Safety and Efficacy Study of Apremilast to Treat Psoriatic Arthritis

Last updated: April 28, 2020
Sponsor: Amgen
Overall Status: Completed

Phase

3

Condition

Psoriatic Arthritis

Joint Injuries

Arthritis And Arthritic Pain

Treatment

N/A

Clinical Study ID

NCT01925768
CC-10004-PSA-006
  • Ages > 18
  • All Genders

Study Summary

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

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Males or females, 18 years and older at time of consent.

  2. Must understand and voluntarily sign an informed consent document prior to any studyrelated 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 (by any criteria) of at least 3months' duration

  5. Meet the classification criteria for psoriatic arthritis (CASPAR) at the time ofscreening.

  6. Have at least 3 swollen AND at least 3 tender joints.

  7. Must have high sensitivity C-Reactive Protein (hs-CRP) of at least 0.5 mg/dL atscreening and at baseline.

  8. Must be receiving treatment on an outpatient basis.

  9. Must be tumor necrosis factor (TNF) blocker naive and other Biologic naïve fordermatologic and rheumatic conditions

  10. Subjects taking disease modifying anti-rheumatoid drugs (DMARDs), with the exceptionof cyclosporine and leflunomide (see 7.3. Exclusion Criteria 20, 21), do not require awashout, however, they must discontinue the DMARD treatment at least one day prior totheir baseline visit (ie, Visit 2, Day 0)

  11. Subjects who have been previously treated with leflunomide will require a 12-weekwashout or treatment with the cholestyramine, per leflunomide prescribing label (ie. 8g cholestyramine 3 times daily for 11 days.

  12. Subjects who have been previously treated with cyclosporine will require a 4-weekwashout prior to randomization to participate in the study

  13. If taking oral corticosteroids, must be on a stable dose of prednisone less than orequal to 10 mg/day or equivalent for at least 30 days prior to baseline visit (ie, Day

  1. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, mustbe on stable dose for at least 30 days prior to baseline visit (ie, Day 0) and untilthey have completed the Week 24 study visit.

  2. Must meet the following laboratory criteria:

  • White blood cell count greater than 3000/mm^3 (greater than 3.0 X 10^9/L) andless 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 orequal to twice upper limit of normal (ULN). If initial test shows ALT or ASTgreater than 2 times the ULN, one repeat test is allowed during the screeningperiod.

  • 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, onerepeat 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%

  1. All females of childbearing potential (FCBP) must use one of the approvedcontraceptive options as described below while on investigational product and for atleast 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 ofchildbearing potential's contraceptive measures or ability to become pregnant changes,the investigator will educate the subject regarding contraception options and thecorrect and consistent use of effective contraceptive methods in order to successfullyprevent pregnancy. Females of childbearing potential must have a negative pregnancy test at Screening andBaseline. All FCBP subjects who engage in activity in which conception is possiblemust use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non latex condom NOT made out of natural [animal] membrane [forexample, polyurethane]; PLUS one additional barrier method: (a) diaphragm withspermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge withspermicide.

  2. Male subjects (including those who have had a vasectomy) who engage in activity inwhich conception is possible must use barrier contraception (male latex condom ornonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane])while on investigational product and for at least 28 days after the last dose ofinvestigational product.

Exclusion

Exclusion Criteria:

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

  2. Any condition, including the presence of laboratory abnormalities, which places thesubject at unacceptable risk if he/she were to participate in the study or confoundsthe ability to interpret data from the study.

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

  4. Pregnant or breast feeding.

  5. History of allergy to any component of the investigational product.

  6. Hepatitis B surface antigen positive at screening.

  7. Hepatitis C antibody positive at screening.

  8. History of positive human immunodeficiency virus (HIV), or congenital or acquiredimmunodeficiency (eg, Common Variable Immunodeficiency Disease).

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

  10. Clinically significant abnormality based upon chest radiograph with at leastposterior-anterior (PA) view (the radiograph must be taken within 12 weeks prior toScreening or during the Screening visit). An additional lateral view is stronglyrecommended but not required.

  11. Active substance abuse or a history of substance abuse within 6 months prior toScreening.

  12. Bacterial infections requiring treatment with oral or injectable antibiotics, orsignificant viral or fungal infections, within 4 weeks of Screening. Any treatment forsuch infections must have been completed and the infection cured, at least 4 weeksprior to Screening.

