Clinical trial NCT02990806: A Phase 3 Study of NI-071 in Participants 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Nichi-Iko Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-12-13
Enrollment: 683
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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-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.

Primary outcomes:
measure: Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR20-CRP) Response Rate at Week 22
timeFrame: At Week 22
measure: Stage 2 and 3: Area Under the Serum Concentration-time Curve Interval (AUCtau) of NI-071 and Remicade US
timeFrame: 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
measure: Stage 2 and 3: Maximum Observed Serum Concentration (Cmax) of NI-071 and Remicade US
timeFrame: 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 outcomes:
measure: 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
timeFrame: Baseline, Weeks 2, 6, 14, 18, and 22
measure: 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
timeFrame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: 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
timeFrame: Baseline, Weeks 2, 6, 14, 18, and 22
measure: 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
timeFrame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate
timeFrame: At Weeks 2, 6, 14, 18, and 22
measure: Stage 2 and 3: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 20% American College of Rheumatology (ACR20) Response Using Erythrocyte Sedimentation Rate (ESR)
timeFrame: At Weeks 2, 6, 14, 18, and 22
measure: 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)
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate
timeFrame: At Weeks 2, 6, 14, 18, and 22
measure: Stage 2 and 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology C-reactive Protein (ACR50-CRP) Response Rate
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR
timeFrame: At Weeks 2, 6, 14, 18, and 22
measure: Stage 2 and Stage 3: Percentage of Participants Who Achieved >=50% American College of Rheumatology (ACR50) Response Using ESR
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate
timeFrame: At Weeks 2, 6, 14, 18, and 22
measure: Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology C-reactive Protein (ACR70-CRP) Response Rate
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR
timeFrame: At Weeks 2, 6, 14, 18, 22
measure: Stage 2 and 3: Percentage of Participants Who Achieved >=70% American College of Rheumatology (ACR70) Response Using ESR
timeFrame: At Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 6, 14, 18, and 22
timeFrame: Baseline, Weeks 2, 6, 14, 18, and 22
measure: 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
timeFrame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Scores at Weeks 2, 6, 14, 18, and 22
timeFrame: Baseline, Weeks 2, 6, 14, 18, and 22
measure: 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
timeFrame: Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
measure: Stage 1: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 14 and 22
timeFrame: Baseline, Weeks 14 and 22
measure: Stage 2 and 3: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Total Score at Weeks 38 and 62
timeFrame: Baseline, Weeks 38 and 62
measure: 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
timeFrame: Baseline, Weeks 14 and 22
measure: 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
timeFrame: Baseline, Weeks 38 and 62
measure: Stage 2 and 3: Minimum Observed Serum Concentration (Cmin) of NI-071 and Remicade US
timeFrame: 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
measure: Stage 2 and 3: Time to Reach the Maximum Serum Concentration (Tmax) of NI-071 and Remicade US
timeFrame: 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
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to Week 62
measure: Number of Participants With TEAEs of Special Interest
timeFrame: Baseline up to Week 62
measure: Stage 1: Number of Participants With Positive Serum Anti-drug Antibodies (ADA)
timeFrame: Baseline, Weeks 2, 6, 14, and 22
measure: Stage 2 and 3: Number of Participants With Positive Serum Anti-drug Antibodies (ADA)
timeFrame: At Weeks 30, 38, 46, 54, and 62
measure: Stage 1: Number of Participants With Positive Serum Neutralizing Antibodies
timeFrame: Baseline, Weeks 2, 6, 14, and 22
measure: Stage 2 and 3: Number of Participants With Positive Serum Neutralizing Antibodies
timeFrame: At Weeks 30, 38, 46, 54, and 62
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Nichi-Iko Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: Nichi-Iko Investigational Site
state: California
city: Los Angeles
country: United States
facility: Nichi-Iko Investigational Site
state: California
city: Ventura
country: United States
facility: Nichi-Iko Investigational Site
state: California
city: Whittier
country: United States
facility: Nichi-Iko Investigational Site
state: California
city: Hamden
country: United States
facility: Nichi-Iko Investigational Site
state: Connecticut
city: Boca Raton
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Boynton Beach
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Brandon
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Doral
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Doral
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Miami
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Pinellas Park
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Nichi-Iko Investigational Site
state: Florida
city: West Palm Beach
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facility: Nichi-Iko Investigational Site
state: Florida
city: Decatur
country: United States
facility: Nichi-Iko Investigational Site
state: Georgia
city: Meridian
country: United States
facility: Nichi-Iko Investigational Site
state: Idaho
city: Lexington
country: United States
facility: Nichi-Iko Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Nichi-Iko Investigational Site
state: Kentucky
city: Worcester
country: United States
facility: Nichi-Iko Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Nichi-Iko Investigational Site
state: Michigan
city: Grand Rapids
country: United States
facility: Nichi-Iko Investigational Site
state: Michigan
city: Lansing
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facility: Nichi-Iko Investigational Site
