Diabetes Mellitus, Type 1Phase 2NCT02284009
Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
A Phase 2 study testing Albiglutide weekly injection and Insulin in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 32 sites in 5 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 30 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Albiglutide weekly injection and Insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 32 sitesin 5 countries
- Study dates
- 10 Oct 2014to 18 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
32 sites in 5 countries.
32 sites in 5 countries
Spain11 sites
GSK Investigational Site
Alzira/Valencia, 46600
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
Granada, 18012
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Lleida, 25198
GSK Investigational Site
Madrid, 28006
GSK Investigational Site
Málaga, 29010
GSK Investigational Site
Pama de Mallorca, 07010
GSK Investigational Site
San Juan (Alicante), 03550
GSK Investigational Site
Seville, 41014
United Kingdom11 sites
GSK Investigational Site
Birmingham, B9 5SS
GSK Investigational Site
Bristol, BS2 8HW
GSK Investigational Site
Cardiff, CF14 4XN
GSK Investigational Site
Darlington, DL3 6HX
GSK Investigational Site
Dundee, DD1 9SY
GSK Investigational Site
Durham, DH1 5TW
GSK Investigational Site
Glasgow, G31 2ER
GSK Investigational Site
Liverpool, L7 8XP
GSK Investigational Site
London, E1 2AT
GSK Investigational Site
Newcastle upon Tyne, NE1 4LP
GSK Investigational Site
Sheffield, S5 7AU
Germany4 sites
GSK Investigational Site
Dresden, Saxony, 01307
GSK Investigational Site
Düsseldorf, North Rhine-Westphalia, 40225
GSK Investigational Site
Frankfurt am Main, Hesse, 60590
GSK Investigational Site
Munich, Bavaria, 80804
France3 sites
GSK Investigational Site
Bois-Guillaume, 76230
GSK Investigational Site
Caen, 14033
GSK Investigational Site
Lille, 59037
Italy3 sites
GSK Investigational Site
Latina, Lazio, 04100
GSK Investigational Site
Milan, Lombardy, 20132
GSK Investigational Site
Roma, 00128
About this study
Official title: Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
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
- Being tested
- Albiglutide weekly injection, Placebo weekly injection, Insulin
- Keywords
- New-onset type 1 diabetes mellitus, Albiglutide
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Albiglutide weekly injectionBiological
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 weekly injectionBiological
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.
InsulinBiological
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Albiglutide weekly injection; Biological: Insulin |
| Placebo | Experimental | Approximately 17 subjects will be assigned to albiglutide matching placebo + background insulin Receives: Biological: Placebo weekly injection; Biological: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Baseline and Weeks 16, 28 and 64
Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 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.
Measured: 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
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.
Measured: Baseline and Weeks 16, 28, 52 and 64
Percentage of Responders at Baseline, 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.
Measured: 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
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.
Measured: Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Change From Baseline in Percent HbA1c at 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.
Measured: Baseline and Week 52
Percent HbA1c Over Time (at 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.
Measured: 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
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.
Measured: Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 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.
Measured: Week 24 to 52
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
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.
Measured: Baseline and Weeks 28 and 52
Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
A hypoglycemic excursion was defined as an occurrence where the plasma glucose level <=3.9 mmol/L (<=70 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hypoglycemic excursions were included. Number of Hypoglycemic Excursions for each participant from 7-Point Glucose Profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime) were reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Measured: Baseline and Weeks 28 and 52
Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
A hypoglycemic excursion was defined as an occurrence where the plasma glucose level <=3.9 mmol/L (<= 70 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hypoglycemic excursions were included. Greatest hypoglycemic excursion was calculated as 3.9 mmol/L minus the lowest recorded glucose level during the 7-point glucose profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime). If a participant had data recorded at that visit, but did not have a value <= 3.9 mmol/L, their greatest hypoglycemic excursion were 0 mmol/L for that visit. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Measured: Baseline and Weeks 28 and 52
Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
A hyperglycemic excursion is defined as an occurrence where the plasma glucose level > 10.0 mmol/L (> 180 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hyperglycemic excursions were included. Number of Hyperglycemic Excursions for each participant from 7-Point Glucose Profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime) were reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Measured: Baseline and Weeks 28 and 52
Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
A hyperglycemic excursion is defined as an occurrence where the plasma glucose level > 10.0 mmol/L (> 180 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hyperglycemic excursions were included. Greatest hyperglycemic excursion was calculated as the largest recorded glucose level during the 7-point glucose profile (before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, at bedtime) minus 10.0 mmol/L. If a participant had data recorded at that visit, but does not have a value > 10.0 mmol/L, their greatest hyperglycemic excursion would be 0 mmol/L for that visit. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Measured: Baseline and weeks 28 and 52
Change From Baseline in Body Weight (Kilograms) at Week 52
Change from Baseline in body weight of participants 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 the Baseline value from the Week 52 value.