  13. Malignancy or history of malignancy, except for:

  14. treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;

  15. treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situof the cervix with no evidence of recurrence within the previous 5 years.

  16. Major surgery (including joint surgery) within 8 weeks prior to screening or plannedmajor surgery within 6 months following randomization.

  17. Erythrodermic, guttate, or generalized pustular psoriasis at randomization.

  18. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemiclupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma,polymyositis, or fibromyalgia.

  19. Functional Class IV, as defined by the American College of Rheumatology (ACR)Classification of Functional Status in Rheumatoid Arthritis.

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

  21. Prior treatment with more than one non-biologic DMARD

  22. Use of the following systemic therapy(ies) within 4 weeks of randomization:cyclosporine or other calcineurin inhibitors, corticosteroids exceeding 10 mg dailyprednisone equivalent, as well as other oral agents such as retinoids, mycophenolate,thioguanine, hydroxyurea, sirolimus, tacrolimus.

  23. Use of leflunomide within 12 weeks of randomization, unless subject has takencholestyramine, 8g TID (three times a day) x 11 days after stopping leflunomide.

  24. Previous treatment with biologic agents for rheumatic diseases such as, but notlimited to: adalimumab, abatacept, canakinumab, etanercept, golimumab, infliximab,rilonacept, certolizumab pegol, or tocilizumab.

  25. Previous treatment with biologic agents for dermatologic diseases such as alefacept,anti-TNFs (eg etanercept, adalinumab) or ustekinumab.

  26. Previous treatment with tofacitinib, Anti IL-17 agents or secukinumab

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

  28. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column

  29. Any previous treatment with alkylating agents such as cyclophosphamide orchlorambucil, or with total lymphoid irradiation.

  30. Prior treatment with any non-biologic DMARDS other than methotrexate, sulfasalazine,chloroquine, hydroxychloroquine, azathioprine, fumeric acid esters, cyclosporine, orleflunomide

  31. Prior treatment with apremilast, or participation in a clinical study, involvingapremilast

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

Study Design

Total Participants: 219
Study Start date:
September 04, 2013
Estimated Completion Date:
November 17, 2016

Study Description

This is a Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of apremilast monotherapy in subjects with active psoriatic arthritis.

Approximately 214 subjects will be randomized in a 1:1 ratio to either apremilast 30 mg BID (twice a day) or identically-appearing placebo, with approximately 107 subjects per treatment group.

This is a 113-week study. The subjects will spend 24 weeks in the double-blind, placebo-controlled treatment phase, followed by 28 weeks of active treatment phase (ie, up to Week 52 visit). The original treatment assignments (apremilast 30 mg BID (twice a day) or placebo) will remain blinded until all subjects have completed their Week 52 visit (or have discontinued). After the Week 52 visit, all subjects in the extension phase will continue to receive treatment with apremilast 30 mg BID (twice a day) until the end of the study (ie, up to Week 104 visit) or until early discontinuation from the trial.

The study will consist of 5 phases:

