Effect of SAR153191 (REGN88) With Methotrexate in Patients With Active Rheumatoid Arthritis Who Failed TNF-α Blockers

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Golimumab; Drug: Sarilumab; Drug: Placebo; Drug: methotrexate (MTX); Drug: Folic/folinic acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01217814

U1111-1115-3763 (Other Identifier)

2010-021020-94 (EudraCT Number)

ACT11575

Details and patient eligibility

About

Primary Objective:

• To demonstrate that sarilumab (SAR153191/REGN88) on top of methotrexate (MTX) was superior in efficacy to placebo for the relief of signs and symptoms of rheumatoid arthritis (RA), in participants with active RA who had failed up to 2 tumor necrosis factor-alpha (TNF-α) antagonists.

Secondary Objectives:

• To assess the safety of sarilumab;
• To document the pharmacokinetic profile of sarilumab.

Full description

The duration of the study period for each participant was approximately 22 weeks; including up to 4 weeks screening period, 12-week double-blind treatment period and 6-week safety follow-up period.

Participants who completed the 12-week treatment period were offered enrollment in a separate long-term extension study (LTS11210/NCT01146652).

Enrollment: 16 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of rheumatoid arthritis ≥6 months duration and American College of Rheumatology (ACR) Class I-III functional status at screening and baseline visits;

• Active disease defined as:

  • At least 6 of 68 tender joints and 6 of 66 swollen joints at screening and baseline visits, and
  • hs-C-Reactive Protein (hs-CRP) >10 g/L or Erythrocyte Sedimentation Rate (ESR) >28 mm/hr at screening visit;

• Continuous treatment with Methotrexate for at least 12 weeks and on stable dose (minimum 10 mg/week) for at least 6 weeks prior to the screening visit;

• Participant considered as Primary TNF-α blocker nonresponder. i.e.:

  • Appropriate for previous TNF-α blocker therapy
  • Lack of adequate clinical response after at least 3 months TNF-α blocker therapy with MTX or other synthetic disease modifying anti-rheumatic drug (DMARD) co-therapy.

Exclusion criteria

• Age <18 years or >75 years;
• Pregnant or breastfeeding woman or woman of childbearing potential, unwilling to utilize adequate contraception or not to become pregnant during the entire study;
• Fever (>38°C), or chronic, persistent, or recurring infection(s);
• History of demyelinating disease;
• Current underlying hepatobiliary disease.

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: Triple Blind

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16 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo 2 mL to match sarilumab once a week (qw) and 0.5 mL to match golimumab every 4 weeks (q4w) on top of MTX (15-25 mg) qw for 12 weeks.

Treatment:

Drug: Folic/folinic acid

Drug: Placebo

Drug: methotrexate (MTX)

Golimumab 50 mg

Active Comparator group

Description:

Golimumab 50 mg q4w and placebo (matched to sarilumab) qw on top of MTX (15-25 mg) qw for 12 weeks.

Treatment:

Drug: Golimumab

Drug: Folic/folinic acid

Drug: Placebo

Drug: methotrexate (MTX)

Sarilumab 150 mg

Experimental group

Description:

Sarilumab 150 mg qw and placebo (matched to golimumab) q4w on top of MTX (15-25 mg) qw for 12 weeks.

Treatment:

Drug: Sarilumab

Drug: Folic/folinic acid

Drug: Placebo

Drug: methotrexate (MTX)