Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2013-003780-65-HU
• Date of registration: 21/01/2014
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb International Corporation
• Public title: Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis
• Scientific title: A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects with Moderate to Severe Active Rheumatoid Arthritis who have Experienced an Inadequate Response to TNF inhibitors Revised Protocol Number 02 incorporating Amendment 06 and Administrative Letter 02
• Date of first enrolment: 19/03/2014
• Target sample size: 230
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003780-65
• 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: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Argentina, Australia, Canada, France, Hungary, Italy, Japan, Mexico, South Africa, United States

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
• Diagnosis of active Rheumatoid Arthritis (RA) by standard criteria (American Rheumatism association (ARA) [1987] or American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) [2010]) at least 16 weeks prior to screening
• ACR global functional status class of 1 to 3
• Documented evidence of inadequate response to tumor necrosis factor (TNF) inhibitors.
• All subjects must have been receiving treatment with a minimum dose of 15 mg per week of Methotrexate for at least 12 weeks and at a stable dose for 28 days prior to screening. A dose as low as 10 mg Methotrexate is permitted if 15 mg could not be reached, due to toxicity. Additional treatment with Hydroxychloroquine or Chloroquine is permitted, if it is at
a dose approved for the treatment of RA and the dose has been stable for at least 28 days prior to screening
• Minimum of 6 swollen and 6 tender joints on a 66/68 joint count at screening and at baseline (Day 1)
• Elevated High-sensitivity CRP and/or ESR
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 184
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

Exclusion criteria:
• Active serious infection
• History of or active tuberculosis
• Elevated liver function tests


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid Arthritis
MedDRA version: 17.1 Level: LLT Classification code 10066578 Term: Progression of rheumatoid arthritis System Organ Class: 100000004859
MedDRA version: 17.1 Level: LLT Classification code 10060732 Term: Rheumatoid arthritis flare up System Organ Class: 100000004859

Intervention(s)

Product Name: CLAZAKIZUMAB
Product Code: BMS-945429
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: CLAZAKIZUMAB
CAS Number: 1236278-28-6
Current Sponsor code: BMS945429
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To compare the efficacy of clazakizumab versus placebo on a background of methotrexate as
assessed by change from baseline in DAS28-CRP at 12 weeks

Timepoint(s) of evaluation of this end point: Baseline (Day 1) and Week 12

Primary end point(s): Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) change from baseline at Week 12

Secondary Objective: 1) Assess the efficacy of clazakizumab on a background of methotrexate in reducing signs and symptoms of rheumatoid arthritis by measures such as ACR rates, remission rates, and DAS28-CRP < 2.6, over 12 weeks of treatment.
2) Assess the efficacy of clazakizumab on a background of methotrexate in improving physical function as determined by change from baseline in HAQ-DI at 12 weeks of treatment.
3) Assess the safety of clazakizumab on a background of methotrexate by assessment of Adverse Events (AEs) and laboratory parameters.
4) Characterize the pharmacokinetics, immunogenicity, pharmacodynamics and biomarker responses of different clazakizumab doses on a background of methotrexate.

Secondary Outcome(s)

Secondary end point(s): • American College of Rheumatology (ACR) 20/50/70 Responses
• Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Boolean Remission
• Health assessment questionnaire disability index (HAQ-DI) change from baseline at Week 12
• DAS28- Erythrocyte sedimentation rate (ESR) <2.6 and DAS28-CRP<2.6
• Adverse events (AEs), and immunogenicity during the double-blind period

Timepoint(s) of evaluation of this end point: • At week 12
• At week 12
• Baseline (Day 1) and Week 12
• At week 12
• Up to week 12

Secondary ID(s)

IM133-066

NCT02015520

2013-003780-65-IT

Source(s) of Monetary Support

Bristol-Myers Squibb International Corporation