Measured: Baseline and Week 52
Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
Body weight was measured in kilograms for participants at indicated time points.
Measured: Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64
Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F]
PK of Albiglutide was evaluated in participants using CL/F using PK samples collected on Weeks 4, 6, 8, 16. CL/F was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean body weights of 67 kilograms, and electronic glomerular filtration rate (eGFR) of 123 milliliters per minute.
Measured: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F]
PK of Albiglutide was evaluated in participants using V/F using PK samples collected on Weeks 4, 6, 8, 16. V/F was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean body weights of 67 kilograms, and eGFR of 123 milliliters per minute.
Measured: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka]
PK of Albiglutide was evaluated in participants using Ka using PK samples collected on Weeks 4, 6, 8, 16. Ka was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 67 kilograms, and eGFR of 123 milliliters per minute.
Measured: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study start10 Oct 2014
- Primary completion18 Oct 2017
- Study completion18 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02284009
- Sponsor's protocol ID
- 110933
- Status last verified
- Jun 2020
- First submitted
- 18 Sep 2014
- Last updated
- 29 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
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.
PubMed 32219329
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02284009
- Acronym / sponsor ID
- 110933
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- New-onset type 1 diabetes mellitus, Albiglutide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Oct 2014 (actual)
- Primary completion
- 18 Oct 2017 (actual)
- Study completion
- 18 Oct 2017 (actual)
- First posted
- 5 Nov 2014 (estimated)
- Results
- Posted 25 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albiglutide | Experimental | Biological: Albiglutide weekly injection, Biological: InsulinApproximately 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. |
| Placebo | Experimental | Biological: Placebo weekly injection, Biological: InsulinApproximately 17 subjects will be assigned to albiglutide matching placebo + background insulin |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Albiglutide weekly injectionAlbiglutide 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 | Albiglutide |
| Placebo weekly injectionPlacebo 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 | Placebo |
| InsulinCommercially available basal/bolus insulin regimen, self administered by the subject, in accordance to the prescription of the physician and as per the package insert | Biological | Albiglutide, Placebo |
Primary outcome
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.
19 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
Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64
Time frame: 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
Time frame: Baseline and Weeks 16, 28, 52 and 64
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
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
Change From Baseline in Percent HbA1c at Week 52
Time frame: Baseline and Week 52
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
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
Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52
Time frame: Week 24 to 52
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
Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Time frame: Baseline and Weeks 28 and 52
Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Time frame: Baseline and Weeks 28 and 52
Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Time frame: Baseline and Weeks 28 and 52
Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Time frame: Baseline and weeks 28 and 52
Change From Baseline in Body Weight (Kilograms) at Week 52
Time frame: Baseline and Week 52
Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
Time frame: Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64
Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F]
Time frame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F]
Time frame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka]
Time frame: 48 hours after the most recent dose at Week 4, 6, 8 and 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32219329Pozzilli 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.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
32 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Albiglutide weekly injection and Insulin in people with Diabetes Mellitus, Type 1, run by GlaxoSmithKline at 32 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Spain, United Kingdom, Germany, France, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02284009, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2020.