Efficacy, Safety, and Tolerability Study of Apremilast to Treat Early Oligoarticular Psoriatic Arthritis. (FOREMOST)

A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Early, Oligoarticular Psoriatic Arthritis Despite Initial Stable Treatment With Either NSAIDS and/or ≤ 1 Conventional Synthetic DMARD

This clinical study will test the effects of a drug called apremilast in oligoarticular psoriatic arthritis with less than 5 years of disease duration. In previous studies, apremilast has been shown to be safe and efficacious in reducing signs and symptoms of psoriatic arthritis, as well as improving physical function. This study will compare the effects of apremilast to placebo on psoriatic arthritis subjects in which the number of affected joints is limited (greater than 1 but less or equal to 4). About 285 patients worldwide will take part in this study.

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic
• Intervention / Treatment: Drug: Apremilast (CC-10004); Other: Apremilast (CC-10004) Placebo

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien Universitaetsklinik fur Innere Medizin I
  • Vienna, Austria, 1130
    • Krankenhaus Hietzing
• Belgium
  • Bruxelles, Belgium, 1070
    • Hôpital Erasme
  • Bruxelles, Belgium, 1020
    • Centre Hospitalier Universitaire Brugmann
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
  • Merksem, Belgium, 2170
    • Ziekenhuis Netwerk Antwerpen Jan Palfijn
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Manitoba Clinic
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Windsor, Ontario, Canada, N8X 1T3
      • Dr Sabeen Anwar Medicine Professional Corporation
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Institut de Rhumatologie de Montreal
• France
  • Orleans cedex 2, France, 45067
    • Centre Hospitalier Regional dOrleans
  • Paris, France, 75010
    • Hopital Lariboisiere
  • Paris, France, 75013
    • Assistance Publique- Hopitaux de Paris AP-HP
  • Toulouse cedex 9, France, 31059
    • CH Toulouse Hopital Pierre-Paul Riquet
• Germany
  • Amberg, Germany, 92224
    • Praxis für Rheumatologie - Amberg
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik gGmbH
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin, Campus Mitte
  • Duesseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Erfurt, Germany, 99096
    • Service Rheuma Erfurt
  • Frankfurt am Main, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt/Main
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Herne, Germany, 44649
    • Rheumazentrum Ruhrgebiet
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
• Italy
  • Bari, Italy, 70124
    • AO Ospedale Policlinico Consorziale Di Bari
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Messina, Italy, 98125
    • Universita degli studi Messina
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Pavia 2, Italy, 27100
    • Policlinico San Matteo Universita Di Pavia
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana
  • Rome, Italy, 00133
    • Fondazione Policlinico Tor Vergata
  • Rozzano MI, Italy, 20089
    • Humanitas Research Hospital Humanitas Mirasole
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo Roma
• Netherlands
  • Enschede, Netherlands, 7512 KZ
    • Medisch Spectrum Twente
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus Medisch Centrum
• Russian Federation
  • Kazan, Russian Federation, 420097
    • Kazan State Medical University
  • Kursk, Russian Federation, 305007
    • Kursk Regional Clinical Hospital
  • Moscow, Russian Federation, 115522
    • Research Institute of Rheumatology named after V A Nasonova
  • Moscow, Russian Federation, 129110
    • Moscow Regional Research Institute n a Vladimirsky
  • Novosibirsk, Russian Federation, 630061
    • Research Institute of Clinical and Experimental Lymphology
  • Petrozavodsk, Russian Federation, 185019
    • Republican Hospital na VA Baranov
  • Rostov-on-don, Russian Federation, 344029
    • Municipal Budgetary Healthcare Institution City Emergency Hospital
  • Saint Petersburg, Russian Federation, 197341
    • Medical Center Sanavita
  • Saint-Petersburg, Russian Federation, 191015
    • Mechnikov North-Western State Medical University
  • Tomsk, Russian Federation, 634063
    • Tomsk Regional Clinical Hospital
• Spain
  • Galdakao, Spain, 48960
    • Hospital Galdakao-Usansolo
  • Gran Canaria, Spain, 35016
    • Hospital Universitario Insular de Gran Canaria
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Merida, Spain, 06800
    • Hospital de Mérida
  • País Vasco
    • Baracaldo, País Vasco, Spain, 48903
      • Hospital Universitario de Cruces
• United Kingdom
  • Derby, United Kingdom, DE1 2QY
    • Royal Berkshire Hospital
  • Eastbourne, United Kingdom, BN21 2UD
    • Eastbourne District General Hospital
  • Edinburgh Scotland, United Kingdom, EH4 2XU
    • Western General Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • Luton, United Kingdom, LU4 0DZ
