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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 25 November 2019
Main ID:  EUCTR2016-001064-11-CZ
Date of registration: 31/03/2017
Prospective Registration: Yes
Primary sponsor: Nichi-Iko Pharmaceutical Co., Ltd.
Public title: Efficacy and safety study of Remicade® (infliximab) and NI-071 (a proposed infliximab biosimilar) for the treatment of patients with rheumatoid arthritis
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: 20/04/2017
Target sample size: 585
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001064-11
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 3
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Czech Republic Poland Puerto Rico Russian Federation Spain Ukraine United Kingdom United States
Contacts
Name: Biosimilar Development Department   
Address:  11th Floor, Sumitomo Fudosan Nihonbashi Bldg 103-0023 5-4 Nihonbashi-Honcho 1-chome, Chuo-ku Japan
Telephone:
Email: kenji-matsuyama@nichiiko.co.jp
Affiliation:  Nichi-Iko Pharmaceutical Co., Ltd.
Name: Biosimilar Development Department   
Address:  11th Floor, Sumitomo Fudosan Nihonbashi Bldg 103-0023 5-4 Nihonbashi-Honcho 1-chome, Chuo-ku Japan
Telephone:
Email: kenji-matsuyama@nichiiko.co.jp
Affiliation:  Nichi-Iko Pharmaceutical Co., Ltd.
Key inclusion & exclusion criteria
Inclusion criteria:
- Patients with a diagnosis of RA as defined by the 2010 ACR and European League Against Rheumatism (EULAR) classification criteria8
- Patients have active RA, as confirmed by the following criteria:
• =6 swollen joints and =6 tender joints at screening and baseline (28-
joint count), and
• Either CRP =0.7 mg/dL (=7.0 mg/L) or erythrocyte sedimentation rate
(ESR) =28 mm/h at screening
- Patients taking 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 with a body weight of =40 kg and =120 kg at screening
- Patients who are =18 and =75 years of age at screening
- Women of childbearing potential (WOCBP) and men (if their sexual partners are WOCBP) must use at least 1 highly effective form of birth control throughout the study and for 6 months after the last dose of study treatment. Highly effective methods of birth control include true sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk, in line with the preferred and usual lifestyle of the patient), surgery (bilateral tubal ligation or occlusion, vasectomized partner), progestogen-only or estrogen/progestogen hormonal contraceptive associated with inhibition of ovulation (oral, patch, injectable, implantable, or intravaginal), intrauterine device (IUD), or intrauterine hormone-releasing system (IUS). See Section 8.7 for a definition of WOCBP and a complete description of contraceptive requirements.

Refer to protocol for more inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 497
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 88

Exclusion criteria:
- Patients who have had prior treatment with infliximab
- Patients who have had prior treatment with more than 1 biological drug other than infliximab (e.g., adalimumab, rituximab, abatacept, etanercept) for RA either as part of clinical management or during a clinical study. Patients who have had prior treatment with more than 1 protein kinase inhibitor (e.g., tofacitinib) for RA either as part of clinical management or during a clinical study. Patients who have had prior treatment with 1 biological drug AND 1 protein kinase inhibitor are allowed in the study.
- Patients who have had prior treatment with a tumor necrosis factor alpha (TNF-a) inhibitor for RA who had lack of efficacy as per clinical judgment (primary failure). Primary failure is defined as never having achieved an adequate response, whereas secondary failure is the loss of response over time. Patients who have received prior treatment with no more than 1 biological DMARD and who have received not more than 1 prior TNF-a inhibitor (other than infliximab) and have failed it because of loss of efficacy (secondary failure) or intolerance (e.g., mild injection site reactions) are allowed in the study. Patients who have discontinued TNF-a inhibitors for RA (other than infliximab) because their insurance no longer covered the cost of treatment or they could no longer afford the cost or copays for the treatment are allowed in the study.
- Patients who had prior treatment with cyclophosphamide or other cytotoxic agents
- Patients with a concomitant or past history of autoimmune connective tissue diseases other than RA, for example, systemic lupus erythematosus, Sjogren's syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease
- Patients with a history of hypersensitivity to the components of NI-071 or mouse-derived protein (e.g., mouse, chimeric, and humanized antibody)
- Patients with the following concomitant or past history:
• Chronic or recurrent infectious disease (e.g., bronchiectasis, sinusitis)
• Demyelinating disease (e.g., multiple sclerosis)
• Presence of New York Heart Association (NYHA) Class III/IV heart failure (see Section 12.5)
• Lymphoproliferative disorder (e.g., Epstein-Barr virus [EBV]-related lymphoproliferative disorder, lymphoma, or leukemia) or myelodysplastic syndrome
• Cancer other than successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix
• Interstitial lung disease
- Patients with mycobacterial infection or opportunistic infection (e.g., cytomegalovirus infection or invasive fungal infection such as histoplasmosis, blastomycosis, or coccidiomycosis) or who have resided in or traveled to regions where such infections are prevalent within 6 months prior to the initial administration of the investigational drug
- Patients who received a live vaccine within 12 weeks prior to study dosing, or who plan to receive a live vaccine during the study period or within 6 months after the last dose of study treatment. (If received prior to study dosing, these patients may be re-screened after the appropriate washout period.)
- Female patients who are pregnant, wish to become pregnant, or are breastfeeding.
- Male patients who plan to donate


