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CompletedNCT01648153T2DMUpdated Nov 21, 2016

Investigate the Efficacy and Safety of GSK1070806 in Obese Subjects With T2DM

A Phase 2 interventional study of GSK1070806 and Placebo (saline) in Diabetes Mellitus, sponsored by GlaxoSmithKline. Completed at 14 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2016-11-21.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Basic science

Phase
Phase 2
Study type
Interventional
Enrollment
37
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

GSK1070806 is a humanised IgG1/kappa antibody which is directed against the soluble cytokine interleukin-18 (IL-18). The aims of this placebo controlled study are to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of GSK1070806 in obese subjects with Type 2 diabetes mellitus (T2DM), and to gain a better understanding of the mechanism by which GSK1070806 exerts its therapeutic effects.

Read the detailed description

The study will be a randomised, single-blind (sponsor-unblinded), placebo-controlled, study to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of repeat intravenous infusions (2 doses 4-weeks apart) of GSK1070806 in obese patients with T2DM. The primary objective of the study will be to assess improvements in fasting and postprandial glucose control. This will be a parallel-group study in 30 obese subjects with T2DM who are poorly controlled on metformin monotherapy (HbA1C>7% but \<9.5%), and who have levels of microalbuminuria indicative of progressive kidney disease i.e. 30-300mg/L albumin in urine or ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol (male) and ≤30mg/mmol. There will be three treatment groups comprising two active and one placebo arm with 10 subjects per dose group. The study contains a broad range of biomarker assessments, the purpose of which is to evaluate the mechanistic basis by which GSK1070806 exerts its therapeutic benefit in subjects with T2DM.

Subjects will be randomised into one of the three treatment groups where they will receive two intravenous infusions of GSK1070806 or placebo twenty-eight days apart. A MMT challenge will be conducted on Day 1, Day 29, Day 57 and Day 85 for evaluation of the primary endpoints.

02

Conditions studied

  • Diabetes Mellitus

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Keywords

  • Efficacy
  • Obese
  • T2DM
  • IL-18
  • Monoclonal antibody (mAb)
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,318 are open to participants now.

This study's enrollment of 37 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening.
  2. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
  3. HbA1c levels ≥ 7.0 % and ≤ 9.5%; at Screening.
  4. On a stable dose of monotherapy with metformin for three months prior to screening, and at a total daily dose greater than or equal to 1000 mg for at least 2 months prior to dosing.
  5. Fasting plasma glucose level \< 13.3 mmol/L (240 mg/dL) at screening.
  6. Obese with BMI ≥ 30 kg/m2, and \< 40 kg/m2.
  7. Presence of microalbuminuria: 30-300mg/L albumin in urine or Albumin Creatinine Ratio (ACR) ≥ 3.5 mg/mmol (female) or ≥2.5 mg/mmol (male) and ≤ 30 mg/mmol (female and male)..
  8. The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

  9. A female subject is eligible to participate if she is of:

    • Non-childbearing potential
    • Child-bearing potential and agrees to use an acceptable form of contraception.
  10. Male subjects must agree to use one of the contraception methods listed
  11. ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
  12. Single or Average QTc, QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.

Exclusion criteria

Exclusion Criteria:

  1. Current evidence, or history within the last 7 days, of an influenza-like illness as defined by fever (>38°C) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea in the absence of a known cause, other than influenza.
  2. Use of anti-inflammatory drugs including corticosteroids, chronic maintenance therapy with NSAIDs, anti-Tumor Necrosis Factor (anti-TNF) or anti-Interleukin-1 (anti-IL1) within 60 days prior to dosing.
  3. Current evidence of ongoing or acute infection, history of repeated, chronic or opportunistic infections (e.g. recurrent folliculitis, other cutaneous infections or repeated pneumonia) or history of a serious bacterial infection within 6 months of randomisation.
  4. History of malignancy or significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions.
  5. History chronic granulomatous infections, such as of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
  6. Creatinine clearance less than 60ml/min
  7. Screens positive of Hepatitis B surface antigen, Hepatitis C antibody or Human Immunodeficiency Virus (HIV)
  8. History of a severe allergic reaction, anaphylaxis or immunodeficiency.
  9. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  10. A positive pre-study drug/alcohol screen.
  11. History of regular alcohol consumption within 6 months of the study
  12. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  13. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  14. Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
  15. History of sensitivity to any of the study medications, or components thereof
  16. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  17. Pregnant females as determined by positive serum or urine hCG test at screening.
  18. Lactating females.
  19. Unwillingness or inability to follow the procedures outlined in the protocol.
  20. Subject is mentally or legally incapacitated.
  21. Subject has received a live attenuated vaccine(s) within 30 days of randomisation or will require vaccination with a live attenuated vaccine prior to the end of the study.
05