    • Luton and Dunstable University Hosptial
  • Torquay South Devon, United Kingdom, TQ12 3JX
    • Torbay Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospitals Trust
  • Wolverhampton, United Kingdom, WV10 0QP
    • Wolverhampton Road
• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis and Rheumatology Research, PLLC
  • California
    • Covina, California, United States, 91722
      • Covina Arthritis Clinic
    • Encino, California, United States, 91436
      • Encino Research Center
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • San Diego, California, United States, 92128
      • Rheumatology Center of San Diego PC
    • San Leandro, California, United States, 94578
      • East Bay Rheumatology Medical
    • Thousand Oaks, California, United States, 91360
      • Millennium Clinical Trials
    • Tustin, California, United States, 92780
      • Robin K Dore MD Inc
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials INC
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic PC
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc
    • Fort Lauderdale, Florida, United States, 33309
      • Center for Rheumatology, Immunology, and Arthritis
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology and Immunology Specialists
    • Saint Augustine, Florida, United States, 32080
      • Florida Center for Dermatology
    • Tampa, Florida, United States, 33606-1246
      • Clinical Research of West Florida Inc
    • Tampa, Florida, United States, 33612
      • Carol and Frank Morsani Center for Advanced Health Care
    • Tampa, Florida, United States, 33614
      • BayCare Medical Group Inc
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • North Georgia Rheumatology Group PC
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • RC Rsearch Inc
    • Rockford, Illinois, United States, 61114
      • OrthoIllinois
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves Gilbert Clinic
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management LLC
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Klein and Associates MD, PA - Cumberland
    • Hagerstown, Maryland, United States, 21740
      • Klein and Associates MD PA
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Arthritis and Rheumatology Center of Michigan
    • Lansing, Michigan, United States, 48910
      • Advanced Rheumatology PC
    • Saint Clair Shores, Michigan, United States, 48081
      • Clinical Research Institute of Michigan
  • Minnesota
    • Eagan, Minnesota, United States, 55121
      • Saint Paul Rheumatology PA
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Arthritis, Rheumatic, and Back Disease Associates
  • New York
    • New York, New York, United States, 10003
      • New York University Langone Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Joint and Muscle Research Institute
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research and Consulting LLC
    • Middletown, Ohio, United States, 45044
      • Arthritis and Osteoporosis Center of Southwest Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Philadelphia, Pennsylvania, United States, 19152
      • Arthritis Group
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Piedmont Arthritis Clinic
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute, llc
  • Texas
    • Baytown, Texas, United States, 77521
      • Accurate Clinical Research Incorporated Baytown
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • El Paso, Texas, United States, 79902
      • Texas Arthritis Center PA
    • Lubbock, Texas, United States, 79410
      • West Texas Clinical Research
    • The Woodlands, Texas, United States, 77382
      • Advanced Rheumatology of Houston
    • Webster, Texas, United States, 92103
      • Center For Clinical Studies
  • Washington
    • Seattle, Washington, United States, 98104
      • Seattle Rheumatology Associates
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Rheumatology and Pulmonary Clinic
    • Morgantown, West Virginia, United States, 26505
      • West Virginia Research Institute
    • South Charleston, West Virginia, United States, 25309
      • West Virginia Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 yrs, male or female subject
• Subjects must have signs and symptoms of PsA ≤5 years duration at the time of the Screening Visit
• SJC AND TJC must be >1 and ≤ 4
• For all regions, the local Regulatory Label for treatment with apremilast must be followed.
• Stable doses of protocol-allowed PsA medications
• General good health (except for psoriatic arthritis) as judged by the Investigator, based on medical history, physical examination, and clinical laboratories. (Note: The definition of good health means a subject does not have uncontrolled significant comorbid conditions).
• Comply with protocol-required contraception measures
• Subject meets the Classification Criteria for Psoriatic Arthritis [CASPAR] Criteria for PsA at the Screening visit

