Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA)

NCT01307423 | Completed Phase 3 Results

• 2 other identifiers: CC-10004-PSA-0052010-020324-22
• Study Type: interventional
• Target: 529
• Locations: 18 countries
• Sites: 118

Brief Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis who have not been previously treated with DMARDs. Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.

Conditions

Psoriatic Arthritis

Keywords

psoriasis; Arthritis; Psoriatic Arthritis; inflammation; skin condition; inflammatory cells; apremilast; CC-10004; phosphodiesterase type 4

Outcome Measures

Primary Outcomes (1)

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

  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 assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); -Patient's global assessment of disease activity (measured on a 100 mm VAS); -Physician's global assessment of disease activity (measured on a 100 mm VAS); -Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); -C-Reactive Protein.

  Baseline and Week 16

Secondary Outcomes (52)

• Change From Baseline in Health Assessment Questionnaire- Disability Index [HAQ-DI]) at Week 16

  Baseline and Week 16

• Percentage of Participants With an ACR 20 Response at Week 24

  Baseline and Week 24

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

  Baseline and Week 24

• Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

  Baseline and Week 16

• Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

  Baseline and Week 16

Study Arms (4)

Apremilast 20mg

EXPERIMENTAL

Apremilast 20mg twice daily, orally

Drug: Apremilast 20mg

Apremilast 30mg

EXPERIMENTAL

Apremilast 30mg twice daily, orally

Drug: Apremilast 30mg

Placebo + 20mg Apremilast

PLACEBO COMPARATOR

Placebo + 20mg Apremilast tablets administered twice daily

Drug: Apremilast 20mg; Drug: Placebo

Placebo + 30mg Apremilast

PLACEBO COMPARATOR

Placebo + 30mg Apremilast tablets administered twice daily

Drug: Apremilast 30mg; Drug: Placebo

Interventions

Apremilast 20mg DRUG

Apremilast 20mg twice daily, orally

Also known as: CC-10004

Apremilast 20mg; Placebo + 20mg Apremilast

Apremilast 30mg DRUG

Apremilast 30mg twice daily, orally

Also known as: CC-10004

Apremilast 30mg; Placebo + 30mg Apremilast

Placebo DRUG

Placebo

Placebo + 20mg Apremilast; Placebo + 30mg Apremilast

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Male or female, aged ≥ 18 years 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 (PsA, by any criteria) of ≥ 3 months duration.
• Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening.
• Have ≥ 3 swollen AND ≥ 3 tender joints.
• Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics)
• Be receiving treatment on an outpatient basis.
• If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening.
• If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit.
• Low potency topical corticosteroids (Appendix M or locally available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers' suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit.
• Meet the following laboratory criteria:
• White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and \< 14,000/mm3 (\< 14 x 109/L)
• Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)

You may not qualify if:

• History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.
• Any condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening.
• Pregnant or breast feeding.
• History of allergy to any component of the IP.
• Hepatitis B surface antigen positive at screening.
• Hepatitis C antibody positive at screening.
• AST/SGOT and/or ALT/SGPT \> 1.5 x ULN and total bilirubin \> ULN or albumin \< lower limit of normal (LLN).
• History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
• Active tuberculosis or a history of incompletely treated tuberculosis.
• Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required.
• Active substance abuse or a history of substance abuse within 6 months prior to Screening.
• Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening.
• Malignancy or history of malignancy (except for treated \[ie, cured\] basal cell or squamous cell in situ skin carcinomas and treated \[ie, cured\] cervical intraepithelial neoplasia \[CIN\] or carcinoma in situ of the cervix).
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.

Sponsors & Collaborators

• Amgen: lead

Study Sites (118)

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

In Vivo Clinical Research

Doral, Florida, 33166, United States

Location

Centre For Rheumatology, Immun. And Arthritis

Fort Lauderdale, Florida, 33334, United States

Location

North Florida Dermatology

Jacksonville, Florida, 32204, United States

Location

Florida Center for Dermatology, PA

Saint Augustine, Florida, 32086, United States

Location

Tampa Medical Group Pa

Tampa, Florida, 33614, United States

Location

Atlanta Dermatology, Vein and Research Center, PC

Alpharetta, Georgia, 30022, United States

Location

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, 30342, United States

Location

Sonora Clinical Research, LLC

Boise, Idaho, 83702, United States

Location

Rockford Orthopedic Associates, LLC

Rockford, Illinois, 61107, United States

Location

The Arthritis Center

Springfield, Illinois, 62704, United States

Location

Indiana. University

Indianapolis, Indiana, 46202, United States

Location

Klein and Associates MD, PA

Cumberland, Maryland, 21502, United States

Location

Klein and Associates MD, PA

Hagerstown, Maryland, 21740, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01605, United States

Location

Justus Fiechtner MD PC

Lansing, Michigan, 48910, United States

Location

Heartland Clinical Research, Inc.