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
37 participants (actual)

Study arms

  • Active comparator
    GSK1070806 0.25mg/kg

    TwoIV administrations of 0.25mg/kg GSK1070806 4weeks apart

    Biological: GSK1070806

  • Active comparator
    GSK1070806 5mg/kg

    Two IV administrations of 5mg/kg of GSK1070806 4 weeks apart

    Biological: GSK1070806

  • Placebo comparator
    Placebo (Saline)

    Two IV administrations of saline 4 weeks apart

    Other: Placebo (saline)

Interventions

  • BiologicalGSK1070806

    To investigate the efficacy and biomarker changes of GSK1070806 after 0.25mg/kg IV administration

  • OtherPlacebo (saline)

    To compare the efficacy and biomarker changes between placebo and active groups

  • BiologicalGSK1070806

    To investigate the efficacy and biomarker changes of GSK1070806 after 5mg/kg IV administration

06

What researchers measure

Primary outcomes

  1. Change from baseline in fasting plasma glucose and weighted mean glucose AUC (0-4hrs) post-Mixed Meal Test (MMT)

    To evaluate the efficacy of two repeat intravenous dose administrations of GSK1070806 in subjects with T2DM

    Time frame: Up to 85 days after the first does

Secondary outcomes

  1. Safety and tolerability parameters include: adverse events, clinical laboratory tests, electrocardiograms (ECGs), and vital signs

    To evaluate the safety and tolerability of two repeat intravenous dose administrations of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

  2. Change from baseline in % HbA1c, fasting blood insulin, and C-peptide levels; change from baseline in weighted mean insulin, and C-peptide levels [AUC (0-4hrs)] post-MMT and derived measures of insulin sensitive

    To evaluate the effect of two repeat intravenous dose administrations of GSK1070806 on additional markers of efficacy, in obese subjects with T2DM

    Time frame: Up to 85 days after the first dose

  3. AUC(0-τ)

    To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

  4. Serum levels of free IL-18 and drug bound IL 18

    To investigate the effect of repeat intravenous doses of GSK1070806 on free and drug bound IL 18 levels (if measurable) in obese subjects with T2DM.

    Time frame: Up to 210 days after the first dose

  5. Change from baseline in serum and/or plasma levels of biomarkers of inflammation (e.g. hs-CRP, and IL-6) and metabolic disease (e.g. adiponectin, fructosamine, total cholesterol, high-density lipoprotein (HDL)/low-density lipoprotein (LDL), triglycerides

    To explore the pharmacodynamic (PD) effect of repeat intravenous doses of GSK1070806 on biomarkers of inflammation and metabolic disease

    Time frame: Up to 85 days after the first dose

  6. Change from baseline in waist circumference and BMI

    To investigate the effect of repeat intravenous doses of GSK1070806 on body composition in obese subjects with T2DM

    Time frame: Up to 85 days after the first dose

  7. Cmax

    To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

  8. Tmax

    To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

  9. after the second dose λz

    To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

  10. t1/2

    To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM

    Time frame: Up to 210 days after the first dose

07

Study locations

14 sites
  • GSK Investigational Site
    Alicante, 03004, Spain
  • GSK Investigational Site
    Alzira/Valencia, 46600, Spain
  • GSK Investigational Site
    Granada, 18012, Spain
  • GSK Investigational Site
    La Roca del Valles (Barcelona), 08430, Spain
  • GSK Investigational Site
    Lleida, 25198, Spain
  • GSK Investigational Site
    Madrid, 28034, Spain
  • GSK Investigational Site
    Madrid, 28046, Spain
  • GSK Investigational Site
    Malaga, 29010, Spain
  • GSK Investigational Site
    Málaga, 29010, Spain
  • GSK Investigational Site
    Petrer, Alicante, 03610, Spain
  • GSK Investigational Site
    Santander, 39008, Spain
  • GSK Investigational Site
    Birmingham, Warwickshire B15 2TT, United Kingdom
  • GSK Investigational Site
    Cambridge, CB2 2GG, United Kingdom
  • GSK Investigational Site
    Dundee, DD1 9SY, United Kingdom
08

References and documents

Publications

  • McKie EA, Reid JL, Mistry PC, DeWall SL, Abberley L, Ambery PD, Gil-Extremera B. A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus. PLoS One. 2016 Mar 1;11(3):e0150018. doi: 10.1371/journal.pone.0150018. eCollection 2016. PubMed 26930607 ↗

Individual participant data

Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 21, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01648153
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jul 24, 2012
Start date
Aug 2012
Primary completion
Sep 2013
Completion
Jan 2014
Last update
Nov 21, 2016

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2016. You cannot join it, but the record below documents what was studied.

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