Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis

NCT01925768 | Completed Phase 3 Results DMC

• 1 other identifier: CC-10004-PSA-006
• Study Type: interventional
• Target: 219
• Locations: 9 countries
• Sites: 68

Brief Summary

The purpose of this study is to determine whether apremilast is safe and effective for treating patients with psoriatic arthritis.

Conditions

Psoriatic Arthritis

Keywords

Apremilast, Psoriatic Arthritis, PDE4 inhibitor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) Response at Week 16

  Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 78 tender joint count; * ≥ 20% improvement in 76 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: * Patient's self-assessment of pain (measured on a 0 to 10 unit numeric rating scale \[NRS\]); * Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS); * Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS); * Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); * C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders.

  Baseline and Week 16

Secondary Outcomes (21)

• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24

  Baseline and Week 24

• Percentage of Participants Who Achieved an American College of Rheumatology 20% (ACR20) at Week 24

  Baseline and Week 24

• Change From Baseline in the 28-Joint Disease Activity Score Using C-reactive Protein as the Acute-Phase Reactant (DAS28 [CRP]) at Week 24

  Baseline and Week 24

• Change From Baseline in the Medical Outcomes Short Form Health Survey (SF-36) V2 Physical Function Domain Score at Week 24

  Baseline and Week 24

• Change From Baseline in the 36-item SF-36 Physical Component Summary Score at Week 24

  Baseline and Week 24

Study Arms (2)

Apremilast 30 mg

EXPERIMENTAL

30 mg Apremilast tablets administered twice daily (BID) for 24 weeks during the double-blind placebo-controlled phase; followed by 30 mg Apremilast BID for 28 weeks of active treatment phase (up to the 52 week visit); original treatment assignments remain blinded until all participants have completed their 52 week visit or have discontinued. After the Wk 52 visit, all participants in the extension phase will continue to receive treatment with apremilast 30 mg BID until the end of the study (ie, up to Week 104 visit) or until early discontinuation from the trial.

Drug: Apremilast 30 mg

Placebo

PLACEBO COMPARATOR

Oral placebo BID during the placebo controlled phase weeks 0 to 24; placebo treated participants whose improvement is \<10% in both swollen and tender joint counts at Week 16 are eligible for early escape (based on the measure of clinical benefit from their current treatment as evidenced by improvement (or lack of improvement) in 1) the physician (evaluator's) global assessment (EGA), 2) patients pain (pain NRS), 3) the patient global assessments (PGA), and 4) the health assessment questionnaire disability index (HAQ-DI); Placebo-treated patients who early escape are transitioned to apremilast 30 mg PO BID during the active treatment phase up to their Week 52 visit; all those who complete the 52-week treatment phase will enter an open-label extension phase for an additional 52 weeks or until early discontinuation from the trial.

Drug: Placebo

Interventions

Apremilast 30 mg DRUG

30mg of Apremilast will be orally administered twice daily for 104 weeks

Also known as: Otezla, CC-10004

Apremilast 30 mg

Placebo DRUG

Identically appearing Placebo tablets will be orally administered twice daily for up to 24 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, 18 years and older at time of consent.
• Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Have a documented diagnosis of psoriatic arthritis (by any criteria) of at least 3 months' duration
• Meet the classification criteria for psoriatic arthritis (CASPAR) at the time of screening.
• Have at least 3 swollen AND at least 3 tender joints.
• Must have high sensitivity C-Reactive Protein (hs-CRP) of at least 0.5 mg/dL at screening and at baseline.
• Must be receiving treatment on an outpatient basis.
• Must be tumor necrosis factor (TNF) blocker naive and other Biologic naïve for dermatologic and rheumatic conditions

You may not qualify if:

• Subjects who have been previously treated with leflunomide will require a 12-week washout or treatment with the cholestyramine, per leflunomide prescribing label (ie. 8 g cholestyramine 3 times daily for 11 days.
• Subjects who have been previously treated with cyclosporine will require a 4-week washout prior to randomization to participate in the study
• If taking oral corticosteroids, must be on a stable dose of prednisone less than or equal to 10 mg/day or equivalent for at least 30 days prior to baseline visit (ie, Day 0)
• If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 30 days prior to baseline visit (ie, Day 0) and until they have completed the Week 24 study visit.
• Must meet the following laboratory criteria:
• White blood cell count greater than 3000/mm\^3 (greater than 3.0 X 10\^9/L) and less than 14,000/mm\^3 (less than 14 X 10\^9/L)
• Platelet count at least 100,000/mm\^3 (at least 100 X 10\^9/L)
• Serum creatinine less than or equal to 1.5 mg/dL (less than or equal to 132.6 μmol/L)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to twice upper limit of normal (ULN). If initial test shows ALT or AST greater than 2 times the ULN, one repeat test is allowed during the screening period.
• Total bilirubin less than or equal to 2 mg/dL (less than or equal to 34 μmol/L) or Albumin greater than LLN. If initial test result is greater than 2 mg/dL, one repeat test is allowed during the screening period.
• Hemoglobin at least 9 g/dL (at least 5.6 mmol/L)
• Hemoglobin A1c less than or equal to 9.0%
• All females of childbearing potential (FCBP) must use one of the approved contraceptive options as described below while on investigational product and for at least 28 days after administration of the last dose of the investigational product.
• At the time of study entry, and at any time during the study when a female subject of childbearing potential's contraceptive measures or ability to become pregnant changes, the investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy.
• Females of childbearing potential must have a negative pregnancy test at Screening and Baseline. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

Sponsors & Collaborators

• Amgen: lead

Study Sites (71)

Achieve Clinical Research LLC

Birmingham, Alabama, 35216, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Bay Area Arthritis and Osteoporosis

Brandon, Florida, 33511, United States

Location

Health Point Medical Group

Brandon, Florida, 33511, United States

Location

Palmetto Medical Research

Hialeah, Florida, 33016, United States

Location

Jeffrey Alper MD Research

Naples, Florida, 34102, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

University of South Florida

Tampa, Florida, 33612-4799, United States

Location

Coeur D'Alene Arthritis Clinic

Coeur d'Alene, Idaho, 83814, United States

Location

Rockford Orthopedic Associates, LLC

Rockford, Illinois, 61107, United States

Location

Advanced Rheumatology

Lansing, Michigan, 48910, United States

Location

Research West Incorporated

Kalispell, Montana, 59901, United States

Location

Heartland Clinical Research, Inc.

