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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 February 2023
• Main ID: NCT02990806
• Date of registration: 21/11/2016
• Prospective Registration: Yes
• Primary sponsor: Nichi-Iko Pharmaceutical Co., Ltd.
• Public title: A Phase 3 Study of NI-071 in Participants With Rheumatoid Arthritis (RADIANCE)
• Scientific title: A Randomized, Double-Blind, Multicenter, 3 Stage, Efficacy and Safety Study of NI-071 and US-Licensed Remicade® (Infliximab) for the Treatment of Patients With Rheumatoid Arthritis
• Date of first enrolment: January 19, 2017
• Target sample size: 683
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02990806
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Czechia, Poland, Puerto Rico, Russian Federation, Spain, Ukraine, United Kingdom, United States

Key inclusion & exclusion criteria

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-a)
inhibitors for RA who had lack of efficacy as per clinical judgment (primary failure).
Patients who have discontinued TNF-a 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: NI-071

Drug: Remicade

Primary Outcome(s)

Stage 2 and 3: Area Under the Serum Concentration-time Curve Interval (AUCtau) of NI-071 and Remicade US [Time Frame: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose]

Stage 2 and 3: Maximum Observed Serum Concentration (Cmax) of NI-071 and Remicade US [Time Frame: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose]

Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR20-CRP) Response Rate at Week 22 [Time Frame: At Week 22]

Secondary Outcome(s)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [Time Frame: Baseline up to Week 62]

Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 2, 6, 14, 18, and 22 [Time Frame: Baseline, Weeks 2, 6, 14, 18, and 22]

Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR [Time Frame: At Weeks 2, 6, 14, 18, and 22]

Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate [Time Frame: At Weeks 2, 6, 14, 18, and 22]

Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) [Time Frame: Baseline, Weeks 2, 6, 14, and 22]

Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate [Time Frame: At Weeks 2, 6, 14, 18, and 22]

Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 38 and 62 [Time Frame: Baseline, Weeks 38 and 62]

Stage 2 and 3: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 [Time Frame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies [Time Frame: At Weeks 30, 38, 46, 54, and 62]

Number of Participants With TEAEs of Special Interest [Time Frame: Baseline up to Week 62]

Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies [Time Frame: Baseline, Weeks 2, 6, 14, and 22]

Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22 [Time Frame: Baseline, Weeks 2, 6, 14, 18, and 22]

Stage 2 and 3: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 [Time Frame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 [Time Frame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA) [Time Frame: At Weeks 30, 38, 46, 54, and 62]

Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22 [Time Frame: Baseline, Weeks 2, 6, 14, 18, and 22]

Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate [Time Frame: At Weeks 2, 6, 14, 18, and 22]

Stage 2 and 3: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28) C-reactive Protein (CRP) at Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62 [Time Frame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Score for Physical and Mental Components at Weeks 14 and 22 [Time Frame: Baseline, Weeks 14 and 22]

Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22 [Time Frame: Baseline, Weeks 14 and 22]

Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR [Time Frame: At Weeks 2, 6, 14, 18, 22]

Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 38 and 62 [Time Frame: Baseline, Weeks 38 and 62]

Stage 1: Change From Baseline in the Disease Activity Score Based on 28 Joints (DAS28)-Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 6, 14, 18, and 22 [Time Frame: Baseline, Weeks 2, 6, 14, 18, and 22]

Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR) [Time Frame: At Weeks 2, 6, 14, 18, and 22]

Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Time to Reach the Maximum Serum Concentration (Tmax) of NI-071 and Remicade US [Time Frame: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose]

Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR [Time Frame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62]

Stage 2 and 3: Minimum Observed Serum Concentration (Cmin) of NI-071 and Remicade US [Time Frame: Week 46: Pre-dose, 1 hour after infusion, at end of infusion, at 4 hours and 24 hours after infusion and at Week 47, Week 48, Week 50, Week 52, and Week 54 post-dose]

Secondary ID(s)

NI071F2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 25/01/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02990806