Exclusion Criteria:

• Prior use of >2 csDMARD to treat PsA
• Prior exposure to a JAK-inhibitor and/or a biologic DMARD.
• Use of intra-articular (IA) or intra-muscular (IM) glucocorticoid injection within 8 weeks before the Baseline Visit.
• Use of leflunomide within 12 weeks of randomization. Subjects who stopped leflunomide and completed 11 days of treatment with cholestyramine (8 g, 3 x daily) prior to the Baseline Visit may enter the study.
• Prior use of cyclosporine.
• Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
• Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast 30 mg twice daily ± NSAIDs, ≤ 1 csDMARD; Subjects will take ORAL tables of apremilast for up to 48 weeks (30 mg twice daily). Subjects may also receive stable doses of background therapy (standard or care) with NSAIDs, glucorticosteroids and 1 csDMARD as permitted by protocol. After wk. 24, subjects may change the dose /type of permitted Psoriatic Arthritis medications	Drug: Apremilast (CC-10004); Subjects randomized to apremilast will receive dose-titration for the initial 5 days. Apremilast subjects will receive "dummy" titration at wk. 16 (for early escape subjects) and again at week 24 to maintain the blinding of the original treatment assignments. Investigational product (IP) will be dispensed in blinded dose cards until Week 28. Thereafter, IP will be dispensed in open-label bottles.; Other Names: Otezla
Placebo Comparator: Placebo; Subjects will take placebo for up to 24 weeks (twice daily). Subjects may also receive stable doses of background therapy ( standard of care) with NSAIDs, glucocorticosteroids and 1 csDMARD as permitted by protocol. After wk 24, subjects may change the dose /type of permitted PsA medications.	Other: Apremilast (CC-10004) Placebo; Subjects randomized to placebo will receive "dummy" dose-titration for the initial 5 days. Placebo subjects who meet the criteria for early escape at wk. 16 may receive apremilast beginning at wk. 16 and will receive active titration. Remaining placebo subjects will receive active dose titration at week 24. Beginning at wk 24 all subjects will be dispensed active apremilast. Investigational product will be dispensed in blinded dose cards until Week 28. to maintain the blinding of the original treatment assignments. Thereafter, IP will be dispensed in open-label bottles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Clinical State of Minimal Disease Activity (MDA-Joints) Response at Week 16	MDA is defined as tender joint counts (TJC) ≤ 1 and SJC ≤ 1 plus 3 of the following 5 criteria: psoriasis body surface area (BSA) ≤ 3%; patient's pain visual analogue scale (VAS) on a 100 mm scale ≤ 15; where 0 indicates 'no pain' and 100 indicates 'pain as severe as can be imagined'; patient's global assessment of disease activity on a 100 mm scale ≤ 20, where 0 represents the lowest level of disease activity and 100 represents the highest.; physical function assessed by Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5; where 0 represents normal or no difficulty and 3 represents an inability to perform; enthesitis count ≤ 1 based on the Leeds Enthesitis Index; where 0 means nontender and 6 indicates 6 tender tendon insertions.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Remission or Low Disease Activity at Week 16 Based on Clinical Activity in Psoriatic Arthritis (cDAPSA)	The cDAPSA score is based on the numerical summation of 4 disease activity variables: tender and swollen joints, patient's global assessments of disease activity and assessment of pain (VAS). The cDAPSA score ranges from 0 to 154, with a higher score indicating more disease activity. cDAPSA remission is defined as a DAPSA score ≤ 4 and low disease activity is defined as a cDAPSA score > 4 but ≤ 13).	Week 16
Percentage of Participants With SJC ≤ 1 at Week 16	The SJC was based on 66 joints and at week 16 is based on the sentinel joints (i.e., the joints that were affected at baseline). A SJC response is defined as a count ≤ 1.	Week 16
Percentage of Participants With TJC ≤ 1 at Week 16	The TJC was based on 68 joints and at week 16 was based on the sentinel joints (i.e., the joints that were affected at baseline). A TJC response is defined as a count ≤ 1.	Week 16
Percentage of Participants With Patient's Global Assessments of Disease Activity Score of ≤ 20 mm in the VAS at Week 16	The Patient's Global Assessments of Disease Activity is an assessment of how active a participant's psoriatic arthritis was on average during the last week. It was assessed on a VAS ranging from 0 to 100 mm, with a higher score indicating more disease activity. A response is defined as a score ≤ 20 mm.	Week 16
Percentage of Participants With an Assessment of Pain Score ≤ 15 mm in VAS at Week 16	The Patients Pain VAS is the participant's assessment of how much pain they had, on average, during the last week in their joints due to psoriatic arthritis. The VAS score ranges from 0 to 100 mm, with a higher score indicating more pain.	Week 16
Change From Baseline in Psoriatic Arthritis Impact of Disease 12-item for Clinical Trials (PsAID-12) Questionnaire Score at Week 16	The PsAID-12 Questionnaire is a 12-item, self-administered questionnaire that reflects the impact of psoriatic arthritis from the perspective of the participant. The overall score ranges from 0 (best status) to 10 (worst status), with a cut-off ≤ 4 representing patient-acceptable symptom state. Analysis was based on a mixed-effects model for repeated measures (MMRM), which included treatment group, time, treatment group by time interaction, prior/concomitant use of csDMARD (naive, prior use only, both prior and concomitant use) and baseline glucocorticosteroid use (yes/no) per IWRS data as factors, and baseline value as a covariate.	Baseline and Week 16
Percentage of Participants With a Good or Moderate Psoriatic Arthritis Disease Activity (PASDAS) Score at Week 16	The PASDAS is a weighted index comprising assessments of joints, function, acute-phase response, quality of life, and patient and physician VAS. The score range of the PASDAS is 0 - 10, with worse disease activity represented by higher scores. A good response is defined as a PASDAS score of ≤ 3.2 with improvement from baseline ≥ 1.6 points. A moderate response is defined as a PASDAS score > 3.2 with improvement from baseline ≥ 1.6 points; or PASDAS score < 5.4 with improvement from baseline ≥ 0.8 but < 1.6 points.	Baseline and Week 16

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Gossec L, Coates LC, Gladman DD, Aelion JA, Vasandani J, Pinter A, Merola JF, Kavanaugh A, Reddy J, Wang R, Brunori M, Klyachkin Y, Deignan C, Mease PJ. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Sep 16:ard-2024-225833. doi: 10.1136/ard-2024-225833. Online ahead of print.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2018
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: PsA; Apremilast; Standard of care; Oligoarthritis; Oral tablet; Background therapy
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Leprostatic Agents; Thalidomide; Apremilast
• Other Study ID Numbers: CC-10004-PSA-013; U1111-1224-0216 (Registry Identifier: WHO); 2018-002735-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No