Albiglutide versus Placebo in New-Onset Type 1 Diabetes Mellitus

Phase 1

• Conditions: Type 1 diabetes mellitus; MedDRA version: 17.0Level: LLTClassification code 10012594Term: DiabetesSystem Organ Class: 100000004861; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2014-001825-33-IT
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-08-20
• Last Update Posted: 5 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. 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.
2. Currently requires insulin for T1DM treatment, or has required insulin therapy for T1DM (for greater than 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.
3. 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 =7 days.
4. Evidence of residual functioning pancreatic ß-cells as measured by a peak stimulated C-peptide level > 0.20 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.
5. Body mass index = 32.0 kg/m2.
6. 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
7. Able and willing to provide written informed consent and to comply with all study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Severe gastroparesis i.e., requiring therapy within 6 months prior to Screening
2. 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).
3. 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)
4. Personal history or family history of thyroid medullary carcinoma or multiple endocrine neoplasia type 2 (MEN2)
5. 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)
6. Fasting triglyceride level >750 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
7. Estimated Glomerular Filtration Rate (eGFR LTET 30 mL/min/1.73 m2 (calculated using the Modification of Diet in Renal Disease (MDRD) formula
8. Haemoglobinopathy that may affect proper interpretation of HbA1c
9. 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%)
10. 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)]
11. 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
12. Female subject is pregnant (confirmed by laboratory testing) or lactating
13. Known allergy to any GLP 1 analogue, insulin, or excipients of albiglutide
14. Treatment with any oral anti-diabetic medication within the prior 30 days or 5 half-lives of that medication, whichever is longer.
15. 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
16. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified