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Diabetes MellitusPhase 2T2DMNCT01648153

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

A Phase 2 study testing GSK1070806 in people with Diabetes Mellitus, run by GlaxoSmithKline at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diabetes Mellitus
What is being tested?
GSK1070806
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
37 participants
Where
13 sitesin 2 countries
Study dates
Aug 2012to Jan 2014
Phase
Phase 2
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Pregnant females as determined by positive serum or urine hCG test at screening.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • 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.

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Spain10 sites
  • GSK Investigational Site

    Alicante, 03004

  • GSK Investigational Site

    Alzira/Valencia, 46600

  • GSK Investigational Site

    Granada, 18012

  • GSK Investigational Site

    La Roca Del Valles (Barcelona), 08430

  • GSK Investigational Site

    Lleida, 25198

  • GSK Investigational Site

    Madrid, 28034

  • GSK Investigational Site

    Madrid, 28046

  • GSK Investigational Site

    Málaga, 29010

  • GSK Investigational Site

    Petrer, Alicante, 03610

  • GSK Investigational Site

    Santander, 39008

Other trials in Spain

United Kingdom3 sites
  • GSK Investigational Site

    Birmingham, Warwickshire, B15 2TT

  • GSK Investigational Site

    Cambridge, CB2 2GG

  • GSK Investigational Site

    Dundee, DD1 9SY

Other trials in United Kingdom

About this study

Official title: A Single Blind (Sponsor-unblinded), Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of GSK1070806 in the Treatment of Obese Subjects With T2DM.

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.

Being tested
GSK1070806, Placebo (saline)
Keywords
Efficacy, Obese, T2DM, IL-18, Monoclonal antibody (mAb)
Medical subject headings
Diabetes Mellitus, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1070806Biological

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

  • Placebo (saline)Other

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

  • GSK1070806Biological

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

Study groups in NCT01648153
Study groupRoleWhat they receive
GSK1070806 0.25mg/kgActive comparatorTwoIV administrations of 0.25mg/kg GSK1070806 4weeks apart
Receives: Biological: GSK1070806
GSK1070806 5mg/kgActive comparatorTwo IV administrations of 5mg/kg of GSK1070806 4 weeks apart
Receives: Biological: GSK1070806
Placebo (Saline)Placebo comparatorTwo IV administrations of saline 4 weeks apart
Receives: Other: Placebo (saline)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 85 days after the first does

Secondary outcomes (10)
  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

    Measured: 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

    Measured: 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

    Measured: 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.

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: Up to 210 days after the first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionSep 2013
  4. Study completionJan 2014

Resources

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
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01648153
Sponsor's protocol ID
116378
Acronym
T2DM
Status last verified
Nov 2016
First submitted
12 Jul 2012
Last updated
21 Nov 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK1070806 in people with Diabetes Mellitus, run by GlaxoSmithKline at 13 sites in 2 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 14 inclusion and 21 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 21 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, United Kingdom. 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change from baseline in fasting plasma glucose and weighted mean glucose AUC (0-4hrs) post-Mixed Meal Test (MMT) (time frame: Up to 85 days after the first does). 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 NCT01648153, 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 21 Nov 2016.

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