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

NCT ID: NCT01307423

Last Updated: 2022-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 529 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-09
• Study Completion Date: 2017-08-16

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.

Detailed Description

Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.

Conditions

Psoriatic Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Apremilast 20mg

Apremilast 20mg twice daily, orally

Group Type: EXPERIMENTAL

Apremilast 20mg

Intervention Type: DRUG

Apremilast 20mg twice daily, orally

Apremilast 30mg

Apremilast 30mg twice daily, orally

Group Type: EXPERIMENTAL

Apremilast 30mg

Intervention Type: DRUG

Apremilast 30mg twice daily, orally

Placebo + 20mg Apremilast

Placebo + 20mg Apremilast tablets administered twice daily

Group Type: PLACEBO_COMPARATOR

Apremilast 20mg

Intervention Type: DRUG

Apremilast 20mg twice daily, orally

Placebo

Intervention Type: DRUG

Placebo

Placebo + 30mg Apremilast

Placebo + 30mg Apremilast tablets administered twice daily

Group Type: PLACEBO_COMPARATOR

Apremilast 30mg

Intervention Type: DRUG

Apremilast 30mg twice daily, orally

Placebo

Intervention Type: DRUG

Placebo

Interventions

Apremilast 20mg

Apremilast 20mg twice daily, orally

Intervention Type: DRUG

Apremilast 30mg

Apremilast 30mg twice daily, orally

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

CC-10004; CC-10004

Eligibility Criteria

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

1. Male or female, aged ≥ 18 years at time of consent.

2. Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Have a documented diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 3 months duration.

5. Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at time of screening.

6. Have ≥ 3 swollen AND ≥ 3 tender joints.

7. Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS) (small molecules or biologics)

8. Be receiving treatment on an outpatient basis.

9. 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.

10. 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.

11. 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.

12. 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)
• Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L)
• Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x upper limit of normal (ULN)
• Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L)
• Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
• Hemoglobin A1c ≤ 9.0%

13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on IP and for at least 28 days after the last dose of IP.

14. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on investigational product (IP) and for at least 28 days after the last dose of IP: one highly effective form (ie, hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane) with either of the following: sponge with spermicide or diaphragm with spermicide.

18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis.

19. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q).

20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease).

21. Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or biologics).

23. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA).

24. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).

25. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within 6 months of baseline.

26. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.

27. Prior treatment with apremilast.

28. Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/ pharmacodynamic half lives, if known (whichever is longer).

Exclusion Criteria

1. History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.

2. 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.

3. Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening.

4. Pregnant or breast feeding.

5. History of allergy to any component of the IP.

6. Hepatitis B surface antigen positive at screening.

7. Hepatitis C antibody positive at screening.

8. AST/SGOT and/or ALT/SGPT > 1.5 x ULN and total bilirubin > ULN or albumin < lower limit of normal (LLN).

9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).

10. Active tuberculosis or a history of incompletely treated tuberculosis.

11. 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.

12. Active substance abuse or a history of substance abuse within 6 months prior to Screening.

13. 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.

14. 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).

15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.

16. Erythrodermic, guttate, or pustular psoriasis.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Arizona Research Center

Phoenix, Arizona, United States

Desert Medical Advances

Palm Desert, California, United States

In Vivo Clinical Research

Doral, Florida, United States

Centre For Rheumatology, Immun. And Arthritis

Fort Lauderdale, Florida, United States

North Florida Dermatology

Jacksonville, Florida, United States

Florida Center for Dermatology, PA

Saint Augustine, Florida, United States

Tampa Medical Group Pa

Tampa, Florida, United States

Atlanta Dermatology, Vein and Research Center, PC

Alpharetta, Georgia, United States

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, United States

Sonora Clinical Research, LLC

Boise, Idaho, United States

Rockford Orthopedic Associates, LLC

Rockford, Illinois, United States

The Arthritis Center

Springfield, Illinois, United States

Indiana. University

Indianapolis, Indiana, United States

Klein and Associates MD, PA

Cumberland, Maryland, United States

Klein and Associates MD, PA

Hagerstown, Maryland, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Justus Fiechtner MD PC

Lansing, Michigan, United States

Heartland Clinical Research, Inc.

Omaha, Nebraska, United States

Physicians East

Greenville, North Carolina, United States

Unifour Medical Research Associatets LLC

Hickory, North Carolina, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Clinical Research Center of Reading, LLP

