Last updated: 07/17/2024 17:11:29
Efficacy and Safety Study of Sirukumab in Patients with Giant Cell Arteritis
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
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 Arteritis
Trial description: 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safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: Week 52
Secondary outcomes:
Part A & B: Cumulative prednisone doses in subjects treated with sirukumab plus prednisone
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Proportion of subjects in sustained remission
Timeframe: At Week 52 (Part A) and from Week 52 to Week 78 (Part B)
Part A & B: Measure of remission rates over time
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Time to first GCA flare
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Number of disease flares per subject over time
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Safety: Incidence of adverse events
Timeframe: 52 Weeks (Part A) and 120 Weeks (Part B)
Part A & B: Safety: Incidence of corticosteroid-related adverse events
Timeframe: 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
Timeframe: 52 Weeks (Part A) and 120 Weeks (Part B)
Part A & B: Composite of clinical laboratory tests assessment as a measure of safety: clinical chemistry and hematology
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A: Assessment of Patient Global Impression of Change (PGIC)
Timeframe: Up to Week 52
Part A & B: Pain assessment
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Health Assessment Questionnaire-Disability Index (HAQ-DI)
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Assessment of steroid impact
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Assessment of quality of life using the 36-item Short Form Version 2 Acute (SF-36v2 Acute)
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A & B: Assessment of health status using the EuroQoL-5D (EQ-5D)
Timeframe: 52 Weeks (Part A) and 104 Weeks (Part B)
Part A: Pharmacodynamics: Change from baseline in erythrocyte sedimentation rate (ESR) over time
Timeframe: Up to Week 52
Part A: Pharmacodynamics: Change from baseline in serum C-reactive protein (CRP) over time
Timeframe: Up to Week 52
Part A: Pharmacokinetics: Serum concentrations of sirukumab
Timeframe: Up to Week 44
Part A & B: Immunogenicity: Serum anti-sirukumab antibodies
Timeframe: 52 Weeks (Part A) and 120 Weeks (Part B)
Interventions:
Enrollment:
161
Primary completion date:
2018-21-03
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
W. Schmidt, B. Dasgupta, R. Luqmani, S. Unizony, D. Blockmans, Z. Lai, R. Kurrasch, I. Lazic, K. Brown, R. Rao.A Multicenter, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis .Rheumatol Ther.2020;
DOI: 10.1007/s40744-020-00227-2
Medical condition
Giant Cell Arteritis
Product
sirukumab
Collaborators
Not applicable
Study date(s)
October 2015 to March 2018
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
50+ years
Accepts healthy volunteers
No
- Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria:
- Age >=50 years.
- Are pregnant or breastfeeding.
- Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments.
Inclusion and exclusion criteria
Inclusion criteria:
- Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria: Age >=50 years. History of ESR >=50 millimeter/hour (mm/hour) or CRP >=2.45 milligram/deciliter(mg/dL). Presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of polymyalgia rheumatic (PMR). Presence of at least one of the following: Temporal artery biopsy revealing features of GCA; Evidence of large-vessel vasculitis by angiography or cross-sectional imaging.
- Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined by an ESR >=30 mm/hr or CRP >=1 mg/dL AND the presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of PMR; Other features judged by the clinician investigator to be consistent with GCA or PMR flares.
- At screening, receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA.
- Clinically stable GCA disease at baseline such that the subject is able to safely participate in the blinded prednisone taper regimen in the opinion of the investigator.
- Practicing acceptable methods of birth control if a female of child-bearing potential.
- No evidence of active or latent infection with Mycobacterium tuberculosis (TB).
Exclusion criteria:
- Are pregnant or breastfeeding.
- Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments.
- Organ transplantation recipients (except corneas within 3 months prior to baseline visit).
- Had prior treatment with any of the following: Systemic immunosuppressives) within 4 weeks of baseline; Biologic agents targeted at reducing tumor necrosis factor-alpha (TNF-alpha) within 2-8 weeks of baseline, depending on the agent; Any prior use of tocilizumab or other anti-IL-6 agents; B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels; Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline; Abatacept within 8 weeks of baseline; Tofacitinib within 4 weeks of baseline; Methotrexate use within 2 weeks of baseline. Methylprednisolone > 100 mg/day intravenous (IV) (or equivalent) within 8 weeks of baseline.
- History of severe allergic reactions to monoclonal antibodies, human proteins, or excipients.
- Evidence of serious concomitant disease, which in the opinion of the investigator makes them unsuitable for participation in the study.
- Major ischemic event, unrelated to GCA, within 12 weeks of screening.
- Marked baseline prolongation of corrected QT (QTc) interval >= 450 milliseconds (msec) (QTc by Bazett's formula [QTcB ]or QTc by Fridericia's formula [QTcF] ), history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block.
- Current liver disease that could interfere with the trial
- History of or current active diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation.
- History of known demyelinating diseases such as multiple sclerosis or optic neuritis.
- Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows: Currently on any suppressive therapy for a chronic infection, history or suspicion of chronic infection, hospitalization for treatment of infection within 60 days of the baseline visit, or use of parenteral (IV) or intra-muscular [IM]) antimicrobials within 60 days of baseline or oral antimicrobials within 30 days of baseline
- Primary or secondary immunodeficiency or any other autoimmune disease.
- Human immunodeficiency virus (HIV) infection, hepatitis C or hepatitis B infection
- Live virus or bacterial vaccination within 3 months before the first administration of study drug
Trial location(s)
Location
GSK Investigational Site
Aurora, Colorado, United States, 80210
Status
Study Complete
Showing 1 - 6 of 63 Results
Study documents
Clinical study report
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2018-21-03
Actual study completion date
2018-21-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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