Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Albiglutide weekly injection; Placebo weekly injection; Insulin
Intervention 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; 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.; 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
Intervention MeSH terms: rGLP-1 protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: New-onset type 1 diabetes mellitus; Albiglutide

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.