Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA

NCT03600805 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: EFC150682017-002988-18U1111-1200-2184
• Study Type: interventional
• Target: 83
• Locations: 20 countries
• Sites: 60

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).

Conditions

Giant Cell Arteritis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved Sustained Disease Remission at Week 52

  Disease remission was defined as resolution of signs and symptoms of giant cell arteries (GCA), and normalization of C-reactive protein (CRP) (\<10 mg/L). Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in corticosteroid \[CS\] dose due to GCA or elevation of erythrocyte sedimentation rate \[ESR\] attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 52, normalization of CRP (to \<10 mg/L, with absence of successive elevations to \>=10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52.

  At Week 52

• Percentage of Participants Who Achieved Sustained Disease Remission at Week 24

  Disease remission was defined as resolution of signs and symptoms of GCA, and normalization of CRP \<10 mg/L. Sustained remission was defined as meeting all of the following parameters: achievement of disease remission not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active GCA plus an increase in CS dose due to GCA, or elevation of ESR attributable to active GCA plus an increase in CS dose due to GCA) from Week 12 through Week 24, normalization of CRP (to \<10 mg/L, with an absence of successive elevations to \>=10 mg/L) from Week 12 through Week 24, and successful adherence to the prednisone taper from Week 12 through Week 24.

  At Week 24

Secondary Outcomes (20)

• Number of Participants With Achievement of Disease Remission up to Week 12: Week 52 Analysis Set

  Up to Week 12

• Number of Participants With Achievement of Disease Remission up to Week 12: Intent-to-treat (ITT) Population

  Up to Week 12

• Number of Participants With Absence of Disease Flare From Week 12 Through Week 52: Week 52 Analysis Set

  From Week 12 through Week 52

• Number of Participants With Absence of Disease Flare From Week 12 Through Week 24: ITT Population

  From Week 12 through Week 24

• Number of Participants With Normalization of C-Reactive Protein From Week 12 Through Week 52: Week 52 Analysis Set

  From Week 12 through Week 52

Study Arms (4)

Placebo+52 Week Taper

EXPERIMENTAL

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.

Drug: Sarilumab matching placebo; Drug: Prednisone; Drug: Prednisone matching placebo

Placebo+26 Week Taper

EXPERIMENTAL

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.

Drug: Sarilumab matching placebo; Drug: Prednisone; Drug: Prednisone matching placebo

Sarilumab 150mg q2w+26 Week Taper

PLACEBO COMPARATOR

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.

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

Sarilumab 200mg q2w+26 Week Taper

PLACEBO COMPARATOR

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.

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

Interventions

Sarilumab SAR153191 DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Sarilumab 150mg q2w+26 Week Taper; Sarilumab 200mg q2w+26 Week Taper

Sarilumab matching placebo DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo+26 Week Taper; Placebo+52 Week Taper

Prednisone DRUG

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

Placebo+26 Week Taper; Placebo+52 Week Taper; Sarilumab 150mg q2w+26 Week Taper; Sarilumab 200mg q2w+26 Week Taper

Prednisone matching placebo DRUG

Pharmaceutical form: capsules Route of administration: oral administration

Placebo+26 Week Taper; Placebo+52 Week Taper; Sarilumab 150mg q2w+26 Week Taper; Sarilumab 200mg q2w+26 Week Taper

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Use of any alkylating agents including cyclophosphamide within 6 months of baseline.
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (61)

Investigational Site Number 8400002

Boca Raton, Florida, 33486, United States

Location

Investigational Site Number 8400017

Gainesville, Florida, 32608, United States

Location

Investigational Site Number 8400014

Iowa City, Iowa, 52242, United States

Location

Investigational Site Number 8400018

Portland, Oregon, 97239, United States

Location

Investigational Site Number 8400019

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 8400011

Dallas, Texas, 75231, United States

Location

Investigational Site Number 0320001

Buenos Aires, C1015ABO, Argentina

Location

Investigational Site Number 0320002

Caba, C1181ACH, Argentina

Location

Investigational Site Number 0360003

Camberwell, 3124, Australia

Location

Investigational Site Number 0360006

Clayton, 3168, Australia

Location

Investigational Site Number 0360001

Kogarah, 2217, Australia

Location

Investigational Site Number 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number 1240007

