Current partner codePEPTIDESDE
NCT02284009·Phase 2·INTERVENTIONAL

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

Status

Completed

Phase

Phase 2

Enrollment

67

Locations

32

Results

Posted

Publications

1

Study summary

What the protocol is testing.

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)

Interventions

Treatment arms and agents.

BIOLOGICAL

Albiglutide weekly injection

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

BIOLOGICAL

Placebo weekly injection

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.

BIOLOGICAL

Insulin

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

Timeline

From registration to results.

  1. First posted

    Nov 5, 2014

  2. Study start

    Oct 10, 2014

  3. Primary completion

    Oct 18, 2017

  4. Study completion

    Oct 18, 2017

  5. Results posted

    Mar 25, 2019

  6. Registry updated

    Jun 29, 2020

Outcomes

What the study measures.

Primary outcomes

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

Time frame · Baseline and 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.

Secondary outcomes

Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64

Time frame · Baseline and Weeks 16, 28 and 64

Participants had a balanced diet consistent with dietitian's advice and made no major changes in exercise regimens. On the evening before the MMTT, participants had a full meal and then fasted from 9 pm until the MMTT was completed. Water, black coffee or tea without sugar or artificial sweeteners was allowed. Plasma glucose was measured prior to the test using a finger-stick test and MMTT was performed only if it was in range \> 3.9 mmol/L (70 mg/dL) and \<= 11.1 mmol/L (200 mg/dL). Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64

Time frame · Baseline and Weeks 16, 28, 52 and 64

Maximum stimulated plasma C-peptide was the highest value at any time point during the 2 hour MMTT after the participant has ingested the mixed meal at Baseline, Week 16, Week 28, Week 52 and Week 64. Blood samples were taken to assess levels of C-peptide at: 10 minutes before Time 0 (-10 minutes), Immediately before the participant starts drinking the nutritional drink (Time 0) and 15, 30, 60, 90, and 120 minutes after Time 0.

Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64

Time frame · Baseline and Weeks 16, 28, 52 and 64

Blood samples were taken to assess levels of glucagon at: 10 minutes before Time 0 (-10 minutes), immediately before the participant started drinking the nutritional drink (Time 0) and 15, 30, 60, 90, and 120 minutes after Time 0. Mean change from Baseline in time normalized plasma glucagon AUC (from MMTT) at Week 16, 28, 52 and 64 was reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64

Time frame · Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64

Responders were defined as participants achieving glycosylated hemoglobin A1c (HbA1c) \<= 7.0 percent and mean daily insulin use \< 0.5 units per kilograms (kg) per day. Percentages are based on the number of participants with available HbA1c and insulin use data in each treatment group at that visit.

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

Time frame · Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64

Participant achieving partial remission status was defined as a participant with IDAA1C \<=9.0 . Percentages were based on the number of participants with available IDAA1c data in each treatment group at that visit.

Change From Baseline in Percent HbA1c at Week 52

Time frame · Baseline and Week 52

Change from Baseline in percent HbA1c was reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the Week 52 value.

Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64)

Time frame · Weeks 4, 8, 16, 28, 40, 52 and 64

Blood samples were collected from participants for analysis of HbA1c at indicated time points and percentage of HbA1c has been calculated for Weeks 4, 8, 16, 28, 40, 52 and 64.

Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64

Time frame · Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64

The mean daily insulin use value was calculated, in units/kg/day as the sum of average prandial insulin doses and average of basal insulin doses for each participant recorded daily for the 3 days prior to the specified visits, divided by the participant's body weight in kg. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52

Time frame · Week 24 to 52

Significant hypoglycemia was defined as an event with plasma glucose level \<= 3.9 mmol/L (\<= 70 mg/dL) and/or requiring third party intervention. This corresponds to American Diabetes Association (ADA) category definitions of severe, documented symptomatic, and asymptomatic hypoglycemia. The time period was defined as: \> Week 24 to \<= Week 52 = Day 169 to Day 364. Number of Events were defined as the total number of significant hypoglycemic events at each level of summarization. Number of events of hypoglycemia with confirmed self plasma glucose monitoring \<=3.9 mmol/L and/or requiring third party intervention (i.e., severe, documented symptomatic and asymptomatic hypoglycemic events) occurring \>Week 24 and \<=Week 52 are presented.

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

Time frame · Baseline and Weeks 28 and 52

Three days before the visit, the participants made an additional visit to the study site to have the CGM fitted/inserted. It was worn for 3 consecutive days and was removed at the scheduled study visit. Whilst wearing the CGM, participants continued to monitor their plasma glucose at least 4 times a day and on one of the days, conducted 7-point glucose profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime). Time spent with a plasma glucose \<=3.9 millimoles per liter (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 was reported.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
30 Years
Sex
ALL
Healthy volunteers
No

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.

Study locations

32 registered sites.

France · Germany · Italy · Spain · United Kingdom. Showing up to 24 locations stored in the fast local snapshot.

GSK Investigational Site

Bois-Guillaume, France

GSK Investigational Site

Caen, France

GSK Investigational Site

Lille, France

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Latina, Lazio, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Roma, Italy

GSK Investigational Site

Alzira/Valencia, Spain

GSK Investigational Site

Badalona, Spain

GSK Investigational Site

Barcelona, Spain

GSK Investigational Site

Granada, Spain

GSK Investigational Site

L'Hospitalet de Llobregat, Spain

GSK Investigational Site

Lleida, Spain

GSK Investigational Site

Madrid, Spain

GSK Investigational Site

Málaga, Spain

GSK Investigational Site

Pama de Mallorca, Spain

GSK Investigational Site

San Juan (Alicante), Spain

GSK Investigational Site

Seville, Spain

GSK Investigational Site

Birmingham, United Kingdom

GSK Investigational Site

Bristol, United Kingdom

GSK Investigational Site

Cardiff, United Kingdom

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More studies on Albiglutide.

Related PeptideStat pages

Put the record in context.

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