Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Giant Cell Arteritis
Intervention: Sirukumab (Drug); Placebo to match sirukumab (Drug); Prednisone (Drug); Placebo to match prednisone (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
Overall contact: US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
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 from the study or whose open-label sirukumab treatment in Part B completes after
Week 88.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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
Secondary outcome: Part A & B: Cumulative prednisone doses in subjects treated with sirukumab plus prednisonePart A & B: Proportion of subjects in sustained remission Part A & B: Measure of remission rates over time Part A & B: Time to first GCA flare Part A & B: Number of disease flares per subject over time Part A & B: Safety: Incidence of adverse events Part A & B: Safety: Incidence of corticosteroid-related adverse events Part A & B: Composite of vital signs assessment as a measure of safety: blood pressure, pulse rate and temperature Part A & B: Composite of clinical laboratory tests assessment as a measure of safety: clinical chemistry and hematology Part A: Assessment of Patient Global Impression of Change (PGIC) Part A & B: Pain assessment Part A & B: Health Assessment Questionnaire-Disability Index (HAQ-DI) Part A & B: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Part A & B: Assessment of steroid impact Part A & B: Assessment of quality of life using the 36-item Short Form Version 2 Acute (SF-36v2 Acute) Part A & B: Assessment of health status using the EuroQoL-5D (EQ-5D) Part A: Pharmacodynamics: Change from baseline in erythrocyte sedimentation rate (ESR) over time Part A: Pharmacodynamics: Change from baseline in serum C-reactive protein (CRP) over time Part A: Pharmacokinetics: Serum concentrations of sirukumab Part A & B: Immunogenicity: Serum anti-sirukumab antibodies
Eligibility
Minimum age: 50 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com Additional Information
Starting date: September 2015
Last updated: August 20, 2015
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