Clinical Trial: Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Patients With Giant Cell Ar
Brief Summary:
Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule that may have therapeutic benefit in the treatment of giant cell arteritis (GCA) by interruption of multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active GCA. The study will be conducted in 2 distinct parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 104-week extension phase with the option to receive open-label sirukumab based on disease status and a 16-week follow-up phase if applicable.
Approximately 204 subjects with a diagnosis of GCA and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study will be eligible to enter Part B, the 104-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects with active GCA at the end of Part A or those with new onset of GCA flare during the first 52 weeks of Part B will be eligible to receive open-label sirukumab. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely
Detailed Summary:
Sponsor: GlaxoSmithKline
Current Primary Outcome: Proportion of subjects in sustained remission at Week 52 for sirukumab (100 mg every 2 weeks [q2w] for 12 months) as compared to placebo, each administered in addition to a 6-month prednisone treatment regimen [ Time Frame: Week 52 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Part A & B: Cumulative prednisone doses in subjects treated with sirukumab plus prednisone [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Median and cumulative prednisone dose over time
- Part A & B: Proportion of subjects in sustained remission [ Time Frame: At Week 52 (Part A) and from Week 52 to Week 78 (Part B) ]
- Part A & B: Measure of remission rates over time [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Proportion of subjects in remission at all time points of assessment
- Part A & B: Time to first GCA flare [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Time to first GCA flare after clinical remission
- Part A & B: Number of disease flares per subject over time [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]
- Part A & B: Safety: Incidence of adverse events [ Time Frame: 52 Weeks (Part A) and 120 Weeks (Part B) ]
- Part A & B: Safety: Incidence of corticosteroid-related adverse events [ Time Frame: 52 Weeks (Part A) and 120 Weeks (Part B) ]
- Part A & B: Composite of vital signs assessment as a measure of safety: blood pressure, pulse rate and temperature [ Time Frame: 52 Weeks (Part A) and 120 Weeks (Part B) ]Vital signs assessment will include systolic and diastolic blood pressure, pulse rate and body temperature
- Part A & B: Composite of clinical laboratory tests assessment as a measure of safety: clinical chemistry and hematology [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Clinical laboratory tests will include clinical chemistry and hematology
- Part A: Assessment of Patient Global Impression of Change (PGIC) [ Time Frame: Up to Week 52 ]Estimate of the magnitude of patient response to treatment at different time points by patient report
- Part A & B: Pain assessment [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Average pain assessed by patient report of rating on score of 0 to 100
- Part A & B: Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Patient reported outcome of difficulties in 8 functional areas
- Part A & B: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Patient report of elements of fatigue
- Part A & B: Assessment of steroid impact [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Patient assessment of the side effects and impact of steroids on GCA symptoms over time
- Part A & B: Assessment of quality of life using the 36-item Short Form Version 2 Acute (SF-36v2 Acute) [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Patient report of quality of life
- Part A & B: Assessment of health status using the EuroQoL-5D (EQ-5D) [ Time Frame: 52 Weeks (Part A) and 104 Weeks (Part B) ]Patient report of health status
- Part A: Pharmacodynamics: Change from baseline in erythrocyte sedimentation rate (ESR) over time [ Time Frame: Up to Week 52 ]
- Part A: Pharmacodynamics: Change from baseline in serum C-reactive protein (CRP) over time [ Time Frame: Up to Week 52 ]
- Part A: Pharmacokinetics: Serum concentrations of sirukumab [ Time Frame: Up to Week 44 ]Blood samples will be collected at Baseline (Week 0), Week 2, 4, 8, 12, 16, 20, 24, 28,and at Week 44 for determination for serum concentrations of sirukumab
- Part A & B: Immunogenicity: Serum anti-sirukumab antibodies [ Time Frame: 52 Weeks (Part A) and 120 Weeks (Part B) ]Blood samples will be collected at Baseline (Week 0), Week 24, 44, 52 of Part A and Baseline (Week 52 of Part A), Week 12, 52, 104 of Part B and at Follow up (Week 120) for determination of serum anti-sirukumab antibodies
Original Secondary Outcome: Same as current
Information By: GlaxoSmithKline
Dates:
Date Received: July 6, 2015
Date Started: October 16, 2015
Date Completion: November 27, 2020
Last Updated: April 17, 2017
Last Verified: April 2017