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Intervention(s)

Product Name: NI-071
Product Code: NI-071
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: NI-071
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Remicade
Product Name: Remicade
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Remicade
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: Stage 1 (Biosimilarity Stage)
Primary:
• To investigate the biosimilarity of NI-071 (proposed infliximab biosimilar) and US-licensed Remicade® (infliximab; Remicade-US) in terms of efficacy in patients with rheumatoid arthritis (RA) not adequately responding to methotrexate (MTX), by determining the percentages of patients achieving ACR20-CRP (a 20% improvement from baseline in the American College of Rheumatology [ACR] core set criteria using C-reactive protein [CRP] as the acute-phase reactant)
Stage 2 (Interchangeability Stage)
Primary:
• To investigate the interchangeability between NI-071 and Remicade-US by evaluating key pharmacokinetic (PK) parameters in each treatment group following treatment switches
Stage 3 (Safety Follow-up Stage)
Primary:
• To evaluate the safety of long-term treatment (follow-up through Week 62)

Primary end point(s): Clinical Efficacy
Primary endpoint:
• ACR20-CRP at Week 22

Pharmacokinetics
Primary endpoints:
• AUCtau and Cmax during the dosing interval of Weeks 46 to 54


Secondary Objective: Stage 1 (Biosimilarity Stage)
Secondary:
• To evaluate safety and immunogenicity of NI-071 and Remicade-US
• To evaluate efficacy based on other rates of improvement in the ACR criteria, on the DAS28 (disease activity score involving 28 joints) and the RAPID3 (routine assessment of patient index data 3), and on changes in health-related quality of life
Stage 2 (Interchangeability Stage)
Secondary:
• To evaluate the safety, efficacy, and immunogenicity of NI-071 and Remicade-US

Timepoint(s) of evaluation of this end point: Clinical Efficacy
• ACR20-CRP at Week 22

Pharmacokinetics
• AUCtau and Cmax during the dosing interval of Weeks 46 to 54



Please refer to the Schedule of Assessments in the protocol.
Secondary Outcome(s)

Secondary end point(s): Clinical Efficacy
Secondary endpoints:
• Change from baseline in DAS28-CRP and DAS28-ESR scores
• ACR20-CRP (at time points other than Week 22), ACR20-ESR, ACR50-CRP, ACR50-ESR, ACR70-CRP, and ACR70-ESR
• Change from baseline in each item of ACR core set
• Change from baseline in RAPID3 scores
• Change from baseline in SF-36 domain subscores and summary scores

Pharmacokinetics
Secondary endpoints:
• Minimum concentration (Cmin) and time at maximum concentration (tmax) during the dosing interval of Weeks 46 to 54

Timepoint(s) of evaluation of this end point: Please refer to the Schedule of Assessments in the protocol.
Secondary ID(s)
126520
2016-001064-11-GB
NI071F2
Source(s) of Monetary Support
Nichi-Iko Pharmaceutical Co., Ltd.
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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