  1. Screening Phase - up to 5 weeks

  2. Randomized, Placebo-controlled, Double Blind Treatment Phase - Weeks 0 to 24

  3. Active Treatment Phase - Week 24 to Week 52

  4. Open-label Extension Phase - Week 52 to Week 104

  5. Post-treatment Observational Follow-up Phase

Connect with a study center

  • Westmead Hospital

    Westmead, New South Wales 2145
    Australia

    Site Not Available

  • Menzies Research Institute

    Hobart, Tasmania 7000
    Australia

    Site Not Available

  • Colin Bayliss Research and Teaching Unit

    Victoria Park, Western Australia 6100
    Australia

    Site Not Available

  • Eastern Health Clinical School

    Box Hill, 3128
    Australia

    Site Not Available

  • Royal Prince Alfred Hospital

    Camperdown, 2050
    Australia

    Site Not Available

  • Menzies Centre for Population Health Research

    Hobart,, 7000
    Australia

    Site Not Available

  • Optimus Clinical Research Pty. Ltd

    Kogarah, 2217
    Australia

    Site Not Available

  • Coastal Joint Care

    Maroochydore, 4558
    Australia

    Site Not Available

  • Westmead Cancer Care Center

    Westmead, NSW, 2145
    Australia

    Site Not Available

  • Manna Research

    Vancouver, British Columbia V6J 1S3
    Canada

    Site Not Available

  • Manitoba Clinic

    Winnipeg, Manitoba R3A1M3
    Canada

    Site Not Available

  • Karma Clinical Trials

    Saint John's, Newfoundland and Labrador A1A 4Y3
    Canada

    Site Not Available

  • Nexus Clinical Research

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

    Site Not Available

  • MAC Research Incorporated

    Hamilton, Ontario L8N 2B6
    Canada

    Site Not Available

  • Rheumatology Research Associates

    Ottawa, Ontario K1H 1A2
    Canada

    Site Not Available

  • Arthur Karasik Private Practice

    Toronto, Ontario M9C 5N2
    Canada

    Site Not Available

  • Manna Research

    Toronto, Ontario M9W4L6
    Canada

    Site Not Available

  • Jude Rodrigues Private Practice

    Windsor, Ontario N8X 5A6
    Canada

    Site Not Available

  • Groupe de Recherche en Maladies Osseuses Inc.

    Quebec City, Quebec G1V 3M7
    Canada

    Site Not Available

  • CHUL du CHU de Quebec

    Quebec, G1V 4G2
    Canada

    Site Not Available

  • Revmatologicky Ustav

    Praha, Praha, hlavní mesto 125 8
    Czech Republic

    Site Not Available

  • ARTMEDI UPD s.r.o.

    Hostivice, Praha-západ 253 01
    Czech Republic

    Site Not Available

  • Revmatologicky ustav

    Praha 2, 128 50
    Czechia

    Site Not Available

  • Revmatologicka Ambulance

    Praha 4, 140 00
    Czechia

    Site Not Available

  • Revmatologicka Ambulance

    Sokolov, 356 01
    Czechia

    Site Not Available

  • PV - MEDICAL, s.r.o.

