Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA

NCT ID: NCT03600805

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-20
• Study Completion Date: 2020-11-24

Brief Summary

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).

Detailed 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.

Conditions

Giant Cell Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo+52 Week Taper

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.

Group Type: EXPERIMENTAL

Sarilumab matching placebo

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: tablets or capsules Route of administration: oral administration

Prednisone matching placebo

Intervention Type: DRUG

Pharmaceutical form: capsules Route of administration: oral administration

Placebo+26 Week Taper

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.

Group Type: EXPERIMENTAL

Sarilumab matching placebo

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: tablets or capsules Route of administration: oral administration

Prednisone matching placebo

Intervention Type: DRUG

Pharmaceutical form: capsules Route of administration: oral administration

Sarilumab 150mg q2w+26 Week Taper

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.

Group Type: PLACEBO_COMPARATOR

Sarilumab SAR153191

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: tablets or capsules Route of administration: oral administration

Prednisone matching placebo

Intervention Type: DRUG

Pharmaceutical form: capsules Route of administration: oral administration

Sarilumab 200mg q2w+26 Week Taper

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.

Group Type: PLACEBO_COMPARATOR

Sarilumab SAR153191

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

Pharmaceutical form: tablets or capsules Route of administration: oral administration

Prednisone matching placebo

Intervention Type: DRUG

Pharmaceutical form: capsules Route of administration: oral administration

Interventions

Sarilumab SAR153191

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Sarilumab matching placebo

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Prednisone

Pharmaceutical form: tablets or capsules Route of administration: oral administration

Intervention Type: DRUG

Prednisone matching placebo

Pharmaceutical form: capsules Route of administration: oral administration

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400002

Boca Raton, Florida, United States

Investigational Site Number 8400017

Gainesville, Florida, United States

Investigational Site Number 8400014

Iowa City, Iowa, United States

Investigational Site Number 8400018

Portland, Oregon, United States

Investigational Site Number 8400019

Philadelphia, Pennsylvania, United States

Investigational Site Number 8400011

Dallas, Texas, United States

Investigational Site Number 0320001

Buenos Aires, , Argentina

Investigational Site Number 0320002

Caba, , Argentina

Investigational Site Number 0360003

Camberwell, , Australia

Investigational Site Number 0360006

Clayton, , Australia

Investigational Site Number 0360001

Kogarah, , Australia

Investigational Site Number 0560001

Leuven, , Belgium

Investigational Site Number 1240007

Hamilton, , Canada

Investigational Site Number 1240010

Montreal, , Canada

Investigational Site Number 1240001

Rimouski, , Canada

Investigational Site Number 1240005

Sherbrooke, , Canada

Investigational Site Number 1240003

Trois-Rivières, , Canada

Investigational Site Number 1910001

Zagreb, , Croatia

Investigational Site Number 2080002

Aarhus C, , Denmark

Investigational Site Number 2080003

Svendborg, , Denmark

Investigational Site Number 2330001

Tallinn, , Estonia

Investigational Site Number 2500005

Brest, , France

Investigational Site Number 2500002

Montivilliers, , France

Investigational Site Number 2500003

Montpellier, , France

Investigational Site Number 2500007

Mulhouse, , France

Investigational Site Number 2500001

Paris, , France

Investigational Site Number 2500006

Pessac, , France

Investigational Site Number 2760001

Berlin, , Germany

Investigational Site Number 2760002

Dresden, , Germany

Investigational Site Number 2760003

Kirchheim unter Teck, , Germany

Investigational Site Number 2760004

München, , Germany

Investigational Site Number 2760007

Tübingen, , Germany

Investigational Site Number 3480001

Debrecen, , Hungary

Investigational Site Number 3760006

Ashkelon, , Israel

Investigational Site Number 3760004

Haifa, , Israel

Investigational Site Number 3800001

Milan, , Italy

Investigational Site Number 3800005

Rozzano, , Italy

Investigational Site Number 5280005

Leeuwarden, , Netherlands

Investigational Site Number 5280009

Sittard-Geleen, , Netherlands

Investigational Site Number 5280007

The Hague, , Netherlands

Investigational Site Number 5280001

Venlo, , Netherlands

Investigational Site Number 6200001

Almada, , Portugal

Investigational Site Number 6200005

Aveiro, , Portugal

Investigational Site Number 6200004

Ponte de Lima, , Portugal

Investigational Site Number 6430005

Kemerovo, , Russia

Investigational Site Number 6430002

Moscow, , Russia

Investigational Site Number 6430003

Moscow, , Russia

Investigational Site Number 7050001

Ljubljana, , Slovenia

Investigational Site Number 7240011

A Coruña, , Spain

Investigational Site Number 7240010

Bilbao, , Spain

Investigational Site Number 7240014

Madrid, , Spain

Investigational Site Number 7240016

Sabadell, , Spain

Investigational Site Number 7240015

Santa Cruz de Tenerife, , Spain

Investigational Site Number 7520003

Örebro, , Sweden

Investigational Site Number 7520001

Uppsala, , Sweden

Investigational Site Number 7560002

Sankt Gallen, , Switzerland

Investigational Site Number 8260006

Aberdeen, , United Kingdom

Investigational Site Number 8260004

Gateshead, , United Kingdom

Investigational Site Number 8260003

Leeds, , United Kingdom

Investigational Site Number 8260005

Manchester, , United Kingdom

Investigational Site Number 8260011

Portsmouth, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Croatia; Denmark; Estonia; France; Germany; Hungary; Israel; Italy; Netherlands; Portugal; Russia; Slovenia; Spain; Sweden; Switzerland; United Kingdom

References

Schmidt WA, Dasgupta B, Sloane J, Giannelou A, Xu Y, Unizony SH, Mackie SL, Gonzalez-Gay MA, Spiera R, Warrington KJ, Villiger PM, Nivens MC, Akinlade B, Lin Y, Buttgereit F, Stone JH. A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis. Arthritis Res Ther. 2023 Oct 16;25(1):199. doi: 10.1186/s13075-023-03177-6.

Reference Type: DERIVED

PMID: 37840134 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002988-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1200-2184

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15068

Identifier Type: -

Identifier Source: org_study_id