Omaha, Nebraska, 68134, United States

Location

Physicians East

Greenville, North Carolina, 27834, United States

Location

Unifour Medical Research Associatets LLC

Hickory, North Carolina, 28602, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Clinical Research Center of Reading, LLP

West Reading, Pennsylvania, 19610, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Austin Regional Clinic

Austin, Texas, 78731, United States

Location

Center for Clinical Studies

Houston, Texas, 77065, United States

Location

Houston Medical Research

Houston, Texas, 77090, United States

Location

Luckster Enterprises

San Antonio, Texas, 78232, United States

Location

Center for Clinical Studies

Webster, Texas, 77598, United States

Location

Rheumatology and Immunotherapy Center

Franklin, Wisconsin, 53132, United States

Location

PharmaSeek

Middleton, Wisconsin, 53562, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Eastern Health Clinical School

Box Hill, 3128, Australia

Location

Repatriation General Hospital

Daws Park, 5041, Australia

Location

Menzies Centre for Population Health Research

Hobart, 7000, Australia

Location

Optimus Clinical Research Pty. Ltd

Kogarah, 2217, Australia

Location

The Queen Elizabeth Hospital

Woodville, 5011, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU de Liege

Liège, 4000, Belgium

Location

Multiprofile Hospital for Active Treatment Trimontsium

Plovdiv, 4000, Bulgaria

Location

17 Diagnostic and Consulting Centre Sofia EOOD

Sofia, 1505, Bulgaria

Location

Multiprofile Hospital for Active Treatment Sv. Ivan Rilski

Sofia, 1606, Bulgaria

Location

Diagnostic-Consultative Center Sveta Anna

Sofia, 1709, Bulgaria

Location

Diagnostic Consulting Center N4

Varna, 9010, Bulgaria

Location

Arthritis Research Centre of Canada

Vancouver, British Columbia, V5Z1L7, Canada

Location

PerCuro Clinical Research

Victoria, British Columbia, V8P5P6, Canada

Location

Manitoba Clinic

Winnipeg, Manitoba, R3A1M3, Canada

Location

St. Clare's Health Care Corporation of St. John's

St. John's, Newfoundland and Labrador, A1C-5B8, Canada

Location

Ultranova Skincare

Barrie, Ontario, L4M 6L2, Canada

Location

William Bensen's Private Practice

Hamilton, Ontario, L8N1Y2, Canada

Location

Rheumatology Research Associates

Ottawa, Ontario, K1H1A2, Canada

Location

Wilderman Medical Clinic

Thornhill, Ontario, L4J1W3, Canada

Location

Probity Medical Research Inc

Waterloo, Ontario, N2J1C4, Canada

Location

Darryl Toth's Private Practice

Windsor, Ontario, N8W 1E6, Canada

Location

Centre de Rhumatologie St-Louis

Sainte-Foy, Quebec, G1W 4R4, Canada

Location

Saskatoon Osteoporosis Centre

Saskatoon, Saskatchewan, S7K 0H6, Canada

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Revmatologicka Ambulance

Prague, 140 00, Czechia

Location

Affidea Praha s.r.o

Prague, 148 00, Czechia

Location

PV - MEDICAL, s.r.o.

Zlín, 760 01, Czechia

Location

East Tallinn Central Hospital

Tallinn, EE-11412, Estonia

Location

North Estonia Regional Hospital

Tallinn, EE-13419, Estonia

Location

Clinical Research Centre Ltd

Tartu, 50106, Estonia

Location

Hotel Dieu

Nantes, 44093, France

Location

Groupe Hospitalier Archet I et II

Nice, 6002, France

Location

Fondation Hôpital Saint-Joseph

Paris, 75014, France

Location

Hopital Lariboisiere

Paris, 75475, France

Location

Qualiclinic kft

Budapest, 1036, Hungary

Location

Synexus Magyarország Kft.

Budapest, 1036, Hungary

Location

Honvéd Kórház - Állami Egészségügyi Központ

Budapest, 1062, Hungary

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Principal SMO Kft.

