Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase IIB , Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo/Active Controlled Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection With or Without Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Methotrexate.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01373151
• Other study ID #: IM133-001
• Secondary ID: 2010-023956-99
• Status: Completed
• Phase: Phase 2
• Start date: June 2011
• Est. completion date: June 2015

Study information

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

Clinical Trial Summary

The purpose of this study is to determine the effective dose of BMS-945429 in subjects with inadequate response to Methotrexate in the treatment of moderate to severe Rheumatoid Arthritis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: June 2015
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Inadequate response to Methotrexate
• Must have been taking Methotrexate for at least 3 months at a minimal weekly dose of at least 15 mg and stable dose for 4 weeks prior to randomization
• American College of Rheumatology (ACR) global function status class 1-3
• Minimum of 6 swollen and 6 tender joints with evidence of synovitis in at least 1 hand or wrist
• High sensitivity C-reactive protein (hsCRP) = 0.8 mg/dL

Exclusion Criteria:

• Previously received or currently receiving concomitant biologic therapy

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• BMS-945429 Placebo
Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only

Biological:
• BMS-945429
Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only
• BMS-945429
Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks
• BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48
• BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks

Drug:
• Methotrexate
Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only
• Methotrexate
Tablets, Oral, 15 mg, Weekly, 48 weeks
• Methotrexate Placebo
Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
• Methotrexate
Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only
• Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
• Adalimumab
Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Rosario	Santa FE
Argentina	Local Institution	San Juan
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Hasselt
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Juiz De Fora	Minas Gerais
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Quebec
Canada	Centre De Recherche Musculo-Squelettique	Trois-rivieres	Quebec
Czechia	Local Institution	Praha 2
Czechia	Local Institution	Praha 4
France	Local Institution	Bordeaux Cedex
France	Local Institution	Chambray Les Tours
France	Local Institution	Strasbourg Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Koeln
Germany	Local Institution	Leipzig
Germany	Local Institution	Wuerzburg
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
Hungary	Local Institution	Gyula
Hungary	Local Institution	Veszprem
Italy	Local Institution	Napoli
Italy	Local Institution	Padova
Italy	Local Institution	Reggio Emilia
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Chiba-shi	Chiba
Japan	Local Institution	Higashi-hiroshima-shi	Hiroshima
Japan	Local Institution	Kato-shi	Hyogo
Japan	Local Institution	Kitakyushu-shi	Fukuoka
Japan	Local Institution	Miyazaki-shi	Miyazaki
Japan	Local Institution	Nagano-shi	Nagano
Japan	Local Institution	Nagasaki-shi	Nagasaki
Japan	Local Institution	Osaka-shi	Osaka
Japan	Local Institution	Sasebo-shi	Nagasaki
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Shizuoka-shi	Shizuoka
Japan	Local Institution	Tomigusuku-shi	Okinawa
Japan	Local Institution	Toshima-ku	Tokyo
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Culiacan	Sinaloa
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Morelia	Michioacan
Mexico	Local Institution	San Luis Potosi
Netherlands	Local Institution	Amsterdam
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Poznan
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Russian Federation	Local Institution	Ekaterinburg
Russian Federation	Local Institution	Kazan
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Novosibirsk
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	Yaroslavl
South Africa	Local Institution	Durban	KWA ZULU Natal
South Africa	Local Institution	Panorama	Western CAPE
South Africa	Local Institution	Pinelands, Cape Town	Western Cape
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution	Tygerberg	Western CAPE
Spain	Local Institution	A Coruna
Spain	Local Institution	Madrid
Spain	Local Institution	Santander
Spain	Local Institution	Santiago De Compostela
Spain	Local Institution	Sevilla
Taiwan	Local Institution	Changhua
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taoyuan
United States	East Penn Rheumatology Associates, P.C.	Bethlehem	Pennsylvania
United States	Box Arthritis And Rheumatology Of The Carolinas, Pllc	Charlotte	North Carolina
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Arthritis Associates Of Mississippi	Jackson	Mississippi
United States	Physician Research Collaboration, Llc	Lincoln	Nebraska
United States	Health Research Of Oklahoma	Oklahoma City	Oklahoma
United States	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona
United States	Quincy Medical Group	Quincy	Illinois
United States	Rockford Orthopedic Associates, Llc.	Rockford	Illinois
United States	San Diego Arthritis Medical Clinic	San Diego	California
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	New England Research Associates, Llc	Trumbull	Connecticut
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants Achieving an American College of Rheumatology (ACR) 20% Response Rate	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 12 Weeks
Secondary	Percent of Participants With ACR 20 Response	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 24 weeks
Secondary	Percent of Participants Achieving ACR 50 Response Rate	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 weeks 12 and 24
Secondary	Percent of Participants Achieving ACR 70 Response Rate	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 weeks 12 and 24
Secondary	Mean Change From Baseline in Disease Activity as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)	DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.	Baseline, weeks 12 and 24
Secondary	Percent of Participants With Remission by DAS28-CRP	DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.	At weeks 12 and 24
Secondary	Mean Change From Baseline in Clinical Disease Activity Index (CDAI)	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, weeks 12 and 24
Secondary	Percent of Participants With Remission by CDAI	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	At weeks 12 and 24
Secondary	Mean Change From Baseline in Simplified Disease Activity Index (SDAI)	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, weeks 12 and 24
Secondary	Percent of Participants With Remission by SDAI	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	At weeks 12 and 24
Secondary	Percent of Participants With Remission Rate by Boolean Definition	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 weeks 12 and 24
Secondary	Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Disability Index	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, weeks 12 and 24
Secondary	Mean Change From Baseline in Short Form 36 (SF-36) as Measured by Physical and Mental Components	The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status.	Baseline, weeks 12 and 24
Secondary	Mean Change From Baseline in Fatigue Severity (VAS) Score	A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.	Baseline, weeks 12 and 24
Secondary	Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Scores	The WPAI yeilds four types of scores: Absenteeism (work time missed); Presenteesism (impairment at work / reduced on-the-job effectiveness); Work productivty loss (overall work impairment / absenteeism plus presenteeism); Activity Impairment WPAI outcomes are expressed as impairment percentages with each subscale score ranging from 0-100. The subscale scores are added and averaged to produce a total WPAI score between 0-100. Higher scores indicate greater impairment and less productivity.	Baseline, weeks 12 and 24
Secondary	Mean Change From Baseline in Radiographic (MRI) Progression of Synovitis, Osteitis (Bone Marrow Edema), Bone Erosion and Cartilage Loss (Joint-space Narrowing)		Baseline and week 12
Secondary	Mean Change From Baseline in Radiographic (X-ray) Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijde Total Score	The Sharp-van der Heijde total score ranges from 0-528. Scores for erosion range from 0 to 5 in the hands and 0 to 10 in the feet and reflect erosion size, with 0 defined as no erosion and 3 defined as a large erosion passing the midline of the joint. If there is > 1 erosion per joint, scores can be combined to give a maximum score of 5 per joint in the hands and 10 per joint in the feet (a maximum of 5 at each side of the joint). Joint space narrowing scores vary from 0 to 4 in both the hands and feet, with 0 being normal and 4 being the absence of joint space with evident ankylosis or subluxation. Gross osteolysis and pencil-in-cup change are scored separately and, if present, are assigned the maximum score for erosion and joint space narrowing for the same affected joint. Higher scores indicate increased joint damage.	Baseline and week 24

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