| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Recently diagnosed type 1 diabetes mellitus |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012594 |
| E.1.2 | Term | Diabetes |
| E.1.2 | System Organ Class | 100000019275 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • Determine the effect of albiglutide therapy versus placebo on endogenous insulin secretion over 52 weeks when added to standard of care in subjects with new onset type 1 diabetes mellitus (NOT1DM) |
|
| E.2.2 | Secondary objectives of the trial |
•To assess the effect of albiglutide versus placebo on plasma glucagon concentration during a MMTT
•Determine the percentage of subjects meeting the definition of a responder (defined as having HbA1c ≤ 7.0% and mean daily insulin use < 0.5 units/kg/day) and the percentage of subjects achieving partial remission status (i.e., defined as subjects with Insulin Dose Adjusted A1c (IDAA1C LTET 9.0)
•To assess glycaemic control in both treatment groups as measured by HbA1c
•Determine differences in total daily insulin dose between treatment groups
•Determine any differences in significant hypoglycaemia (i.e., events with plasma glucose < 3.9 mmol/L and/or requiring third party intervention) between treatment groups
•Compare glycaemic variability between treatment groups, as measured by 72-hour continuous glucose monitoring (CGM) and 7 point glucose profile
•Determine the effect of albiglutide on body weight
Please refer to the protocol P24 for further deatils. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 β-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 [UK only: this method of contraception is acceptable only if used with a vaginal spermicide].
7. Able and willing to provide written informed consent and to comply with all study procedures. |
|
| E.4 | Principal 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 within the 3 months before randomisation, or receipt of albiglutide in previous studies |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in stimulated (from MMTT) 2 hour plasma C-peptide area under the curve (AUC) at Week 52 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Mean change from baseline in stimulated 2 hour plasma C-peptide AUC (from MMTT) at Week 16, 28 and Week 64
• Maximum stimulated plasma C-peptide: the highest value at any time point during the MMTT after the subject has ingested the mixed meal at Baseline, Week 16, Week 28, Week 52 and Week 64
• Mean change from baseline in glucagon AUC (from MMTT) at Week 16, 28, 52 and Week 64
• Percent of responders (as defined as subjects with HbA1c < 7.0% and insulin dose < 0.5 units/kg/day) at Weeks 4, 8, 16, 28, 40, 52 and 64
• Percent of subjects achieving insulin dose-adjusted haemoglobin A1c (IDAA1C) less than 9 at Weeks 4, 8, 16, 28, 40, 52 and 64
• Change from Baseline in HbA1c at Week 52 and HbA1c over time (i.e., at Weeks 4, 8, 16, 28, 40, 52 and 64
• Change from baseline in mean daily insulin use over the 3 days preceding the visit at Weeks 4, 8, 16, 28, 40, 52 and 64. The mean daily insulin use value will be calculated in units/kg/day, as the mean of the values of amount of insulin used per day on each of the 3 consecutive days
• Number of events of hypoglycaemia with confirmed self plasma glucose monitoring < 3.9 mmol/L and/or requiring 3rd party intervention (i.e., severe, documented symptomatic and asymptomatic events see Section 6.4.2) occurring > Week 24 and greater than Week 52.
• Number and magnitude of hypoglycaemic (<3.9 mmol/L) and hyperglycaemic excursions (> 10.0 mmol/L) from the 7 point glucose profile at Baseline, Week 28 and Week 52
• Time spent with a plasma glucose <3.9 mmol/L, between 3.9 and 10.0 mmol/L, and >10.0 mmol/L, respectively as performed by 72-hour CGM at Baseline, Week 28 and Week 52
• Change from Baseline in body weight (kg) at Week 52 and Weight over time (i.e., at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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