Makó, 6900, Hungary

Location

MAV Korhaz es Rendelointezet Szolnok

Szolnok, 5000, Hungary

Location

Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Ospedale Luigi Sacco

Milan, 20157, Italy

Location

AOU della II Universita degli Studi di Napoli

Napoli, 80130, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00133, Italy

Location

Ospedale Civile Maggiore Borgo Trento

Verona, 37126, Italy

Location

Siauliai Hospital

Šiauliai, LT-76231, Lithuania

Location

Waikato hospital

Hamilton, 3204, New Zealand

Location

North Shore Hospital

Takapuna, 1309, New Zealand

Location

Timaru Hospital

Timaru, 8601, New Zealand

Location

Bytomskie Centrum Medyczne Silesiana Sp. z o.o.

Bialystok, 15-099, Poland

Location

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Centrum Medyczne Silesiana Sp. z o.o.

Bytom, 41-902, Poland

Location

Synexus SCM Sp. z o.o.

Gdynia, 81-384, Poland

Location

Synexus SCM Sp. z o.o.

Katowice, Poland, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej REUMED

Lublin, 20-582, Poland

Location

Prywatna Praktyka Lekarska

Poznan, 61-397, Poland

Location

REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej

Warsaw, 00-235, Poland

Location

Synexus SCM Sp. z o.o. Oddz. Warszawa

Warsaw, 01-192, Poland

Location

Synexus SCM Sp. z o.o.

Wroclaw, 50-088, Poland

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

C.M.I. Dr. Ciornohuz Adriana

Iași, 700127, Romania

Location

Veterans of Wars Regional Clinical Hospital

Kemerovo, 650000, Russia

Location

Kemerovo State Medical Academy of Roszdrav

Kemerovo, 650066, Russia

Location

Research Medical Complex Vashe Zdorovie

Kezch, 214025, Russia

Location

Krasnoyarsk State Medical Academy

Krasnoyarsk, 660022, Russia

Location

City Clinical Hospital #5

Nizhny Novgorod, 603005, Russia

Location

Research Institute of Clinical Immunology

Novosibirsk, 630099, Russia

Location

Research Institute of Clinical and Experimental Lymphology

Novosibirsk, 630117, 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

Tomsk Regional Clinical Hospital

Tomsk, 634063, Russia

Location

Regional Clinical Hospital

Vladimir, 600023, Russia

Location

Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy

Voronezh, 394066, Russia

Location

Chungnam National University Hospital

Daejeon, 301-721, South Korea

Location

Inha University Hosiptal

Incheon, 400-711, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405-760, South Korea

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

National Taiwan University Hospital

Tapei, 10002, Taiwan

Location

Barnsley Hospital

Barnsley South Yorkshire, S75 2EP, United Kingdom

Location

Haywood Hospital

Burslem, ST6 7AG, United Kingdom

Location

Cannock Chase Hospital

Cannock, WS11 5XY, United Kingdom

Location

Poole Hospital

Poole, BH1 5JB, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (4)

• Mease PJ, Kavanaugh A, Ogdie A, Wells AF, Bergman M, Gladman DD, Richter S, Teng L, Jardon S, Smolen JS. Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naive Patients With Psoriatic Arthritis. J Rheumatol. 2022 Jul;49(7):694-699. doi: 10.3899/jrheum.210906. Epub 2022 Apr 15.

  PMID: 35428720 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

• Wells AF, Edwards CJ, Kivitz AJ, Bird P, Guerette B, Delev N, Paris M, Teng L, Aelion JA. Apremilast monotherapy for long-term treatment of active psoriatic arthritis in DMARD-naive patients. Rheumatology (Oxford). 2022 Mar 2;61(3):1035-1043. doi: 10.1093/rheumatology/keab449.

  PMID: 34100922 DERIVED

• Wells AF, Edwards CJ, Kivitz AJ, Bird P, Nguyen D, Paris M, Teng L, Aelion JA. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology (Oxford). 2018 Jul 1;57(7):1253-1263. doi: 10.1093/rheumatology/key032.

  PMID: 29635379 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic; Psoriasis; Arthritis; Inflammation; Skin Diseases

Interventions

apremilast

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Skin Diseases, Papulosquamous; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

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: November 29, 2010
• First Posted: March 2, 2011
• Study Start: December 9, 2010
• Primary Completion: February 21, 2013
• Study Completion: August 16, 2017
• Last Updated: June 14, 2022
• Results First Posted: August 15, 2014

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

HU (7); BE (2); LI (1); KR (3); CZ (4); TW (2); AU (6); CA (12); BU (5); FR (4); US (30); ES (3); GB (5); RO (4); NZ (3); IT (5); PL (10); RU (12)