Clinical trial NCT03600805: Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Giant Cell Arteritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Giant Cell Arteritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-07-26
Enrollment: 83
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Who Achieved Sustained Disease Remission at Week 52
timeFrame: At Week 52
measure: Percentage of Participants Who Achieved Sustained Disease Remission at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: Number of Participants With Achievement of Disease Remission up to Week 12: Week 52 Analysis Set
timeFrame: Up to Week 12
measure: Number of Participants With Achievement of Disease Remission up to Week 12: Intent-to-treat (ITT) Population
timeFrame: Up to Week 12
measure: Number of Participants With Absence of Disease Flare From Week 12 Through Week 52: Week 52 Analysis Set
timeFrame: From Week 12 through Week 52
measure: Number of Participants With Absence of Disease Flare From Week 12 Through Week 24: ITT Population
timeFrame: From Week 12 through Week 24
measure: Number of Participants With Normalization of C-Reactive Protein From Week 12 Through Week 52: Week 52 Analysis Set
timeFrame: From Week 12 through Week 52
measure: Number of Participants With Normalization of C-Reactive Protein (CRP) From Week 12 Through Week 24: ITT Population
timeFrame: From Week 12 through Week 24
measure: Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52: Week 52 Analysis Set
timeFrame: From Week 12 through Week 52
measure: Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 24: ITT Population
timeFrame: From Week 12 through Week 24
measure: Total Cumulative Corticosteroid (Including Prednisone) Dose
timeFrame: Up to Week 52
measure: Time to First Giant Cell Arteritis Disease Flare
timeFrame: Up to Week 52
measure: Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 24: ITT Population
timeFrame: At Week 24
measure: Composite Glucocorticoid Toxicity Index: Cumulative Worsening Score and Aggregate Improvement Score at Week 52
timeFrame: At Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose (i.e., up to Week 60)
measure: Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab
timeFrame: Pre-dose on Week 0 (Baseline), Weeks 2, 4, 12, 16, 24 and 52
measure: Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24
timeFrame: post-dose at Week 24
measure: Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
timeFrame: From Day 1 (Baseline) up to last dose date of study drug + 60 days (i.e., up to Week 60)
measure: Pharmacodynamics: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
measure: Pharmacodynamics: Change From Baseline in C-reactive Protein (CRP) Level at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
measure: Pharmacodynamics: Change From Baseline in Interleukin-6 (IL-6) at Weeks 2, 12, 24, and 52
timeFrame: Baseline, Weeks 2, 12, 24, and 52
measure: Pharmacodynamics: Change From Baseline in Soluble Interleukin-6 Receptor (sIL-6R) Level at Weeks 2, 12, 24, and 52
timeFrame: Baseline, Weeks 2, 12, 24, and 52
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Investigational Site Number 8400002
state: Florida
city: Gainesville
country: United States
facility: Investigational Site Number 8400017
state: Florida
city: Iowa City
country: United States
facility: Investigational Site Number 8400014
state: Iowa
city: Portland
country: United States
facility: Investigational Site Number 8400018
state: Oregon
city: Philadelphia
country: United States
facility: Investigational Site Number 8400019
state: Pennsylvania
city: Dallas
country: United States
facility: Investigational Site Number 8400011
state: Texas
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320001
city: Caba
country: Argentina
facility: Investigational Site Number 0320002
city: Camberwell
country: Australia
facility: Investigational Site Number 0360003
city: Clayton
country: Australia
facility: Investigational Site Number 0360006
city: Kogarah
country: Australia
facility: Investigational Site Number 0360001
city: Leuven
country: Belgium
facility: Investigational Site Number 0560001
city: Hamilton
country: Canada
facility: Investigational Site Number 1240007
city: Montreal
country: Canada
facility: Investigational Site Number 1240010
city: Rimouski
country: Canada
facility: Investigational Site Number 1240001
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1240005
city: Trois-Rivières
country: Canada
facility: Investigational Site Number 1240003
city: Zagreb
country: Croatia
facility: Investigational Site Number 1910001
city: Aarhus C
country: Denmark
facility: Investigational Site Number 2080002
city: Svendborg
country: Denmark
facility: Investigational Site Number 2080003
city: Tallinn
country: Estonia
facility: Investigational Site Number 2330001
city: Brest Cedex
country: France
facility: Investigational Site Number 2500005
city: Montivilliers
country: France
facility: Investigational Site Number 2500002
city: Montpellier
country: France
facility: Investigational Site Number 2500003
city: Mulhouse
country: France
facility: Investigational Site Number 2500007
city: Paris
country: France
facility: Investigational Site Number 2500001
city: Pessac
country: France
facility: Investigational Site Number 2500006
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
city: Dresden
country: Germany
facility: Investigational Site Number 2760002
city: Kirchheim Unter Teck
country: Germany
facility: Investigational Site Number 2760003
city: München
country: Germany
facility: Investigational Site Number 2760004
city: Tübingen
country: Germany
facility: Investigational Site Number 2760007
city: Debrecen
country: Hungary
facility: Investigational Site Number 3480001
city: Ashkelon
country: Israel
facility: Investigational Site Number 3760006
city: Haifa
country: Israel
facility: Investigational Site Number 3760004
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Rozzano
country: Italy
facility: Investigational Site Number 3800005
city: Den Haag
country: Netherlands
facility: Investigational Site Number 5280007
city: Leeuwarden
country: Netherlands
facility: Investigational Site Number 5280005
city: Sittard-Geleen
country: Netherlands
facility: Investigational Site Number 5280009
city: Venlo
country: Netherlands
facility: Investigational Site Number 5280001
city: Almada
country: Portugal
facility: Investigational Site Number 6200001
city: Aveiro
country: Portugal
facility: Investigational Site Number 6200005
city: Ponte De Lima
country: Portugal
facility: Investigational Site Number 6200004
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Ljubljana
country: Slovenia
facility: Investigational Site Number 7050001
city: Bilbao
country: Spain
facility: Investigational Site Number 7240010
city: La Coruña
country: Spain
facility: Investigational Site Number 7240011
city: Madrid
country: Spain
facility: Investigational Site Number 7240014
city: Sabadell
country: Spain
facility: Investigational Site Number 7240016
city: Santa Cruz De Tenerife
country: Spain
facility: Investigational Site Number 7240015
city: Uppsala
country: Sweden
facility: Investigational Site Number 7520001
city: Örebro
country: Sweden
facility: Investigational Site Number 7520003
city: St. Gallen
country: Switzerland
facility: Investigational Site Number 7560002
city: Aberdeen
country: United Kingdom
facility: Investigational Site Number 8260006
city: Gateshead
country: United Kingdom
facility: Investigational Site Number 8260004
city: Leeds
country: United Kingdom
facility: Investigational Site Number 8260003
city: Manchester
country: United Kingdom
facility: Investigational Site Number 8260005
city: Portsmouth
country: United Kingdom
facility: Investigational Site Number 8260011
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: