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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02015520
• Other study ID #: IM133-066
• Secondary ID: 2013-003780-65
• Status: Completed
• Phase: Phase 2
• Start date: June 2012
• Est. completion date: June 2015

Study information

• Verified date: April 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: June 2015
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Clazakizumab

• Placebo (Matching with Clazakizumab)

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Quilmes	Buenos Aires
Argentina	Local Institution	Tucuman
Canada	Cividino Medicine Professional Corporation	Hamilton	Ontario
Canada	Credit Valley Rheumatology	Mississauga	Ontario
Canada	Dr. Latha Naik Medical Professional Corporation	Saskatoon	Saskatchewan
France	Local Institution	Bordeaux Cedex
France	Local Institution	Paris Cedex 14
France	Local Institution	Poitiers
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
Hungary	Local Institution	Veszprem
Italy	Local Institution	Catanzaro
Italy	Local Institution	Firenze
Italy	Local Institution	Napoli
Italy	Local Institution	Pisa
Japan	Local Institution	Chiba-shi	Chiba
Japan	Local Institution	Kato-shi	Hyogo
Japan	Local Institution	Kitakyushu-shi	Fukuoka
Japan	Local Institution	Nagano-shi	Nagano
Japan	Local Institution	Nishimura	Wakayama
Japan	Local Institution	Sasebo-shi	Nagasaki
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Toshima-ku	Tokyo
Mexico	Local Institution	Guadalajara
Mexico	Local Institution	Leon	Guanajuato
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Tijuana	Baja California
South Africa	Local Institution	Cape Town	Western CAPE
South Africa	Local Institution	Stellenbosch	Western Cape
United States	Albuquerque Center For Rheumatology	Albuquerque	New Mexico
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Low Country Rheumatology	Charleston	South Carolina
United States	Joint And Muscle Medical Care And Research Institute (Jmmcri)	Charlotte	North Carolina
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	St. Paul Rheumatology, P.A.	Eagan	Minnesota
United States	Physicians East, Pa	Greenville	North Carolina
United States	Mercy Clinic Hot Springs Communities	Hot Springs	Arkansas
United States	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama
United States	Rheumatology Consultants Pllc	Knoxville	Tennessee
United States	Physician Research Collaboration, Llc	Lincoln	Nebraska
United States	Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.	Long Beach	California
United States	Paramount Medical Research & Consulting, Llc	Middleburg Heights	Ohio
United States	Center For Inflammatory Disease	Nashville	Tennessee
United States	Arthritis & Rheumatology Center Of Oklahoma Pllc	Oklahoma City	Oklahoma
United States	Health Research Of Oklahoma	Oklahoma City	Oklahoma
United States	Desert Medical Advances	Palm Desert	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   BMS clinical trial educational resource