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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02284009
First Posted: November 5, 2014
Last Update Posted: November 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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)

Condition Intervention Phase
Diabetes Mellitus, Type 1 Biological: Albiglutide weekly injection Biological: Placebo weekly injection Biological: Insulin Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean change from baseline in stimulated (from Mixed meal tolerance test [MMTT]) plasma C-peptide area under the curve (AUC) at Week 52 [ Time Frame: Week 52 ]

Secondary Outcome Measures:
  • Mean change from baseline in stimulated (from MMTT) plasma C-peptide AUC [ Time Frame: Up to Week 64 ]
  • Maximum stimulated plasma C-peptide [ Time Frame: Up to Week 64 ]
  • Mean change from baseline in plasma glucagon AUC (from MMTT) [ Time Frame: Up to Week 64 ]
  • Percentage of responders [ Time Frame: Up to Week 64 ]
    Responders are defined as subjects with glycosylated haemoglobin A1c (HbA1c) less than 7.0% and insulin dose less than 0.5 units/kg/day

  • Percentage of subjects achieving partial remission status [ Time Frame: Up to Week 64 ]
    A subject achieving partial remission status is defined as a subject with Insulin Adjusted A1c (IDAA1C) less than or equal to 9

  • Change from Baseline in Glycosylated haemoglobin A1c (HbA1c) [ Time Frame: Up to Week 64 ]
  • Change from baseline in mean daily insulin use [ Time Frame: Up to Week 64 ]
  • Glycaemic variability, as measured by 72-hour continuous glucose monitoring (CGM) and 7 point glucose profile [ Time Frame: Up to Week 64 ]
  • Change from Baseline in body weight (kg) [ Time Frame: Up to Week 64 ]
  • Incidence of hypoglycaemia [ Time Frame: Up to Week 64 ]
  • Adverse events and serious adverse events [ Time Frame: Up to Week 64 ]
  • Assessment of clinical laboratory tests [ Time Frame: Up to Week 64 ]
  • Percentage of subjects developing anti-albiglutide antibodies [ Time Frame: Up to Week 64 ]
  • Pharmacokinetic (PK) profile of albiglutide [ Time Frame: Up to Week 16 ]
    Population estimates of PK parameters (apparent clearance [CL/F], apparent volume of distribution [V/F], first-order absorption rate constant [Ka]), associated intersubject variability and residual error)


Enrollment: 67
Actual Study Start Date: October 10, 2014
Study Completion Date: October 18, 2017
Primary Completion Date: October 18, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Albiglutide
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.
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: 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
Experimental: Placebo
Approximately 17 subjects will be assigned to albiglutide matching placebo + background insulin
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02284009


Locations
France
GSK Investigational Site
Amiens Cedex 1, France, 80054
GSK Investigational Site
Bois-Guillaume, France, 76230
GSK Investigational Site
Caen Cedex 9, France, 14033
GSK Investigational Site
Lille Cedex, France, 59037
GSK Investigational Site
Strasbourg cedex, France, 67091
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 80804
GSK Investigational Site
Frankfurt, Hessen, Germany, 60590
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
Italy
GSK Investigational Site
Latina, Lazio, Italy, 04100
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Roma, Italy, 00128
Spain
GSK Investigational Site
Alzira/Valencia, Spain, 46600
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Granada, Spain, 18012
GSK Investigational Site
Hospitalet de Llobregat, Spain, 08907
GSK Investigational Site
Lleida, Spain, 25198
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Málaga, Spain, 29010
GSK Investigational Site
Pama de Mallorca, Spain, 07010
GSK Investigational Site
San Juan (Alicante), Spain, 03550
GSK Investigational Site
Sevilla, Spain, 41014
United Kingdom
GSK Investigational Site
Ayr, United Kingdom, KA6 6DX
GSK Investigational Site
Birmingham, United Kingdom, B9 5SS
GSK Investigational Site
Bristol, United Kingdom, BS2 8HW
GSK Investigational Site
Cardiff, United Kingdom, CF14 4XN
GSK Investigational Site
Darlington, United Kingdom, DL3 6HX
GSK Investigational Site
Dundee, United Kingdom, DD1 9SY
GSK Investigational Site
Durham, United Kingdom, DH1 5TW
GSK Investigational Site
Glasgow, United Kingdom, G31 2ER
GSK Investigational Site
Liverpool, United Kingdom, L7 8XP
GSK Investigational Site
London, United Kingdom, E1 2AT
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
GSK Investigational Site
Sheffield, United Kingdom, S5 7AU
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02284009     History of Changes
Other Study ID Numbers: 110933
First Submitted: September 18, 2014
First Posted: November 5, 2014
Last Update Posted: November 27, 2017
Last Verified: November 2017

Keywords provided by GlaxoSmithKline:
New-onset type 1 diabetes mellitus
Albiglutide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
rGLP-1 protein
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists