A Study of CNTO 136 (sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Patients with Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy

• Register: EUCTR
• Last refreshed on: 1 February 2016
• Main ID: EUCTR2010-022243-38-BE
• Date of registration: 06/09/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study of CNTO 136 (sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Patients with Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy
• Scientific title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Rheumatoid Arthritis Despite Anti-TNF-Alpha Therapy
• Date of first enrolment: 04/12/2012
• Target sample size: 840
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022243-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Croatia, France, Germany, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Russian Federation, Serbia, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
- Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
- Have moderately to severely active RA with at least 4 of 68 tender joints and 4 of 66 swollen joints, at screening and at baseline
- Have had anti-tumor necrosis factor (TNF)-alpha therapy and were unresponsive by 1 of the following 2 reasons: Lack of benefit to at least 1 anti-TNF-alpha biologic therapy, as assessed by the treating physician, after at least 12 weeks of etanercept, yisaipu, adalimumab, golimumab, or certolizumab pegol therapy and/or at least a 14-week dosage regimen (ie, at least 4 doses) of infliximab; Intolerance to at least 2 anti-TNF-alpha biologic therapies, as assessed by the treating physician, to etanercept, yisaipu, adalimumab, golimumab, certolizumab pegol, or infliximab or have documented intolerance to an anti-TNF-alpha agent as described above that precludes further administration of anti-TNF-alpha agents
- If using oral corticosteroids, must be on a stable dose equivalent to <=10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
- If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
- If using non-biologic DMARDs such as methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD
- C-reactive protein (CRP) >= 8.00 mg/L or erythrocyte sedimentation rate (ESR) >= 28 mm/hr at screening
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 733
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 107

Exclusion criteria:
- Has received infliximab, infliximab biosimilar, or golimumab IV within 8 weeks of the first study agent administration.
- Has received golimumab SC, adalimumab, or certolizumab pegol within 6 weeks of the first study agent administration.
- Has received etanercept or yisaipu within 4 weeks of the first study agent administration.
- Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy. Has used tocilizumab within 8 weeks of the first study agent administration.
- Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B-cell level caused by previous B-cell depletion therapy
- Has used anakinra within 1 week of first study agent administration
- Has used abatacept or any other biologic therapy for the treatment of RA within 8 weeks of the first study agent administration
- Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration
- Has received leflunomide within 24 months before the first study agent administration and has not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite
should be measured and found to be undetectable.
- Has a history of cyclophosphamide or cytotoxic agent use
- Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
- Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid Arthritis
MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Sirukumab
Product Code: CNTO136
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Sirukumab
Current Sponsor code: CNTO 136
Other descriptive name: Human anti-IL6 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50 -
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Sirukumab
Product Code: CNTO136
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Sirukumab
Current Sponsor code: CNTO 136
Other descriptive name: Human anti-IL6 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: The secondary objectives are to assess the following for sirukumab in subjects with active RA who are refractory to anti-TNF alpha agents:
-Safety
-Physical function
-Population pharmacokinetics
-Immunogenicity
-Pharmacodynamics

Primary end point(s): Proportion of patients with an ACR 20 response

Main Objective: The primary objective is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of RA in subjects with active RA who are refractory to an anti-TNF alpha agent.

Timepoint(s) of evaluation of this end point: Week 16

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Week 24
2. Week 24
3. Week 24
4. Week 0
5. 52 weeks
6. 52 weeks

Secondary end point(s): 1. Change from baseline in HAQ-DI
2. Proportion of patients with an ACR 50 response
3. Proportion of patients with DAS28 (CRP) remission
4. Pharmacogenetics (deoxyribonucleic acid [DNA]) Evaluations
5. Health economics avaluations
6. Plasma concentrations of Sirukumab

Secondary ID(s)

2010-022243-38-LT

CNTO136ARA3003

Source(s) of Monetary Support

Janssen Research and Development, LLC