Evaluation of Efficacy and Safety of Sarilumab in Patients with GCA
- Conditions
- Giant Cell ArteritisMedDRA version: 20.0Level: LLTClassification code 10018250Term: Giant cell arteritisSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-002988-18-HR
- Lead Sponsor
- Sanofi-Aventis Recherche & Développement
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 508
-Diagnosis of giant cell arteritis (GCA) according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.
-New onset active disease or refractory active disease.
-At least one of the symptoms of GCA within 6 weeks of baseline.
-Either erythrocyte sedimentation rate (ESR) =30 mm/hour or C-reactive protein (CRP) =10 mg/L within 6 weeks of baseline.
-Receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 127
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 381
-Organ transplantation recipient (except corneas, unless it is within 3 months prior to baseline visit).
-Major ischemic event, unrelated to GCA, within 12 weeks of screening.
-Any prior use of the following therapies, for the treatment of GCA:
-Janus kinase inhibitor (e.g., tofacitinib) within 4 weeks of baseline.
-Cell-depletion agents (e.g., anti CD20) without evidence of recovery of B cells to baseline level.
-Abatacept within 8 weeks of baseline.
-Anakinra within 1 week of baseline.
-Tumor necrosis factor inhibitors within 2-8 weeks (etanercept within 2 weeks; infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or less than at least 5 half-lives have elapsed prior to baseline, whichever is longer.
-Therapeutic failure, including inadequate response or intolerance, or contraindication, to biological IL-6/(R) antagonist (prior experience with IL-6/(R) antagonist that was terminated for reasons unrelated to therapeutic failure at least 3 months before baseline is not exclusionary).
-Use of any alkylating agents including cyclophosphamide within 6 months of baseline.
-Use of immunosuppressant, such as hydroxychloroquine, cyclosporine, azathioprine,mycophenolate mofetil or leflunomide within 4 weeks of baseline. (Use of methotrexate (MTX) not exceeding 25 mg per week and have been stable for at least 3 months prior to baseline is not exclusionary).
-Concurrent use of systemic corticosteroids (CS) for conditions other than GCA.
-Use of IV CS at a dose equivalent to 100 mg of methylprednisolone or higher within 8 weeks of baseline for GCA therapy.
-Pregnant or breastfeeding woman.
-Patients with active or untreated latent tuberculosis.
-Patients with history of invasive opportunistic infections.
-Patients with fever associated with infection or chronic, persistent or recurring infections requiring active treatment.
-Patients with uncontrolled diabetes mellitus.
-Patients with non-healed or healing skin ulcers.
-Patients who received any live, attenuated vaccine within 3 months of baseline.
-Patients who are positive for hepatitis B, hepatitis C and/or HIV.
-Patients with a history of active or recurrent herpes zoster.
-Patients with a history of or prior articular or prosthetic joint infection.
-Prior or current history of malignancy.
-Patients who have had surgery within 4 weeks of screening or planned surgery during study.
-Patients with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of sarilumab in patients with giant cell arteritis (GCA) as assessed by the proportion of patients with sustained remission for sarilumab compared to placebo, in combination with a corticosteroid (CS) tapering course.;Secondary Objective: -To demonstrate the efficacy of sarilumab in patients with GCA compared to placebo, in combination with CS taper with regards to:<br> -Clinical responses (such as responses based on disease remission rates, time to first disease flare) over time.<br> -Cumulative CS (including prednisone) exposure.<br>-To assess the safety (including immunogenicity) and tolerability of sarilumab in patients with GCA.<br>-To measure sarilumab serum concentrations in patients with GCA.<br>-To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by glucocorticoid toxicity index (GTI).;Primary end point(s): Proportion of patients achieving sustained remission;Timepoint(s) of evaluation of this end point: Baseline to week 52
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Components of sustained remission (composite measure): Summary of the components of the sustained remission composite measure at Week 52 <br>2. Cumulative corticosteroid dose: Total cumulative corticosteroid (including prednisone) dose over 52 weeks<br>3. Time to first GCA flare: Duration of first GCA flare from clinical remission up to Week 52<br>4. Change in glucocorticoid toxicity index: Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52<br>5. Number of adverse events<br>6. Pharmacokinetic: Serum concentrations of sarilumab;Timepoint(s) of evaluation of this end point: 1. At Week 52<br>2. Up to Week 52<br>3. Up to Week 52<br>4. Up to Week 52<br>5. Up to Week 76<br>6. Up to Week 58