Evaluation of Efficacy and Safety of Sarilumab in Patients with GCA

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-002988-18-DK
• Date of registration: 29/09/2018
• Prospective Registration: Yes
• Primary sponsor: Sanofi-Aventis Recherche & Développement
• Public title: Evaluation of Efficacy and Safety of Sarilumab in Patients with GCA
• Scientific title: A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis
• Date of first enrolment: 04/01/2019
• Target sample size: 508
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002988-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, Chile, Croatia, Denmark, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Portugal, Russian Federation, Slovenia, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Study Unit
• Affiliation: Sanofi Aventis Denmark A/S

• Name: Clinical Study Unit
• Affiliation: Sanofi Aventis Denmark A/S

Key inclusion & exclusion criteria

Inclusion criteria:
-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

Exclusion criteria:
-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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Giant Cell Arteritis
MedDRA version: 20.0 Level: LLT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 100000004866

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Kevzara ®
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SARILUMAB
Current Sponsor code: SAR153191
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Kevzara ®
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SARILUMAB
Current Sponsor code: SAR153191
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Cortancyl ® 5 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISONE
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Cortancyl ® 1 mg
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISONE
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Cortancyl ® 20 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Cortancyl ® 5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: -To demonstrate the efficacy of sarilumab in patients with GCA compared to placebo, in combination with CS taper with regards to:
-Clinical responses (such as responses based on disease remission rates, time to first disease flare) over time.
-Cumulative CS (including prednisone) exposure.
-To assess the safety (including immunogenicity) and tolerability of sarilumab in patients with GCA.
-To measure sarilumab serum concentrations in patients with GCA.
-To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by glucocorticoid toxicity index (GTI).

Timepoint(s) of evaluation of this end point: Baseline to week 52

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.

Primary end point(s): Proportion of patients achieving sustained remission

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. At Week 52
2. Up to Week 52
3. Up to Week 52
4. Up to Week 52
5. Up to Week 76
6. Up to Week 58

Secondary end point(s): 1. Components of sustained remission (composite measure): Summary of the components of the sustained remission composite measure at Week 52
2. Cumulative corticosteroid dose: Total cumulative corticosteroid (including prednisone) dose over 52 weeks
3. Time to first GCA flare: Duration of first GCA flare from clinical remission up to Week 52
4. Change in glucocorticoid toxicity index: Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52
5. Number of adverse events
6. Pharmacokinetic: Serum concentrations of sarilumab

Secondary ID(s)

2017-002988-18-DE

EFC15068

Source(s) of Monetary Support

Sanofi-Aventis Recherche & Développement

Ethics review

Status: Approved
Approval date: 04/01/2019
Contact: