Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA

• ClinicalTrials.gov Identifier: NCT03600805
• Recruitment Status: Terminated
• First Posted: July 26, 2018
• Last Update Posted: December 28, 2020
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: July 17, 2018
• First Posted Date: July 26, 2018
• Last Update Posted Date: December 28, 2020
• Actual Study Start Date: November 20, 2018
• Actual Primary Completion Date: November 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2018)

Proportion of patients with sustained remission [ Time Frame: At Week 52 ]

Proportion of patients achieving sustained remission at Week 52.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 17, 2018)

• Components of sustained remission (composite measure) [ Time Frame: At Week 52 ]
  Summary of the components of the sustained remission composite measure at Week 52
• Cumulative corticosteroid dose [ Time Frame: Up to Week 52 ]
  Total cumulative corticosteroid (including prednisone) dose over 52 weeks
• Time to first GCA flare [ Time Frame: Up to Week 52 ]
  Duration of first GCA flare from clinical remission up to Week 52
• Change in glucocorticoid toxicity index [ Time Frame: Up to Week 52 ]
  Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52
• Adverse events [ Time Frame: Up to Week 76 ]
  Number of adverse events
• Pharmacokinetic [ Time Frame: Up to Week 58 ]
  Serum concentrations of sarilumab

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

Brief Summary

Primary 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.

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).

• Detailed Description: Study duration per participant is approximately 82 weeks, including an up to 6-week screening period, 52-week treatment period, and 24-week follow-up period.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Giant Cell Arteritis

Intervention

• Drug: Sarilumab SAR153191
  Pharmaceutical form:solution for injection Route of administration: subcutaneous
• Drug: Sarilumab matching placebo
  Pharmaceutical form:solution for injection Route of administration: subcutaneous
• Drug: Prednisone
  Pharmaceutical form:tablets or capsules Route of administration: oral administration
• Drug: Prednisone matching placebo
  Pharmaceutical form:capsules Route of administration: oral administration

Study Arms

• Experimental: Group A
  Sarilumab dose 1, once every 2 weeks plus 26-week prednisone taper regimen
  Interventions:

  • Drug: Sarilumab SAR153191
  • Drug: Prednisone
  • Drug: Prednisone matching placebo
• Experimental: Group B
  Sarilumab dose 2, once every 2 weeks plus 26-week prednisone taper regimen
  Interventions:

  • Drug: Sarilumab SAR153191
  • Drug: Prednisone
  • Drug: Prednisone matching placebo
• Placebo Comparator: Group C
  Sarilumab matching placebo once every 2 weeks plus prednisone regimen 26 weeks
  Interventions:

  • Drug: Sarilumab matching placebo
  • Drug: Prednisone
  • Drug: Prednisone matching placebo
• Placebo Comparator: Group D
  Sarilumab matching placebo once every 2 weeks plus prednisone regimen 52 weeks
  Interventions:

  • Drug: Sarilumab matching placebo
  • Drug: Prednisone
  • Drug: Prednisone matching placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 23, 2020): 83
• Original Estimated Enrollment (submitted: July 17, 2018): 360
• Actual Study Completion Date: November 24, 2020
• Actual Primary Completion Date: November 24, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria :

• Diagnosis of giant cell arteritis (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 ≥30 mm/hour or C-reactive protein ≥10 mg/L within 6 weeks of baseline.
• Receiving or 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 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..

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Croatia, Denmark, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Portugal, Russian Federation, Slovenia, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT03600805
• Other Study ID Numbers: EFC15068; 2017-002988-18 ( EudraCT Number ); U1111-1200-2184 ( Other Identifier: UTN )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: December 2020