Psoriatic Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to NSAIDs or Non-biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) Therapy

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging, Multi-Center Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection in Adults With Active Psoriatic Arthritis

The purpose of this study is to characterize the safety, efficacy and dose response of BMS-945429 in subjects with active Psoriatic Arthritis and an inadequate response to Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic Disease modifying anti-rheumatic drugs (DMARDs).

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic
• Intervention / Treatment: Biological: Placebo matching BMS-945429; Biological: BMS-945429; Biological: BMS-945429; Biological: BMS-945429

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Tucuman, Argentina, 4000
    • Local Institution
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1425
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1015
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1428
      • Local Institution
• Australia
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Local Institution
    • Maroochydore, Queensland, Australia, 4558
      • Local Institution
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Local Institution
  • Western Australia
    • Shenton Park, Western Australia, Australia, 6008
      • Local Institution
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Manitoba Clinic
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Local Institution
    • Rimouski, Quebec, Canada, G5L 8W1
      • Centre de Rhumatologie de l Est du Quebec
    • Trois-rivieres, Quebec, Canada, G8Z 1Y2
      • Centre De Recherche Musculo-Squelettique
• Czechia
  • Pardubice, Czechia, 530 02
    • Local Institution
  • Praha 2, Czechia, 128 50
    • Local Institution
• Germany
  • Bad Nauheim, Germany, 61231
    • Local Institution
  • Erlangen, Germany, 91054
    • Local Institution
  • Planegg, Germany, 82152
    • Local Institution
• Hungary
  • Budapest, Hungary, 1023
    • Local Institution
  • Budapest, Hungary, 1062
    • Local Institution
  • Debrecen, Hungary, 4012
    • Local Institution
  • Veszprem, Hungary, 8200
    • Local Institution
• Italy
  • Firenze, Italy, 50139
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution
• Mexico
  • Aguascalientes
    • Mexico, Aguascalientes, Mexico, 20127
      • Local Institution
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45190
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
• Poland
  • Bialystok, Poland, 15-351
    • Local Institution
  • Dabrowka, Poland, 62-069
    • Local Institution
  • Elblag, Poland, 82-300
    • Local Institution
  • Poznan, Poland, 60773
    • Local Institution
  • Warszawa, Poland, 01-868
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Local Institution
  • Yaroslavl, Russian Federation, 150003
    • Local Institution
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0083
      • Local Institution
    • Pretoria, Gauteng, South Africa, 0084
      • Local Institution
  • KWA ZULU Natal
    • Durban, KWA ZULU Natal, South Africa, 4001
      • Local Institution
  • Western CAPE
    • Panorama, Cape Town, Western CAPE, South Africa, 7500
      • Local Institution
  • Western Cape
    • Pinelands, Cape Town, Western Cape, South Africa, 7405
      • Local Institution
• Spain
  • A Coruna, Spain, 15006
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution
  • Sevilla, Spain, 41071
    • Local Institution
• United States
  • California
    • San Diego, California, United States, 92108
      • San Diego Arthritis Medical Clinic
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
  • Connecticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Arthritis Associates Of Mississippi
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Box Arthritis And Rheumatology Of The Carolinas, Pllc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, P.C.

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

Inclusion Criteria:

• Must be on a stable background Methotrexate (MTX) therapy prior to Day1/Randomization. Subjects must have taken MTX for at least 3 months at a dose ≥ 15 mg/week to a maximum weekly dose of ≤ 25 mg/week, and be at a stable dose for 4 weeks prior to randomization (Day 1). Methotrexate dose ≥ 15 mg/week that was not efficacious and that was decreased due to toxicity as low as 10 mg/week is allowed
• Inadequate response to NSAID and/or non-biologic DMARD
• Minimum of 3 swollen and 3 tender joints
• Active psoriatic skin lesions over minimum 3% body surface area
• high sensitivity C-reactive protein (hsCRP) ≥ 0.3 mg/dL

Exclusion Criteria:

• Previously received or currently receiving concomitant biologic therapy

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
Placebo Comparator: PBO: Placebo matching BMS-945429	Biological: Placebo matching BMS-945429; Injection, Subcutaneous, 0 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label
Experimental: BMS-945429 (25mg)	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label
Experimental: BMS-945429 (100mg)	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label
Experimental: BMS-945429 (200mg)	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, every 4 weeks, Short term:24 weeks, Long term: After 24 Wk, selected dose, open-label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Achieving American College of Rheumatology Criteria 20% Response Rate (ACR20)	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 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response Rate	To calculate the PASI score, the psoriasis plaques found on each body region are graded for their combined redness, thickness, and scaliness. The severity of the plaques in each region is graded on a 0 to 4 scale, with 0 meaning no involvement and 4 meaning severe involvement. Next, the amount of surface area on each body region that is covered by the plaques is calculated. The total surface area affected by psoriasis is graded from 0 to 6, with 0 meaning no involvement and 6 meaning greater than 90 percent of the region covered in plaques. These grades are then fed into an equation to determine the patient's PASI score. The PASI score then is used as a clinical assessment of the patient's psoriasis involvement. A person free of psoriasis has a score of 0 and the score could be as high as 72. PASI 75 means that the person's PASI score dropped by 75 percent as a result of the psoriasis treatment.	Week 16 and Week 24
Percent of Participants Achieving ACR50 and ACR70 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).	Week 16 and Week 24
Percent of Participants Achieving ACR20 Response Rate at Week 24	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).	Week 24
Percent of Participants Achieving a Health Assessment Questionnaire (HAQ) Response	For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). There are 20 questions in eight categories of functioning - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The highest component score in each category determines the score for the category, unless aids or devices are required. Dependence on equipment or physical assistance increases a lower score to the level of 2 to more accurately represent underlying disability. The eight category scores are averaged into an overall HAQ score on a scale from zero (no disability) to three (completely disabled). The scale is not truly continuous but has 25 possible values (i.e., 0, 0.125, 0.250, 0.375 … 3). Response is measured by a reduction of at least 0.3 unit from baseline in HAQ index.	Weeks 16 and Week 24
Mean Change From Baseline at Week 16 in Short Form (36) [SF-36] Scores	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 and Week 16
Mean Change From Baseline at Week 24 in SF-36 Scores	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 and Week 24
Number of Participants With Anti-clazakizumab Antibodies		Up to 24 weeks

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

General Publications

• Mease PJ, Gottlieb AB, Berman A, Drescher E, Xing J, Wong R, Banerjee S. The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis. Arthritis Rheumatol. 2016 Sep;68(9):2163-73. doi: 10.1002/art.39700.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 14, 2011
• First Submitted That Met QC Criteria: December 9, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: IM133-004; 2011-004016-29 (EudraCT Number)