Omaha, Nebraska, 68134, United States

Location

Physicians East

Greenville, North Carolina, 27834, United States

Location

Piedmont Medical Research Associates Inc

Winston-Salem, North Carolina, 27103-3914, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Ramesh C Gupta MD

Memphis, Tennessee, 38119, United States

Location

Austin Regional Clinic

Austin, Texas, 78731, United States

Location

Baylor Research Institute

Dallas, Texas, 75231, United States

Location

Houston Medical Research

Houston, Texas, 77090, United States

Location

Arthritis and Osteoporosis Associates LLP

Lubbock, Texas, 79424, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Mountain State Clinical Research

Clarksburg, West Virginia, 26301, United States

Location

Colin Bayliss Research and Teaching Unit

Victoria Park, Western Australia, 6100, Australia

Location

Eastern Health Clinical School

Box Hill, 3128, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Menzies Centre for Population Health Research

Hobart, 7000, Australia

Location

Optimus Clinical Research Pty. Ltd

Kogarah, 2217, Australia

Location

Coastal Joint Care

Maroochydore, 4558, Australia

Location

Westmead Cancer Care Center

Westmead, NSW, 2145, Australia

Location

Manna Research

Vancouver, British Columbia, V6J 1S3, Canada

Location

Manitoba Clinic

Winnipeg, Manitoba, R3A1M3, Canada

Location

Karma Clinical Trials

St. John's, Newfoundland and Labrador, A1A 4Y3, Canada

Location

Nexus Clinical Research

St. John's, Newfoundland and Labrador, A1A 5E8, Canada

Location

MAC Research Incorporated

Hamilton, Ontario, L8N 2B6, Canada

Location

Arthur Karasik Private Practice

Toronto, Ontario, M9C 5N2, Canada

Location

Manna Research

Toronto, Ontario, M9W4L6, Canada

Location

Jude Rodrigues Private Practice

Windsor, Ontario, N8X 5A6, Canada

Location

CHUL du CHU de Quebec

Québec, G1V 4G2, Canada

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Revmatologicka Ambulance

Prague, 140 00, Czechia

Location

Revmatologicka Ambulance

Sokolov, 356 01, Czechia

Location

PV - MEDICAL, s.r.o.

Zlín, 760 01, Czechia

Location

Innomedica Medical and Research Centre

Tallinn, EE-10117, Estonia

Location

East Tallinn Central Hospital

Tallinn, EE-11412, Estonia

Location

Clinical Research Centre Ltd

Tartu, 50106, Estonia

Location

Qualiclinic kft

Budapest, 1036, Hungary

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

MAV Korhaz es Rendelointezet Szolnok

Szolnok, 5000, Hungary

Location

Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet

Veszprém, 8200, Hungary

Location

Waikato hospital

Hamilton, 3204, New Zealand

Location

Middlemore Clinical Trials

Manukau, 1640, New Zealand

Location

Timaru Hospital

Timaru, 8601, New Zealand

Location

Sf. Maria Clinical Hospital

Bucharest, 011172, Romania

Location

Emergency County Clinical Hospital

Cluj-Napoca, 400006, Romania

Location

Sf Apostol Andrei Emergency Clinical County Hospital

Galati, 800578, Romania

Location

SC Covamed SRL

Sfantu Gheorghe, Covasna, 520052, Romania

Location

Research Medical Complex Vashe Zdorovie

Kazan', 420103, Russia

Location

Penza Regional Clinical Hospital n.a. N.N. Burdenko

Penza, 440026, Russia

Location

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, 214025, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, 150062, Russia

Location

Hospital Universitario a Coruna

A Coruña, 15006, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Hospitalet de Llobregat, 08907, Spain

Location

Hospital de Basurto-Osakidetza

Bilbao, 48013, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General Carlos Haya

Málaga, 29009, Spain

Location

Corporacion Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Related Publications (2)

• Nash P, Ohson K, Walsh J, Delev N, Nguyen D, Teng L, Gomez-Reino JJ, Aelion JA; ACTIVE investigators. Early and sustained efficacy with apremilast monotherapy in biological-naive patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE). Ann Rheum Dis. 2018 May;77(5):690-698. doi: 10.1136/annrheumdis-2017-211568. Epub 2018 Jan 17.

  PMID: 29343507 BACKGROUND

• Mease PJ, Hatemi G, Paris M, Cheng S, Maes P, Zhang W, Shi R, Flower A, Picard H, Stein Gold L. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behcet's Syndrome. Am J Clin Dermatol. 2023 Sep;24(5):809-820. doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.

  PMID: 37316690 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

apremilast

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Anne McClain, Senior Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2013
• First Posted: August 20, 2013
• Study Start: September 4, 2013
• Primary Completion: February 25, 2015
• Study Completion: November 17, 2016
• Last Updated: May 12, 2020
• Results First Posted: June 13, 2016

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

RU (4); US (24); CZ (4); CA (9); HU (4); RO (4); ES (9); AU (7); NZ (3)