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

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

The primary purpose of this study is to identify an appropriate dose of study medication.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Clazakizumab; Drug: Placebo (Matching with Clazakizumab)

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1121
    • Local Institution
  • Buenos Aires, Argentina, 1426
    • Local Institution
  • Cordoba, Argentina, 5000
    • Local Institution
  • Tucuman, Argentina, 4000
    • Local Institution
  • Buenos Aires
    • Quilmes, Buenos Aires, Argentina, 1878
      • Local Institution
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 2B6
      • Cividino Medicine Professional Corporation
    • Mississauga, Ontario, Canada, L5M 2V8
      • Credit Valley Rheumatology
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • Dr. Latha Naik Medical Professional Corporation
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Poitiers, France, 86021
    • Local Institution
• Hungary
  • Budapest, Hungary, 1023
    • Local Institution
  • Debrecen, Hungary, 4012
    • Local Institution
  • Veszprem, Hungary, 8200
    • Local Institution
• Italy
  • Catanzaro, Italy, 88100
    • Local Institution
  • Firenze, Italy, 50139
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution
  • Pisa, Italy, 56126
    • Local Institution
• Japan
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608712
      • Local Institution
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 8078555
      • Local Institution
  • Hyogo
    • Kato-shi, Hyogo, Japan, 6731462
      • Local Institution
  • Nagano
    • Nagano-shi, Nagano, Japan, 3808582
      • Local Institution
  • Nagasaki
    • Sasebo-shi, Nagasaki, Japan, 8571195
      • Local Institution
  • Tokyo
    • Shinjuku-Ku, Tokyo, Japan, 1608582
      • Local Institution
    • Toshima-ku, Tokyo, Japan, 1708476
      • Local Institution
  • Wakayama
    • Nishimura, Wakayama, Japan, 6492211
      • Local Institution
• Mexico
  • Guadalajara, Mexico
    • Local Institution
  • San Luis Potosi, Mexico, 78200
    • Local Institution
  • Baja California
    • Tijuana, Baja California, Mexico, 22010
      • Local Institution
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution
    • Merida, Yucatan, Mexico, 97000
      • Local Institution
• South Africa
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7500
      • Local Institution
  • Western Cape
    • Stellenbosch, Western Cape, South Africa, 7600
      • Local Institution
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Rheumatology Associates Of North Alabama, P.C.
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Mercy Clinic Hot Springs Communities
  • California
    • Long Beach, California, United States, 90806
      • Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Minnesota
    • Eagan, Minnesota, United States, 55121
      • St. Paul Rheumatology, P.A.
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center For Rheumatology
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Joint and Muscle Medical Care and Research Institute (JMMCRI)
    • Greenville, North Carolina, United States, 27834
      • Physicians East, PA
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Rheumatic Disease Study Group
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research & Consulting, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Arthritis & Rheumatology Center of Oklahoma PLLC
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultants
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Rheumatology Consultants Pllc
    • Nashville, Tennessee, United States, 37203
      • Center For Inflammatory Disease
  • Washington
    • Seattle, Washington, United States, 98122
      • Seattle Rheumatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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 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. In Japan, Korea and Taiwan, a minimum dose of 7.5 mg per week is permitted. 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 (hs) CRP and/or ESR

Exclusion Criteria:

• Active serious infection
• History of or active tuberculosis (TB)
• Elevated liver function tests (LFTs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Clazakizumab (Dose # A) (Double-Blind); Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate	Drug: Clazakizumab; Other Names: BMS-945429
Experimental: Arm 2: Clazakizumab (Dose # B) (Double-Blind); Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate	Drug: Clazakizumab; Other Names: BMS-945429
Experimental: Arm 3: Clazakizumab (Dose # C) (Double-Blind); Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate	Drug: Clazakizumab; Other Names: BMS-945429
Experimental: Arm 4: Placebo matching with Clazakizumab (Double-Blind); Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate	Drug: Placebo (Matching with Clazakizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12	DAS28-CRP describes severity of rheumatoid arthritis. The components of the joint count assessment are shoulder, elbow, wrist, metacarpophalangeal joints 1 through 5, proximal interphalangeal joints 1 through 5, and the knee joints on the right and left sides, whereby the number of affected joints, tender and swollen, respectively, are counted. The formula used to calculate the score is: DAS28-CRP=0.56 \times \sqrt{TEN28} + 0.28 \times \sqrt{SW28} + 0.36 \times \ln(CRP+1) + 0.014 \times SA+0.96 with: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale between 0 and 100 ("0":no activity, "100": highest activity possible). DAS-CRP score range is 0.49 to 9.07 A DAS-CRP value >5.1 corresponds to a high disease activity A DAS-28 reduction by 0.6 represents a moderate improvement. A reduction >1.2 represents a major improvement	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American College of Rheumatology (ACR) 20/50/70 Response Rates	The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	At week 12
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12	CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76. CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity	Baseline and week 12
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12	SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86. 0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity	Baseline and week 12
Boolean Remission at Week 12	Boolean-based definition: At any time point, a patient must satisfy all of the following: TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)	At week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12	Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.	Baseline and Week 12
Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6	DAS28- ESR = Disease Activity Scores 28 based on erythrocyte sedimentation rate. A DAS28-ESR below 2.6 is interpreted as remission.	At week 12
Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6	DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.	At week 12

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: December 6, 2013
• First Submitted That Met QC Criteria: December 13, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): May 12, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: IM133-066; 2013-003780-65 (EudraCT Number)