Clinical trial NCT01860976: Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis
Official title: A Phase 3 Randomized Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Subcutaneous Injection in Adults With Active Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-05-23
Enrollment: 489
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare subcutaneous Abatacept to placebo in the treatment of psoriatic arthritis

Detailed description: ASTRAEA=Active PSoriaTic ARthritis RAndomizEd TriAl

Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Subjects at least 18 years of age who have a diagnosis of PsA by Classification Criteria for Psoriatic Arthritis (CASPAR)
* Subjects have active PsA as shown by a minimum of ≥3 swollen joints and ≥3 tender joints (66/68 joint counts) at screening and randomization/Day 1 (prior to study drug administration). At least one of the swollen joints must be in the digit of the hand or foot
* Subjects with at least one confirmed ≥2 cm target lesion of plaque psoriasis in a region of the body that can be evaluated excluding the axilla, genitals, groin, palms, and soles
* Subjects must have had an inadequate response or intolerance to at least one non-biologic disease-modifying anti-rheumatic drug (DMARD)
* Subjects may have been exposed to TNFi therapy. Subjects may have discontinued for any reason (inadequate response, intolerance or other)
* Subjects may enroll on certain concomitant non-biologic DMARDs (Methotrexate, Leflunomide, Sulfasalazine, or Hydroxychloroquine) provided the medication has been used for at least 3 months with a stable dose for at least 28 days prior to randomization (Day 1)
* If using oral corticosteroids (≤10 mg mg/day Prednisone equivalent), dose must be stable ≥14 days prior to randomization (Day 1)
* Subjects may enroll on systemic retinoids (eg: Acitretin) provided the medication has been used for at least 3 months with a stable dose for at least 28 days prior to randomization (Day 1)

Exclusion Criteria:

* Subjects with guttate, pustular, or erythrodermic psoriasis
* Subjects who have had prior exposure to Abatacept (CTLA 4Ig) or other CTLA4 therapies
* Subjects who have been exposed to any investigational drug within 4 weeks or 5 half lives, whichever is longer
* Female subjects who had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations
* Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. Subjects with carcinoma in situ, treated with definitive surgical intervention prior to study enrollment are allowed
* Subjects with any bacterial infection within the last 60 days prior to screening (enrollment), unless treated and resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis and bronchiectasis)
* Subjects at risk for tuberculosis (TB). Specifically, subjects with:

  * Current clinical, radiographic or laboratory evidence of active TB
  * A history of active TB within the last 3 years even if it was treated
  * A history of active TB greater than 3 years ago unless there is documentation that the prior anti-TB treatment was appropriate in duration and type
  * Latent TB which was not successfully treated
  * Subjects with a positive TB screening test indicative of latent TB will not be eligible for the study unless they have no evidence of current TB on chest x-ray at screening and they are actively being treated for TB with isoniazid (INH) or other therapy for latent TB given according to local health authority guidelines (eg: Center for Disease Control). Treatment must have been given for at least 4 weeks prior to randomization (Day 1). These subjects should complete treatment according to local health authority guidelines
* Subjects with herpes zoster that resolved less than 2 months prior to enrollment
* Subjects with evidence (as measured by the investigator) of active or latent bacterial, active viral, or serious latent viral infections at the time of enrollment, including subjects with evidence of Immunodeficiency Virus (HIV) infection
* Subjects who are not currently treated with a non-biologic DMARD and have clinical or radiographic evidence of arthritis mutilans (eg: digital telescoping or "pencil-in-cup" radiographic changes)
* Subjects who have failed more than 2 TNFi due to inefficacy defined as inadequate response after 3 months treatment at a therapeutic dose
* Subjects who have received TNFi therapy within 4 weeks for etanercept or within 8 weeks for adalimumab, certolizumab, infliximab, or golimumab
* Subjects who have received prior use of apremilast within 4 weeks, ustekinumab within 20 weeks or briakinumab within 8 weeks
* Subjects who have discontinued a non-biologic DMARD or systemic retinoid within four weeks or five half-lives, whichever is longer, prior to randomization (Day 1)
* Use of any of the following within 28 days or five half lives whichever is longer prior to randomization (Day 1): Cyclosporine A, oral Tacrolimus, Mycophenolate Mofetil (MMF), Hydroxyurea, Fumaric Acid Esters, Paclitaxel, 6-Thioguanine, 6-Mercatopurine, or Tofacitinib

