albiglutide

EXPERIMENTAL

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.

Biological: Albiglutide weekly injection; Biological: Insulin

Placebo

EXPERIMENTAL

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

Biological: Placebo weekly injection; Biological: Insulin

Interventions

Albiglutide weekly injection BIOLOGICAL

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

Albiglutide

Placebo weekly injection BIOLOGICAL

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.

Placebo

Insulin BIOLOGICAL

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

Albiglutide; Placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (32)

GSK Investigational Site

Bois-Guillaume, 76230, France

Location

GSK Investigational Site

Caen, 14033, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Munich, Bavaria, 80804, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01307, Germany

Location

GSK Investigational Site

Latina, Lazio, 04100, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Roma, 00128, Italy

Location

GSK Investigational Site

Alzira/Valencia, 46600, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Granada, 18012, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Lleida, 25198, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Pama de Mallorca, 07010, Spain

Location

GSK Investigational Site

San Juan (Alicante), 03550, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

Bristol, BS2 8HW, United Kingdom

Location

GSK Investigational Site

Cardiff, CF14 4XN, United Kingdom

Location

GSK Investigational Site

Darlington, DL3 6HX, United Kingdom

Location

GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

GSK Investigational Site

Durham, DH1 5TW, United Kingdom

Location

GSK Investigational Site

Glasgow, G31 2ER, United Kingdom

Location

GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

Location

GSK Investigational Site

London, E1 2AT, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

GSK Investigational Site

Sheffield, S5 7AU, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32219329 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: November 5, 2014
• Study Start: October 10, 2014
• Primary Completion: October 18, 2017
• Study Completion: October 18, 2017
• Last Updated: June 29, 2020
• Results First Posted: March 25, 2019

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (11); FR (3); IT (3); DE (4); ES (11)