NCT02990806|CompletedPhase 3ResultsDMCFDA Drug

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

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

Nichi-Iko Pharmaceutical Co., Ltd.ClinicalTrials.gov

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1 other identifier

NI071F2

Study Type

interventional

Target

683

Locations

8 countries

Sites

134

Timeline

RegisteredDec 2016

StartedJan 2017

CompletionMay 2019

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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

683

participants targeted

Target at P75+ for phase_3 rheumatoid-arthritis

Timeline

Completed

Started Jan 2017

Geographic Reach

8 countries

134 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.3 years study duration

First Submitted

Initial submission to the registry

November 21, 2016

Completed

22 days until next milestone

First Posted

Study publicly available on registry

December 13, 2016

Completed

1 month until next milestone

Study Start

First participant enrolled

January 19, 2017

Completed

2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 20, 2019

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2019

Completed

3.7 years until next milestone

Results Posted

Study results publicly available

January 25, 2023

Completed

Last Updated

January 30, 2023

Status Verified

January 1, 2023

Enrollment Period

2.3 years

First QC Date

November 21, 2016

Results QC Date

October 4, 2022

Last Update Submit

January 26, 2023

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR20-CRP) Response Rate at Week 22
ACR20 was defined as a dichotomous variable, for which a participant was defined as either a responder or a non-responder. Participant was defined as a responder if all of the following criteria are met: i) A 20% improvement from baseline in the tender/painful joint count. ii) A 20% improvement from baseline in the swollen joint count. iii) A 20% improvement from baseline in at least 3 of the following 5 variables: a) Participant global assessment of disease activity visual analog scale (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), b) Physician global assessment of disease activity (VAS) (0= no symptoms;100=severe symptoms), c) Participant pain assessment (VAS) (0=very good, no symptoms;100=very poor, severe symptoms), d) Health Assessment Questionnaire-Disability Index (HAQ-DI), total score ranging from 0-3 with lower scores meaning less disability, e) CRP.
At Week 22
Stage 2 and 3: Area Under the Serum Concentration-time Curve Interval (AUCtau) of NI-071 and Remicade US
AUCtau of NI-071 and Remicade US in stage 2 and 3 was reported. As this was an interchangeability study, the NI-071 and Remicade only were the comparators and then switch study showed same measurement in relationship to the non-switched participants. Hence, combined data was assessed and collected in participants from Remicade US to Switch Group.
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
Cmax of NI-071 and Remicade US was reported. As this was an interchangeability study, the NI-071 and Remicade only were the comparators and then switch study showed same measurement in relationship to the non-switched participants. Hence, combined data was assessed and collected in participants from Remicade US to Switch Group.
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 (32)

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
Baseline, 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
Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, 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
Baseline, Weeks 2, 6, 14, 18, and 22
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
Baseline, Weeks 26, 30, 34, 38, 42, 46, 50, 54, 58, and 62
Stage 1: Percentage of Participants Who Achieved 20 Percent (%) American College of Rheumatology C-reactive Protein (ACR-CRP) Response Rate
At Weeks 2, 6, 14, 18, and 22
+27 more secondary outcomes

Study Arms (4)

Stages 1, 2 and 3: NI-071 Group

EXPERIMENTAL

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).

Drug: NI-071

Stage 1: Remicade-US Group

EXPERIMENTAL

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

Drug: Remicade

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

EXPERIMENTAL

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).

Drug: Remicade

Stage 2 and Stage 3: Remicade US to Switch Group

EXPERIMENTAL

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).

Drug: NI-071Drug: Remicade

Interventions

NI-071DRUG

IV infusion.

Stage 2 and Stage 3: Remicade US to Switch GroupStages 1, 2 and 3: NI-071 Group

RemicadeDRUG

IV infusion.

Stage 1: Remicade-US GroupStage 2 and Stage 3: Remicade US to Remicade-US GroupStage 2 and Stage 3: Remicade US to Switch Group

Eligibility Criteria

Age18 Years - 75 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.