state: Michigan
city: Tupelo
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facility: Nichi-Iko Investigational Site
state: Mississippi
city: Las Vegas
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facility: Nichi-Iko Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Nichi-Iko Investigational Site
state: Nevada
city: Freehold
country: United States
facility: Nichi-Iko Investigational Site
state: New Jersey
city: Durham
country: United States
facility: Nichi-Iko Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Nichi-Iko Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: Nichi-Iko Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Nichi-Iko Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Nichi-Iko Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Nichi-Iko Investigational Site
state: Ohio
city: Middleburg Heights
country: United States
facility: Nichi-Iko Investigational Site
state: Ohio
city: Oklahoma City
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facility: Nichi-Iko Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Nichi-Iko Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Nichi-Iko Investigational Site
state: Oklahoma
city: Duncansville
country: United States
facility: Nichi-Iko Investigational Site
state: Pennsylvania
city: Media
country: United States
facility: Nichi-Iko Investigational Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Nichi-Iko Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Nichi-Iko Investigational Site
state: South Carolina
city: Fort Mill
country: United States
facility: Nichi-Iko Investigational Site
state: South Carolina
city: Jackson
country: United States
facility: Nichi-Iko Investigational Site
state: Tennessee
city: Memphis
country: United States
facility: Nichi-Iko Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Baytown
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Beaumont
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Cypress
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: El Paso
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Galveston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Houston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Houston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Houston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Houston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Houston
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Nassau Bay
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Tomball
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Webster
country: United States
facility: Nichi-Iko Investigational Site
state: Texas
city: Chesapeake
country: United States
facility: Nichi-Iko Investigational Site
state: Virginia
city: Ostrava
country: Czechia
facility: Nichi-Iko Investigational Site
city: Praha 2
country: Czechia
facility: Nichi-Iko Investigational Site
city: Uherské Hradišté
country: Czechia
facility: Nichi-Iko Investigational Site
city: Zlin
country: Czechia
facility: Nichi-Iko Investigational Site
city: Białystok
country: Poland
facility: Nichi-Iko Investigational Site
city: Katowice
country: Poland
facility: Nichi-Iko Investigational Site
city: Lublin
country: Poland
facility: Nichi-Iko Investigational Site
city: Olsztyn
country: Poland
facility: Nichi-Iko Investigational Site
city: Poznań
country: Poland
facility: Nichi-Iko Investigational Site
city: Poznań
country: Poland
facility: Nichi-Iko Investigational Site
city: Toruń
country: Poland
facility: Nichi-Iko Investigational Site
city: Warsaw
country: Poland
facility: Nichi-Iko Investigational Site
city: Warszawa
country: Poland
facility: Nichi-Iko Investigational Site
city: Warszawa
country: Poland
facility: Nichi-Iko Investigational Site
city: Warszawa
country: Poland
facility: Nichi-Iko Investigational Site
city: Warszawa
country: Poland
facility: Nichi-Iko Investigational Site
city: Łódź
country: Poland
facility: Nichi-Iko Investigational Site
city: Łódź
country: Poland
facility: Nichi-Iko Investigational Site
city: Caguas
country: Puerto Rico
facility: Nichi-Iko Investigational Site
city: San Juan
country: Puerto Rico
facility: Nichi-Iko Investigational Site
city: Kemerovo
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Moscow
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Moscow
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Penza
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Petrozavodsk
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Ryazan
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Tomsk
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Vladimir
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Nichi-Iko Investigational Site
city: A Coruña
country: Spain
facility: Nichi-Iko Investigational Site
city: Barcelona
country: Spain
facility: Nichi-Iko Investigational Site
city: Barcelona
country: Spain
facility: Nichi-Iko Investigational Site
city: Santiago de Compostela
country: Spain
facility: Nichi-Iko Investigational Site
city: Santiago de Compostela
country: Spain
facility: Nichi-Iko Investigational Site
city: Sevilla
country: Spain
facility: Nichi-Iko Investigational Site
city: Kharkiv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Kharkiv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Kharkov
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Kyiv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Kyiv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Kyiv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Lviv
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Odesa
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Ternopil
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Vinnytsya
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Vinnytsya
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Vinnytsya
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Zhytomyr
country: Ukraine
facility: Nichi-Iko Investigational Site
city: Bury St Edmunds
country: United Kingdom
facility: Nichi-Iko Investigational Site
city: Gillingham
country: United Kingdom
facility: Nichi-Iko Investigational Site
city: Leicester
country: United Kingdom
facility: Nichi-Iko Investigational Site
city: Truro
country: United Kingdom
facility: Nichi-Iko Investigational Site
Study officials:
References: