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safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.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
Location
GSK Investigational Site
Boca Raton, Florida, United States, 33486
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02111
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Location
GSK Investigational Site
Bury St. Edmunds, Suffolk, United Kingdom, IP33 2QZ
Status
Study Complete
Location
GSK Investigational Site
Camperdown, New South Wales, Australia, 2050
Status
Study Complete
Location
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Jackson, Tennessee, United States, 38305
Status
Study Complete
Location
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Status
Study Complete
Location
GSK Investigational Site
Malvern East, Victoria, Australia, 3145
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10021
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Reggio Emilia, Emilia-Romagna, Italy, 42100
Status
Study Complete
Location
GSK Investigational Site
Rochester, Minnesota, United States, 55905
Status
Study Complete
Location
GSK Investigational Site
Seattle, Washington, United States, 98101
Status
Study Complete
Location
GSK Investigational Site
Sheffield, Yorkshire, United Kingdom, S10 2JF
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Vancouver, Washington, United States, 98664
Status
Study Complete
Location
GSK Investigational Site
Victoria Park, Western Australia, Australia, 6100
Status
Study Complete
Location
GSK Investigational Site
Westcliff-on-Sea, Essex, United Kingdom, SS0 0RY
Status
Study Complete
Location
GSK Investigational Site
Wirral, Merseyside, United Kingdom, CH49 9PE
Status
Study Complete
Location
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Status
Study Complete
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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