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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Clazakizumab
Placebo (Matching with Clazakizumab)
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Rheumatology Associates Of North Alabama, P.C.
  • Mercy Clinic Hot Springs Communities
  • Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
  • Desert Medical Advances
  • Sarasota Arthritis Research Center
  • Clinical Pharmacology Study Group
  • St. Paul Rheumatology, P.A.
  • Physician Research Collaboration, Llc
  • Albuquerque Center For Rheumatology
  • Albuquerque Clinical Trials
  • Joint And Muscle Medical Care And Research Institute (Jmmcri)
  • Physicians East, Pa
  • Cincinnati Rheumatic Disease Study Group
  • Paramount Medical Research & Consulting, Llc
  • Arthritis & Rheumatology Center Of Oklahoma Pllc
  • Health Research Of Oklahoma
  • Healthcare Research Consultants
  • Low Country Rheumatology
  • Rheumatology Consultants Pllc
  • Center For Inflammatory Disease
  • Seattle Rheumatology Associates
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Cividino Medicine Professional Corporation
  • Credit Valley Rheumatology
  • Dr. Latha Naik Medical Professional Corporation
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1: Clazakizumab (Dose # A) (Double-Blind)

Arm 2: Clazakizumab (Dose # B) (Double-Blind)

Arm 3: Clazakizumab (Dose # C) (Double-Blind)

Arm 4: Placebo matching with Clazakizumab (Double-Blind)

Arm Description

Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate

Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate

Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate

Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
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
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
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)
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.
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.
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.

Full Information

First Posted
December 6, 2013
Last Updated
April 16, 2021
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT02015520
Brief Title
Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 2012 (Actual)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
143 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Clazakizumab (Dose # A) (Double-Blind)
Arm Type
Experimental
Arm Description
Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate
Arm Title
Arm 2: Clazakizumab (Dose # B) (Double-Blind)
Arm Type
Experimental
Arm Description
Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate
Arm Title
Arm 3: Clazakizumab (Dose # C) (Double-Blind)
Arm Type
Experimental
Arm Description
Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate
Arm Title
Arm 4: Placebo matching with Clazakizumab (Double-Blind)
Arm Type
Experimental
Arm Description
Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate
Intervention Type
Drug
Intervention Name(s)
Clazakizumab
Other Intervention Name(s)
BMS-945429
Intervention Type
Drug
Intervention Name(s)
Placebo (Matching with Clazakizumab)
Primary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
Description
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
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
American College of Rheumatology (ACR) 20/50/70 Response Rates
Description
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).
Time Frame
At week 12
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
Description
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
Time Frame
Baseline and week 12
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
Description
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
Time Frame
Baseline and week 12
Title
Boolean Remission at Week 12
Description
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)
Time Frame
At week 12
Title
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12
Description
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.
Time Frame
Baseline and Week 12
Title
Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6
Description
DAS28- ESR = Disease Activity Scores 28 based on erythrocyte sedimentation rate. A DAS28-ESR below 2.6 is interpreted as remission.
Time Frame
At week 12
Title
Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6
Description
DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Time Frame
At week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Rheumatology Associates Of North Alabama, P.C.
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Mercy Clinic Hot Springs Communities
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Facility Name
Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
Sarasota Arthritis Research Center
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Clinical Pharmacology Study Group
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
St. Paul Rheumatology, P.A.
City
Eagan
State/Province
Minnesota
ZIP/Postal Code
55121
Country
United States
Facility Name
Physician Research Collaboration, Llc
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Albuquerque Center For Rheumatology
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Albuquerque Clinical Trials
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Joint And Muscle Medical Care And Research Institute (Jmmcri)
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Physicians East, Pa
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Cincinnati Rheumatic Disease Study Group
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Paramount Medical Research & Consulting, Llc
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
Arthritis & Rheumatology Center Of Oklahoma Pllc
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Health Research Of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Healthcare Research Consultants
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Facility Name
Low Country Rheumatology
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Rheumatology Consultants Pllc
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
Center For Inflammatory Disease
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Seattle Rheumatology Associates
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Local Institution
City
Quilmes
State/Province
Buenos Aires
ZIP/Postal Code
1878
Country
Argentina
Facility Name
Local Institution
City
Buenos Aires
ZIP/Postal Code
1121
Country
Argentina
Facility Name
Local Institution
City
Buenos Aires
ZIP/Postal Code
1426
Country
Argentina
Facility Name
Local Institution
City
Cordoba
ZIP/Postal Code
5000
Country
Argentina
Facility Name
Local Institution
City
Tucuman
ZIP/Postal Code
4000
Country
Argentina
Facility Name
Cividino Medicine Professional Corporation
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 2B6
Country
Canada
Facility Name
Credit Valley Rheumatology
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5M 2V8
Country
Canada
Facility Name
Dr. Latha Naik Medical Professional Corporation
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7K 3H3
Country
Canada
Facility Name
Local Institution
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Local Institution
City
Paris Cedex 14
ZIP/Postal Code
75679
Country
France
Facility Name
Local Institution
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Local Institution
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Local Institution
City
Debrecen
ZIP/Postal Code
4012
Country
Hungary
Facility Name
Local Institution
City
Veszprem
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Local Institution
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Facility Name
Local Institution
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Local Institution
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Local Institution
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Local Institution
City
Chiba-shi
State/Province
Chiba
ZIP/Postal Code
2608712
Country
Japan
Facility Name
Local Institution
City
Kitakyushu-shi
State/Province
Fukuoka
ZIP/Postal Code
8078555
Country
Japan
Facility Name
Local Institution
City
Kato-shi
State/Province
Hyogo
ZIP/Postal Code
6731462
Country
Japan
Facility Name
Local Institution
City
Nagano-shi
State/Province
Nagano
ZIP/Postal Code
3808582
Country
Japan
Facility Name
Local Institution
City
Sasebo-shi
State/Province
Nagasaki
ZIP/Postal Code
8571195
Country
Japan
Facility Name
Local Institution
City
Shinjuku-Ku
State/Province
Tokyo
ZIP/Postal Code
1608582
Country
Japan
Facility Name
Local Institution
City
Toshima-ku
State/Province
Tokyo
ZIP/Postal Code
1708476
Country
Japan
Facility Name
Local Institution
City
Nishimura
State/Province
Wakayama
ZIP/Postal Code
6492211
Country
Japan
Facility Name
Local Institution
City
Tijuana
State/Province
Baja California
ZIP/Postal Code
22010
Country
Mexico
Facility Name
Local Institution
City
Leon
State/Province
Guanajuato
ZIP/Postal Code
37000
Country
Mexico
Facility Name
Local Institution
City
Merida
State/Province
Yucatan
ZIP/Postal Code
97000
Country
Mexico
Facility Name
Local Institution
City
Merida
State/Province
Yucatan
ZIP/Postal Code
97070
Country
Mexico
Facility Name
Local Institution
City
Guadalajara
Country
Mexico
Facility Name
Local Institution
City
San Luis Potosi
ZIP/Postal Code
78200
Country
Mexico
Facility Name
Local Institution
City
Cape Town
State/Province
Western CAPE
ZIP/Postal Code
7500
Country
South Africa
Facility Name
Local Institution
City
Stellenbosch
State/Province
Western Cape
ZIP/Postal Code
7600
Country
South Africa

12. IPD Sharing Statement

Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

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

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