West Reading, Pennsylvania, United States

West Tennessee Research Institute

Jackson, Tennessee, United States

Austin Regional Clinic

Austin, Texas, United States

Center for Clinical Studies

Houston, Texas, United States

Houston Medical Research

Houston, Texas, United States

Luckster Enterprises

San Antonio, Texas, United States

Center for Clinical Studies

Webster, Texas, United States

Rheumatology and Immunotherapy Center

Franklin, Wisconsin, United States

PharmaSeek

Middleton, Wisconsin, United States

Monash Medical Centre

Clayton, Victoria, Australia

Eastern Health Clinical School

Box Hill, , Australia

Repatriation General Hospital

Daws Park, , Australia

Menzies Centre for Population Health Research

Hobart, , Australia

Optimus Clinical Research Pty. Ltd

Kogarah, , Australia

The Queen Elizabeth Hospital

Woodville, , Australia

UZ Leuven

Leuven, , Belgium

CHU de Liege

Liège, , Belgium

Multiprofile Hospital for Active Treatment Trimontsium

Plovdiv, , Bulgaria

17 Diagnostic and Consulting Centre Sofia EOOD

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment Sv. Ivan Rilski

Sofia, , Bulgaria

Diagnostic-Consultative Center Sveta Anna

Sofia, , Bulgaria

Diagnostic Consulting Center N4

Varna, , Bulgaria

Arthritis Research Centre of Canada

Vancouver, British Columbia, Canada

PerCuro Clinical Research

Victoria, British Columbia, Canada

Manitoba Clinic

Winnipeg, Manitoba, Canada

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

St. John's, Newfoundland and Labrador, Canada

Ultranova Skincare

Barrie, Ontario, Canada

William Bensen's Private Practice

Hamilton, Ontario, Canada

Rheumatology Research Associates

Ottawa, Ontario, Canada

Wilderman Medical Clinic

Thornhill, Ontario, Canada

Probity Medical Research Inc

Waterloo, Ontario, Canada

Darryl Toth's Private Practice

Windsor, Ontario, Canada

Centre de Rhumatologie St-Louis

Sainte-Foy, Quebec, Canada

Saskatoon Osteoporosis Centre

Saskatoon, Saskatchewan, Canada

Revmatologicky ustav

Prague, , Czechia

Revmatologicka Ambulance

Prague, , Czechia

Affidea Praha s.r.o

Prague, , Czechia

PV - MEDICAL, s.r.o.

Zlín, , Czechia

East Tallinn Central Hospital

Tallinn, , Estonia

North Estonia Regional Hospital

Tallinn, , Estonia

Clinical Research Centre Ltd

Tartu, , Estonia

Hotel Dieu

Nantes, , France

Groupe Hospitalier Archet I et II

Nice, , France

Fondation Hôpital Saint-Joseph

Paris, , France

Hopital Lariboisiere

Paris, , France

Qualiclinic kft

Budapest, , Hungary

Synexus Magyarország Kft.

Budapest, , Hungary

Honvéd Kórház - Állami Egészségügyi Központ

Budapest, , Hungary

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, , Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Principal SMO Kft.

Makó, , Hungary

MAV Korhaz es Rendelointezet Szolnok

Szolnok, , Hungary

Azienda Ospedaliera Universitaria San Martino

Genova, , Italy

Ospedale Luigi Sacco

Milan, , Italy

AOU della II Universita degli Studi di Napoli

Napoli, , Italy

Fondazione PTV Policlinico Tor Vergata

Roma, , Italy

Ospedale Civile Maggiore Borgo Trento

Verona, , Italy

Siauliai Hospital

Šiauliai, , Lithuania

Waikato hospital

Hamilton, , New Zealand

North Shore Hospital

Takapuna, , New Zealand

Timaru Hospital

Timaru, , New Zealand

Bytomskie Centrum Medyczne Silesiana Sp. z o.o.

Bialystok, , Poland

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Centrum Medyczne Silesiana Sp. z o.o.

Bytom, , Poland

Synexus SCM Sp. z o.o.

Gdynia, , Poland

Synexus SCM Sp. z o.o.

Katowice, , Poland

Niepubliczny Zaklad Opieki Zdrowotnej REUMED

Lublin, , Poland

Prywatna Praktyka Lekarska

Poznan, , Poland

REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej

Warsaw, , Poland

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

Warsaw, , Poland

Synexus SCM Sp. z o.o.

Wroclaw, , Poland

Sf. Maria Clinical Hospital

Bucharest, , Romania

Emergency County Clinical Hospital

Cluj-Napoca, , Romania

Sf Apostol Andrei Emergency Clinical County Hospital

Galati, , Romania

C.M.I. Dr. Ciornohuz Adriana

Iași, , Romania

Veterans of Wars Regional Clinical Hospital

Kemerovo, , Russia

Kemerovo State Medical Academy of Roszdrav

Kemerovo, , Russia

Research Medical Complex Vashe Zdorovie

Kezch, , Russia

Krasnoyarsk State Medical Academy

Krasnoyarsk, , Russia

City Clinical Hospital #5

Nizhny Novgorod, , Russia

Research Institute of Clinical Immunology

Novosibirsk, , Russia

Research Institute of Clinical and Experimental Lymphology

Novosibirsk, , Russia

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

Penza, , Russia

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, , Russia

Tomsk Regional Clinical Hospital

Tomsk, , Russia

Regional Clinical Hospital

Vladimir, , Russia

Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy

Voronezh, , Russia

Chungnam National University Hospital

Daejeon, , South Korea

Inha University Hosiptal

Incheon, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Taipei Veterans General Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Tapei, , Taiwan

Barnsley Hospital

Barnsley South Yorkshire, , United Kingdom

Haywood Hospital

Burslem, , United Kingdom

Cannock Chase Hospital

Cannock, , United Kingdom

Poole Hospital

Poole, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; Australia; Belgium; Bulgaria; Canada; Czechia; Estonia; France; Hungary; Italy; Lithuania; New Zealand; Poland; Romania; Russia; South Korea; Taiwan; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 35428720 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37316690 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34100922 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29635379 (View on PubMed)

Other Identifiers

2010-020324-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-10004-PSA-005

Identifier Type: -

Identifier Source: org_study_id