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

NCT01648153 | Completed Phase 2

• 1 other identifier: 116378
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 13

Brief 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.

Conditions

Diabetes Mellitus

Keywords

Efficacy; Obese; T2DM; IL-18; Monoclonal antibody (mAb)

Outcome Measures

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

  Up to 85 days after the first does

Secondary Outcomes (10)

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

  Up to 210 days after the first dose

• 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

  Up to 85 days after the first dose

• AUC(0-τ)

  Up to 210 days after the first dose

• Serum levels of free IL-18 and drug bound IL 18

  Up to 210 days after the first dose

• 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

  Up to 85 days after the first dose

Study Arms (3)

GSK1070806 0.25mg/kg

ACTIVE COMPARATOR

TwoIV administrations of 0.25mg/kg GSK1070806 4weeks apart

Biological: GSK1070806

GSK1070806 5mg/kg

ACTIVE COMPARATOR

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

Biological: GSK1070806

Placebo (Saline)

PLACEBO COMPARATOR

Two IV administrations of saline 4 weeks apart

Other: Placebo (saline)

Interventions

GSK1070806 BIOLOGICAL

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

GSK1070806 0.25mg/kg

Placebo (saline) OTHER

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

Placebo (Saline)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• HbA1c levels ≥ 7.0 % and ≤ 9.5%; at Screening.
• 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.
• Fasting plasma glucose level \< 13.3 mmol/L (240 mg/dL) at screening.
• Obese with BMI ≥ 30 kg/m2, and \< 40 kg/m2.
• 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)..
• The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• 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.
• Male subjects must agree to use one of the contraception methods listed
• ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Single or Average QTc, QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.

You may not qualify if:

• 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.
• 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.
• 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.
• History of malignancy or significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions.
• History chronic granulomatous infections, such as of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
• Creatinine clearance less than 60ml/min
• Screens positive of Hepatitis B surface antigen, Hepatitis C antibody or Human Immunodeficiency Virus (HIV)
• History of a severe allergic reaction, anaphylaxis or immunodeficiency.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• History of regular alcohol consumption within 6 months of the study
• 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).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• 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.
• History of sensitivity to any of the study medications, or components thereof

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Alicante, 03004, Spain

Location

GSK Investigational Site

Alzira/Valencia, 46600, Spain

Location

GSK Investigational Site

Granada, 18012, Spain

Location

GSK Investigational Site

La Roca Del Valles (Barcelona), 08430, Spain

Location

GSK Investigational Site

Lleida, 25198, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Petrer, Alicante, 03610, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Birmingham, Warwickshire, B15 2TT, United Kingdom

Location

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26930607 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Diabetes Mellitus; Obesity

Interventions

GSK1070806; Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 24, 2012
• Study Start: August 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: January 1, 2014
• Last Updated: November 21, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); ES (10)