A Phase 3 Study of NI-071 in Participants With Rheumatoid Arthritis (RADIANCE)

Nichi-Iko Pharmaceutical

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: NI-071; Drug: Remicade

Study type: Interventional

Funder types: Industry

Identifiers

NCT02990806

NI071F2

Details and patient eligibility

About

The purpose of this study was to demonstrate similarity of NI-071 (proposed biosimilar to infliximab) to US REMICADE® (reference product) in terms of safety and efficacy in participants with rheumatoid arthritis (RA) not adequately responding to methotrexate (MTX).

Enrollment: 683 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with a diagnosis of rheumatoid arthritis (RA) as defined by the 2010 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria.

• Patients have active RA, as confirmed by the following criteria:

  • ≥6 swollen joints and ≥6 tender joints at screening and baseline (28-joint count).
  • Either C-reactive protein (CRP) ≥0.7 mg/dL (≥7.0 mg/L) or erythrocyte sedimentation rate (ESR) ≥28 mm/h at screening.

• Patients taking methotrexate (MTX) (oral or parenteral) for at least 3 months prior to screening and at a stable dose of between 10 and 25 mg/week for at least 8 weeks. Concomitant folic/folinic acid at a dose of at least 5 mg/week is to be taken during the study; patients can start treatment with folic/folinic acid at screening if not already receiving it.

• If the patient is currently taking non-steroidal anti-inflammatory drugs (NSAIDs), the patient must be on a stable dose for at least 4 weeks prior to screening and during the study.

• Patients who are ≥18 and ≤75 years of age at screening.

Exclusion criteria

• Patients who are rated as Class IV according to the 1991 ACR revised criteria for classification of global functional status for RA.
• Patients who have received disease-modifying anti rheumatic drugs (DMARDs), other than MTX, within a period prior to screening shorter than the washout period appropriate to the pharmacodynamic profile of the specific drug.
• Patients who have received immunosuppressive drugs within 4 weeks prior to screening. Patients on a stable dose of oral corticosteroids (≤10 mg/day prednisone or equivalent) for ≥4 weeks prior to screening are permitted.
• Patients who have received intra-articular, intramuscular, intravenous, or epidural injection of corticosteroids within 4 weeks prior to screening.
• Patients who have received intra-articular sodium hyaluronate injections within 4 weeks prior to screening.
• Patients who have received surgical therapy for RA such as synovectomy or arthroplasty within 6 months prior to screening.
• Patients who have received arthrocentesis within 4 weeks prior to screening.
• Patients who have had prior treatment with infliximab.
• Patients who have had prior treatment with >1 biological drug or >1 protein kinase inhibitor for RA either as part of clinical management or during a clinical study.
• Patients who have had prior treatment with tumor necrosis factor alpha (TNF-α) inhibitors for RA who had lack of efficacy as per clinical judgment (primary failure). Patients who have discontinued TNF-α inhibitors for RA (other than infliximab) for any reason other than lack of efficacy are allowed.
• Presence of chronic or acute infection at screening, including positive result for active tuberculosis (TB).
• Patients with an acute infection requiring parenteral antibiotics within 4 weeks of study dosing or requiring oral/topical antibiotics within 2 weeks of study dosing.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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683 participants in 4 patient groups

Stages 1, 2 and 3: NI-071 Group

Experimental group

Description:

Participants received intravenous (IV) infusion of NI-071 at a dose of 3 milligrams/kilograms (mg/kg) at Weeks 0, 2, 6, 14 during stage 1 and at Weeks 22, 30, 38, 46, and 54 during stage 2. Participants were followed up to Week 62 (Stage 3).

Treatment:

Drug: NI-071

Stage 1: Remicade-US Group

Experimental group

Description:

Participants received IV infusion of Remicade-US (infliximab) at a dose of 3 mg/kg at Weeks 0, 2, 6, 14 during stage 1.

Treatment:

Drug: Remicade

Stage 2 and Stage 3: Remicade US to Remicade-US Group

Experimental group

Description:

Participants who received Remicade US during stage 1; were re-randomized during stage 2 to continue Remicade-US dose 3 mg/kg from Week 22 through Week 54 with every 8 weeks dosing intervals. Participants were followed up to Week 62 (Stage 3).

Treatment:

Drug: Remicade

Stage 2 and Stage 3: Remicade US to Switch Group

Experimental group

Description:

Participants who received Remicade US during stage 1; were re-randomized during stage 2 and received IV infusion of NI-071 at Week 22 followed by Remicade-US at Week 30, followed by NI-071 at Weeks 38, 46, and 54. Participants were followed up to week 62 (Stage 3).

Treatment:

Drug: NI-071

Drug: Remicade