Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Giant Cell Arteritis

Treatments: Drug: Prednisone; Drug: Sarilumab SAR153191; Drug: Sarilumab matching placebo; Drug: Prednisone matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03600805

U1111-1200-2184 (Other Identifier)

EFC15068

2017-002988-18 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To evaluate the efficacy of sarilumab in participants with giant cell arteritis (GCA) as assessed by the proportion of participants 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 participants 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 participants with GCA.
• To measure sarilumab serum concentrations in participants with GCA.
• To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by glucocorticoid toxicity index (GTI).

Full description

Study duration per participant was approximately 82 weeks, including an up to 6-week screening period, 52-week treatment period, and 24-week follow-up period.

Enrollment: 83 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Diagnosis of GCA according to European League Against Rheumatism/American College of Rheumatology 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 greater than or equal to (>=) 30 millimeter per hour or C-reactive protein >=10 mg per liter within 6 weeks of baseline.
• Received or were able to receive prednisone 20-60 mg/day for the treatment of active GCA.

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 had elapsed prior to baseline, whichever was longer.
• Therapeutic failure, including inadequate response or intolerance, or contraindication, to biological Interleukin 6 (IL-6) 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 was 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 had been stable for at least 3 months prior to baseline was not exclusionary).
• Concurrent use of systemic CS for conditions other than GCA.
• Use of intervascular CS at a dose equivalent to 100 mg of methylprednisolone or higher within 8 weeks of baseline for GCA therapy.
• Pregnant or breastfeeding woman.
• Participants with active or untreated latent tuberculosis.
• Participants with history of invasive opportunistic infections.
• Participants with fever associated with infection or chronic, persistent or recurring infections requiring active treatment.
• Participants with uncontrolled diabetes mellitus.
• Participants with non-healed or healing skin ulcers.
• Participants who received any live, attenuated vaccine within 3 months of baseline.
• Participants who are positive for hepatitis B, hepatitis C and/or HIV.
• Participants with a history of active or recurrent herpes zoster.
• Participants with a history of or prior articular or prosthetic joint infection.
• Prior or current history of malignancy.
• Participants who have had surgery within 4 weeks of screening or planned surgery during study.
• Participants with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation..

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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83 participants in 4 patient groups, including a placebo group

Placebo+52 Week Taper

Experimental group

Description:

Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.

Treatment:

Drug: Prednisone matching placebo

Drug: Sarilumab matching placebo

Drug: Prednisone

Placebo+26 Week Taper

Experimental group

Description:

Participants received sarilumab-matching placebo as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone matching placebo

Drug: Sarilumab matching placebo

Drug: Prednisone

Sarilumab 150mg q2w+26 Week Taper

Placebo Comparator group

Description:

Participants received sarilumab 150 milligrams (mg) as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone matching placebo

Drug: Sarilumab SAR153191

Drug: Prednisone

Sarilumab 200mg q2w+26 Week Taper

Placebo Comparator group

Description:

Participants received sarilumab 200 mg as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.

Treatment:

Drug: Prednisone matching placebo

Drug: Sarilumab SAR153191

Drug: Prednisone