Primary outcomes:
measure: Proportion of ACR 20 Responders at Day 169
timeFrame: Day 169
Secondary outcomes:
measure: Proportion of Health Assessment Questionnaire (HAQ) Responders at Day 169
timeFrame: Baseline to Day 169
measure: Proportion of ACR 20 Responders at Day 169 in the TNFi-naïve Subpopulation
timeFrame: Day 169
measure: Proportion of ACR 20 Responders at Day 169 in the TNFi-exposed Subpopulation
timeFrame: Day 169
measure: Proportion of Non-progressors in Total PsA-modified SHS at Day 169
timeFrame: Baseline to Day 169
measure: Proportion of Participants Achieving a PASI 50 at Day 169 in Participants With Baseline BSA >= 3%
timeFrame: Baseline to Day 169
measure: Proportions of ACR 50 and ACR 70 Responders at Day 169
timeFrame: Day 169
measure: Mean Change From Baseline in SF-36 Physical and Mental Components at Day 169
timeFrame: Baseline to Day 169
measure: Proportion of Participants With at Least One Positive Immunogenicity Response up to Day 169 Relative to Baseline
timeFrame: Baseline to Day 169
measure: Proportion of Participants With AEs at Day 169
timeFrame: Day 169
measure: Proportion of Participants With SAEs at Day 169
timeFrame: Day 169
measure: Proportion of Participants With AEs Leading to Discontinuation at Day 169
timeFrame: Day 169
measure: Proportion of Participant Deaths at Day 169
timeFrame: Day 169
measure: Proportion of Participants With Marked Laboratory Abnormalities at Day 169
timeFrame: Day 169
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research PLLC
state: Arizona
city: Colorado Springs
country: United States
facility: Arthritis Asso & Osteo Ctr Of Colorado Springs
state: Colorado
city: Bridgeport
country: United States
facility: Joao Nascimento
state: Connecticut
city: Trumbull
country: United States
facility: New England Research Associates, Llc
state: Connecticut
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: Hagerstown
country: United States
facility: Klein And Associates, M.D., Pa
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Eagan
country: United States
facility: St. Paul Rheumatology, P.A.
state: Minnesota
city: Charlotte
country: United States
facility: Box Arthritis And Rheumatology Of The Carolinas, Pllc
state: North Carolina
city: Middleburg Heights
country: United States
facility: Paramount Medical Research & Consulting, Llc
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research Of Oklahoma
state: Oklahoma
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, P.C.
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center Of Reading, Llc
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Knoxville
country: United States
facility: Rheumatology Consultants Pllc
state: Tennessee
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest
state: Washington
city: Ciudad Autonoma Beunos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: San Fernando
country: Argentina
facility: Instituto de Asistencia Reumatologica Integral
state: Buenos Aires
city: Rosario
country: Argentina
facility: Caici
state: Santa FE
city: San Miguel De Tucuman
country: Argentina
facility: Centro Medico Privado De Reumatologia
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Instituto De Rehabilitacion Psicofisica
city: Cordoba
country: Argentina
facility: Instituto Reumatologico Strusberg
city: Juiz De Fora
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: St. John's
country: Canada
facility: Nexus Clinical Research
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Toronto Western Hospital, University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Manna Research
state: Ontario
city: Quebec
country: Canada
facility: Groupe De Recherche En Rhumatologie Et Maladies Osseuses
city: Santiago de Chile
country: Chile
facility: Local Institution
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution
state: Valparaiso
city: Santiago de Chile
country: Chile
facility: Local Institution
city: Bogota
country: Colombia
facility: Riesgo De Fractura
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Servimed E.U
city: Cali
country: Colombia
facility: Clinica de Artritis Temprana
city: Praha 11
country: Czechia
facility: Local Institution
city: Praha 2
country: Czechia
facility: Local Institution
city: Praha 4
country: Czechia
facility: Local Institution
city: Chambray Les Tours
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Bad Abbach
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Freiburg
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Ratingen
country: Germany
facility: Local Institution
city: Trier
country: Germany
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Crete
country: Greece
facility: Local Institution
city: Ashkelon
country: Israel
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Ramat-gan
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Firenze
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Palermo
country: Italy
facility: Local Institution
city: Viale Europa Cantanzaro
country: Italy
facility: Local Institution
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Zapopan
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey, N.l.
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Lima
country: Peru
facility: Clinica San Felipe
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Lima
country: Peru
facility: Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac
city: Elblag
country: Poland
facility: Local Institution
state: Warminsko-mazurski
city: Dabrowka
country: Poland
facility: Local Institution
city: Myslowice
country: Poland
facility: Local Institution
city: Warsaw
country: Poland
facility: Local Institution
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution
state: Western CAPE
city: Pinelands, Cape Town
country: South Africa
facility: Local Institution
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Local Institution
state: Western Cape
city: A Coruna
country: Spain
facility: Local Institution
city: Santander
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: McInnes IB, Ferraccioli G, D'Agostino MA, Le Bars M, Banerjee S, Ahmad HA, Elbez Y, Mease PJ. Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a post hoc analysis of a phase III trial. RMD Open. 2019 May 30;5(1):e000934. doi: 10.1136/rmdopen-2019-000934. eCollection 2019.
citation: Strand V, Alemao E, Lehman T, Johnsen A, Banerjee S, Ahmad HA, Mease PJ. Improved patient-reported outcomes in patients with psoriatic arthritis treated with abatacept: results from a phase 3 trial. Arthritis Res Ther. 2018 Dec 6;20(1):269. doi: 10.1186/s13075-018-1769-7.
citation: Mease PJ, Gottlieb AB, van der Heijde D, FitzGerald O, Johnsen A, Nys M, Banerjee S, Gladman DD. Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Ann Rheum Dis. 2017 Sep;76(9):1550-1558. doi: 10.1136/annrheumdis-2016-210724. Epub 2017 May 4.