    Zlin, 760 01
    Czechia

    Site Not Available

  • East Tallinn Central Hospital

    Tallinn, EE-11412
    Estonia

    Site Not Available

  • Innomedica Medical and Research Centre

    Tallinn, EE-10117
    Estonia

    Site Not Available

  • Clinical Research Centre Ltd

    Tartu, 50106
    Estonia

    Site Not Available

  • Qualiclinic kft

    Budapest, 1036
    Hungary

    Site Not Available

  • Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

    Debrecen, 4032
    Hungary

    Site Not Available

  • MAV Korhaz es Rendelointezet Szolnok

    Szolnok, 5000
    Hungary

    Site Not Available

  • Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet

    Veszprém, 8200
    Hungary

    Site Not Available

  • Middlemore Hospital

    Otahuhu, Auckland 1640
    New Zealand

    Site Not Available

  • Waikato hospital

    Hamilton, 3204
    New Zealand

    Site Not Available

  • Middlemore Clinical Trials

    Manukau, 1640
    New Zealand

    Site Not Available

  • Timaru Hospital

    Timaru, 8601
    New Zealand

    Site Not Available

  • Covamed SRL

    Sfantu Gheorghe, Covasna 520052
    Romania

    Site Not Available

  • Sf. Maria Clinical Hospital

    Bucharest, 011172
    Romania

    Site Not Available

  • Emergency County Clinical Hospital

    Cluj-Napoca, 400006
    Romania

    Site Not Available

  • Sf Apostol Andrei Emergency Clinical County Hospital

    Galati, 800578
    Romania

    Site Not Available

  • SC Covamed SRL

    Sfantu Gheorghe, Covasna, 520052
    Romania

    Site Not Available

  • Research Medical Complex Vashe Zdorovie

    Kazan, 420103
    Russian Federation

    Site Not Available

  • Nizhniy Novgorod State Medical Academy

    Nizhny Novgorod, 603005
    Russian Federation

    Site Not Available

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

    Penza, 440026
    Russian Federation

    Site Not Available

  • Departmental Hospital at Smolensk Station RZhD JSC

    Smolensk, 214025
    Russian Federation

    Site Not Available

  • Yaroslavl Regional Clinical Hospital

    Yaroslavl, 150062
    Russian Federation

    Site Not Available

  • Clinresco Centre

    Johannesburg, Gauteng 1619
    South Africa

    Site Not Available

  • Jacaranda Hospital

    Pretoria, Gauteng 181
    South Africa

    Site Not Available

  • Panorama Medical Centre

    Cape Town, Western Cape 7500
    South Africa

    Site Not Available

  • Hospital Universitario de Canarias

    La Cuesta, Canarias 38330
    Spain

    Site Not Available

  • Hospital Universitario Vall d'Hebron

    Badalona, Cataluña 08035
    Spain

    Site Not Available

  • Hospital Universitari de Bellvitge

    Hospitalet de Llobregat, Cataluña 08907
    Spain

    Site Not Available

  • Hospital Universitario a Coruna

    A Coruña, 15006
    Spain

    Site Not Available

  • Hospital Vall d'Hebron

    Barcelona, 08035
    Spain

    Site Not Available

  • Hospital Universitari de Bellvitge

    Barcelona, Hospitalet De Llobregat, 08907
    Spain

    Site Not Available

  • Hospital de Basurto-Osakidetza

    Bilbao, 48013
    Spain

    Site Not Available

  • Hospital Universitario de Canarias

    La Laguna, 38320
    Spain

    Site Not Available

  • Hospital Universitario La Paz

    Madrid, 28046
    Spain

    Site Not Available

  • Hospital General de Malaga

    Malaga, 29009
    Spain

    Site Not Available

  • Hospital General Carlos Haya

    Málaga, 29009
    Spain

    Site Not Available

  • Corporacion Sanitaria Parc Tauli

    Sabadell, 08208
    Spain

    Site Not Available

  • Hospital Clinico Universitario de Santiago

    Santiago de Compostela, 15706
    Spain

    Site Not Available

  • Achieve Clinical Research LLC

    Birmingham, Alabama 35216
    United States

    Site Not Available

  • Desert Medical Advances

    Palm Desert, California 92260
    United States

    Site Not Available

  • Bay Area Arthritis and Osteoporosis

    Brandon, Florida 33511
    United States

    Site Not Available

  • Health Point Medical Group

    Brandon, Florida 33511
    United States

    Site Not Available

  • Palmetto Medical Research

    Hialeah, Florida 33016
    United States

    Site Not Available

  • Jeffrey Alper MD Research

    Naples, Florida 34102
    United States

    Site Not Available

  • Suncoast Clinical Research

    New Port Richey, Florida 34652
    United States

    Site Not Available

  • University of South Florida

    Tampa, Florida 33612-4799
    United States

    Site Not Available

  • Coeur D'Alene Arthritis Clinic

    Coeur d'Alene, Idaho 83814
    United States

    Site Not Available

  • Rockford Orthopedic Associates, LLC

    Rockford, Illinois 61107
    United States

    Site Not Available

  • Advanced Rheumatology

    Lansing, Michigan 48910
    United States

    Site Not Available

  • Research West Incorporated

    Kalispell, Montana 59901
    United States

    Site Not Available

  • Heartland Clinical Research, Inc.

    Omaha, Nebraska 68134
    United States

    Site Not Available

  • Physicians East

    Greenville, North Carolina 27834
    United States

    Site Not Available

  • Piedmont Medical Research Associates Inc

    Winston-Salem, North Carolina 27103-3914
    United States

    Site Not Available

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania 16635
    United States

    Site Not Available

  • West Tennessee Research Institute

    Jackson, Tennessee 38305
    United States

    Site Not Available

  • Ramesh C Gupta MD

    Memphis, Tennessee 38119
    United States

    Site Not Available

  • Austin Regional Clinic

    Austin, Texas 78731
    United States

    Site Not Available

  • Baylor Research Institute

    Dallas, Texas 75231
    United States

    Site Not Available

  • Houston Medical Research

    Houston, Texas 77090
    United States

    Site Not Available

  • Arthritis and Osteoporosis Associates LLP

    Lubbock, Texas 79424
    United States

    Site Not Available

  • University of Utah

    Salt Lake City, Utah 84132
    United States

    Site Not Available

  • Tacoma Center for Arthritis Research, PS

    Tacoma, Washington 98405
    United States

    Site Not Available

  • Mountain State Clinical Research

    Clarksburg, West Virginia 26301
    United States

    Site Not Available

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