Hamilton, L8N 4A6, Canada

Location

Investigational Site Number 1240010

Montreal, H4A 3T2, Canada

Location

Investigational Site Number 1240001

Rimouski, G5L 5T1, Canada

Location

Investigational Site Number 1240005

Sherbrooke, J1G 2E8, Canada

Location

Investigational Site Number 1240003

Trois-Rivières, G8Z 1Y2, Canada

Location

Investigational Site Number 1910001

Zagreb, 10000, Croatia

Location

Investigational Site Number 2080002

Aarhus C, 8000, Denmark

Location

Investigational Site Number 2080003

Svendborg, 5700, Denmark

Location

Investigational Site Number 2330001

Tallinn, 13419, Estonia

Location

Investigational Site Number 2500005

Brest, 29609, France

Location

Investigational Site Number 2500002

Montivilliers, 76290, France

Location

Investigational Site Number 2500003

Montpellier, 34295, France

Location

Investigational Site Number 2500007

Mulhouse, 68100, France

Location

Investigational Site Number 2500001

Paris, 75014, France

Location

Investigational Site Number 2500006

Pessac, 33604, France

Location

Investigational Site Number 2760001

Berlin, 13125, Germany

Location

Investigational Site Number 2760002

Dresden, 01307, Germany

Location

Investigational Site Number 2760003

Kirchheim unter Teck, 73230, Germany

Location

Investigational Site Number 2760004

München, 80336, Germany

Location

Investigational Site Number 2760007

Tübingen, 72076, Germany

Location

Investigational Site Number 3480001

Debrecen, 4032, Hungary

Location

Investigational Site Number 3760006

Ashkelon, 78278, Israel

Location

Investigational Site Number 3760004

Haifa, 34362, Israel

Location

Investigational Site Number 3800001

Milan, 20132, Italy

Location

Investigational Site Number 3800005

Rozzano, 20089, Italy

Location

Investigational Site Number 5280005

Leeuwarden, 8934 AD, Netherlands

Location

Investigational Site Number 5280009

Sittard-Geleen, 6162 BG, Netherlands

Location

Investigational Site Number 5280007

The Hague, 2545 CH, Netherlands

Location

Investigational Site Number 5280001

Venlo, 5912 BL, Netherlands

Location

Investigational Site Number 6200001

Almada, 2801-951, Portugal

Location

Investigational Site Number 6200005

Aveiro, 3810-501, Portugal

Location

Investigational Site Number 6200004

Ponte de Lima, 4990-041, Portugal

Location

Investigational Site Number 6430005

Kemerovo, 650000, Russia

Location

Investigational Site Number 6430002

Moscow, 115404, Russia

Location

Investigational Site Number 6430003

Moscow, 123182, Russia

Location

Investigational Site Number 7050001

Ljubljana, 1000, Slovenia

Location

Investigational Site Number 7240011

A Coruña, 15006, Spain

Location

Investigational Site Number 7240010

Bilbao, 48013, Spain

Location

Investigational Site Number 7240014

Madrid, 28046, Spain

Location

Investigational Site Number 7240016

Sabadell, 08208, Spain

Location

Investigational Site Number 7240015

Santa Cruz de Tenerife, 38320, Spain

Location

Investigational Site Number 7520003

Örebro, 701 85, Sweden

Location

Investigational Site Number 7520001

Uppsala, 751 85, Sweden

Location

Investigational Site Number 7560002

Sankt Gallen, 9007, Switzerland

Location

Investigational Site Number 8260006

Aberdeen, AB25 2ZN, United Kingdom

Location

Investigational Site Number 8260004

Gateshead, NE9 6SX, United Kingdom

Location

Investigational Site Number 8260003

Leeds, LS7 4SA, United Kingdom

Location

Investigational Site Number 8260005

Manchester, M13 9WL, United Kingdom

Location

Investigational Site Number 8260011

Portsmouth, PO6 3LY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37840134 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

sarilumab; Prednisone

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Study was prematurely discontinued due to protracted enrolment exacerbated by Covid-19 pandemic situation and not due to any safety issues from administration of sarilumab.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: November 20, 2018
• Primary Completion: November 24, 2020
• Study Completion: November 24, 2020
• Last Updated: March 28, 2022
• Results First Posted: January 14, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

SE (2); GB (5); AR (2); ES (5); FR (6); US (6); RU (3); SL (1); BE (1); PT (3); AU (3); DK (2); IL (2); IT (2); HU (1); DE (5); CA (5); NL (4); CR (1); CH (1)