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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02015520
Recruitment Status : Completed
First Posted : December 19, 2013
Results First Posted : April 19, 2021
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE December 6, 2013
First Posted Date  ICMJE December 19, 2013
Results First Submitted Date  ICMJE March 22, 2021
Results First Posted Date  ICMJE April 19, 2021
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE June 2012
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12 [ Time Frame: Baseline and 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2013)
Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) change from baseline at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • American College of Rheumatology (ACR) 20/50/70 Response Rates [ Time Frame: At week 12 ]
    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).
  • Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12 [ Time Frame: Baseline and 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
  • Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 [ Time Frame: Baseline and 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
  • Boolean Remission at Week 12 [ Time Frame: 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)
  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12 [ Time Frame: Baseline and 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.
  • Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6 [ Time Frame: At week 12 ]
    DAS28- ESR = Disease Activity Scores 28 based on erythrocyte sedimentation rate. A DAS28-ESR below 2.6 is interpreted as remission.
  • Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6 [ Time Frame: At week 12 ]
    DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2013)
  • American College of Rheumatology (ACR) 20/50/70 Responses [ Time Frame: At week 12 ]
  • Clinical Disease Activity Index (CDAI) [ Time Frame: At week 12 ]
  • Simplified Disease Activity Index (SDAI) [ Time Frame: At week 12 ]
  • Boolean Remission [ Time Frame: At week 12 ]
  • Health assessment questionnaire disability index (HAQ-DI) change from baseline at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ]
  • DAS28- Erythrocyte sedimentation rate (ESR) <2.6 [ Time Frame: At week 12 ]
  • DAS28-CRP<2.6 [ Time Frame: At week 12 ]
  • Safety based on adverse events (AEs), vital signs, physical examinations, safety lab values and immunogenicity during the double-blind period [ Time Frame: Up to week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis
Official Title  ICMJE 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
Brief Summary The primary purpose of this study is to identify an appropriate dose of study medication.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Clazakizumab
    Other Name: BMS-945429
  • Drug: Placebo (Matching with Clazakizumab)
Study Arms  ICMJE
  • Experimental: Arm 1: Clazakizumab (Dose # A) (Double-Blind)
    Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate
    Intervention: Drug: Clazakizumab
  • Experimental: Arm 2: Clazakizumab (Dose # B) (Double-Blind)
    Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate
    Intervention: Drug: Clazakizumab
  • Experimental: Arm 3: Clazakizumab (Dose # C) (Double-Blind)
    Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate
    Intervention: Drug: Clazakizumab
  • Experimental: Arm 4: Placebo matching with Clazakizumab (Double-Blind)
    Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate
    Intervention: Drug: Placebo (Matching with Clazakizumab)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2015)
143
Original Estimated Enrollment  ICMJE
 (submitted: December 13, 2013)
140
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Canada,   France,   Hungary,   Italy,   Japan,   Mexico,   South Africa,   United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT02015520
Other Study ID Numbers  ICMJE IM133-066
2013-003780-65 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party CSL Behring
Original Responsible Party Bristol-Myers Squibb
Current Study Sponsor  ICMJE CSL Behring
Original Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account CSL Behring
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP