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

• ClinicalTrials.gov Identifier: NCT02990806
• Recruitment Status: Completed
• First Posted: December 13, 2016
• Last Update Posted: May 18, 2020
• Sponsor: Nichi-Iko Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Nichi-Iko Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: November 21, 2016
• First Posted Date: December 13, 2016
• Last Update Posted Date: May 18, 2020
• Study Start Date: December 2016
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2016)

• 20% improvement from baseline in the American College of Rheumatology (ACR) core set criteria using C-reactive protein (CRP) (ACR20-CRP) [ Time Frame: At Week 22 ]
• Area under the plasma concentration-time curve for a dosing interval (AUCtau) [ Time Frame: During the dosing interval of Weeks 46 to 54 ]
• Maximum concentration (Cmax) [ Time Frame: During the dosing interval of Weeks 46 to 54 ]
• Long-term safety (Incidence of Adverse Events, Incidence of Anti-Drug Antibodies (ADA), etc.) [ Time Frame: Through study completion ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 8, 2016)

• ACR20-CRP (at time points other than Week 22) [ Time Frame: up to Week 62 ]
• 20% improvement from baseline in the ACR core set criteria using erythrocyte sedimentation rate (ESR) (ACR20-ESR) [ Time Frame: up to Week 62 ]
• 50% improvement from baseline in the ACR core set criteria using CRP (ACR50-CRP) [ Time Frame: up to Week 62 ]
• 50% improvement from baseline in the ACR core set criteria using ESR (ACR50-ESR) [ Time Frame: up to Week 62 ]
• 70% improvement from baseline in the ACR core set criteria using CRP (ACR70-CRP) [ Time Frame: up to Week 62 ]
• 70% improvement from baseline in the ACR core set criteria using ESR (ACR70-ESR) [ Time Frame: up to Week 62 ]
• Change from baseline in the disease activity score based on 28 joints (DAS28) [ Time Frame: up to Week 62 ]
• Change from baseline in the routine assessment of patient index data 3 (RAPID3) scores [ Time Frame: up to Week 62 ]
• Change from baseline in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [ Time Frame: up to Week 62 ]
• Minimum concentration (Cmin) [ Time Frame: During the dosing interval of Weeks 46 to 54 ]
• Time at maximum concentration (tmax) [ Time Frame: During the dosing interval of Weeks 46 to 54 ]

• 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: A Phase 3 Study of NI-071 in Patients With Rheumatoid Arthritis (RADIANCE)
• Official 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
• Brief Summary: The purpose of this study is to demonstrate similarity of NI-071 (proposed biosimilar to infliximab) to US REMICADE® (reference product) in terms of safety and efficacy in patients with rheumatoid arthritis (RA) not adequately responding to methotrexate (MTX).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis (RA)

Intervention

• Biological: NI-071
  20 ml vial containing 100 mg for a final reconstitution volume of 10 mg/mL
  Other Name: Proposed infliximab biosimilar
• Biological: Infliximab
  20 ml vial containing 100 mg for a final reconstitution volume of 10 mg/mL
  Other Name: Remicade

Study Arms

• Experimental: NI-071
  Proposed biosimilar
  Intervention: Biological: NI-071
• Active Comparator: Infliximab
  Reference product
  Intervention: Biological: Infliximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 4, 2019): 683
• Original Estimated Enrollment (submitted: December 8, 2016): 585
• Actual Study Completion Date: May 2019
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with a diagnosis of rheumatoid arthritis (RA) as defined by the 2010 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Poland, Puerto Rico, Russian Federation, Spain, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT02990806
• Other Study ID Numbers: NI071F2; 2016-001064-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Nichi-Iko Pharmaceutical Co., Ltd.
• Study Sponsor: Nichi-Iko Pharmaceutical Co., Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nichi-Iko Pharmaceutical Co., Ltd.
• Verification Date: May 2020