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

Arthritis, Psoriatic Clinical Trial

— FOREMOST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03747939
• Other study ID #: CC-10004-PSA-013
• Secondary ID: U1111-1224-02162
• Status: Completed
• Phase: Phase 4
• Start date: December 31, 2018
• Est. completion date: July 5, 2023

Study information

• Verified date: November 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: July 5, 2023
• Est. primary completion date: December 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic

Intervention

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:
• 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

Locations

Country	Name	City	State
Austria	Krankenhaus Hietzing	Vienna
Austria	Universitaetsklinikum Allgemeines Krankenhaus Wien Universitaetsklinik fur Innere Medizin I	Vienna
Belgium	Centre Hospitalier Universitaire Brugmann	Bruxelles
Belgium	Hopital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	Ziekenhuis Netwerk Antwerpen Jan Palfijn	Merksem
Canada	Institut de Rhumatologie de Montreal	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Dr. Sabeen Anwar Medicine Professional Corporation	Windsor	Ontario
Canada	Manitoba Clinic	Winnipeg	Manitoba
France	Centre Hospitalier Regional dOrleans	Orleans cedex 2
France	Assistance Publique- Hopitaux de Paris AP-HP	Paris
France	Hopital Lariboisiere	Paris
France	CH Toulouse Hopital Pierre-Paul Riquet	Toulouse cedex 9
Germany	Praxis fur Rheumatologie - Amberg	Amberg
Germany	Kerckhoff-Klinik gGmbH	Bad Nauheim
Germany	Charité Campus Mitte	Berlin
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Service Rheuma Erfurt	Erfurt
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt/Main	Frankfurt am Main
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Italy	AO Ospedale Policlinico Consorziale Di Bari	Bari
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Italy	Universita degli studi Messina	Messina
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Policlinico San Matteo Universita Di Pavia	Pavia 2
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Tor Vergata	Rome
Italy	Humanitas Research Hospital Humanitas Mirasole	Rozzano MI
Italy	Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo Roma	Verona
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Erasmus Medisch Centrum	Rotterdam
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	Kursk Regional Clinical Hospital	Kursk
Russian Federation	Moscow Regional Research Institute n.a. Vladimirsky	Moscow
Russian Federation	Research Institute of Rheumatology named after V.A.Nasonova	Moscow
Russian Federation	Research Institute of Clinical and Experimental Lymphology	Novosibirsk
Russian Federation	Republican Hospital na VA Baranov	Petrozavodsk
Russian Federation	Municipal Budgetary Healthcare Institution City Emergency Hospital	Rostov-on-don
Russian Federation	Medical Center Sanavita	Saint Petersburg
Russian Federation	Mechnikov North-Western State Medical University	Saint-Petersburg
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Spain	Hospital Universitario de Cruces	Baracaldo	País Vasco
Spain	Hospital Galdakao-Usansolo	Galdakao
Spain	Hospital Universitario Insular de Gran Canaria	Gran Canaria
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital de Merida	Merida
United Kingdom	Royal Berkshire Hospital	Derby
United Kingdom	Eastbourne District General Hospital	Eastbourne
United Kingdom	Western General Hospital	Edinburgh Scotland
United Kingdom	Kings College Hospital	London
United Kingdom	Luton and Dunstable University Hosptial	Luton
United Kingdom	Torbay Hospital	Torquay South Devon
United Kingdom	Royal Cornwall Hospitals Trust	Truro
United Kingdom	Wolverhampton Road	Wolverhampton
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Accurate Clinical Research Incorporated Baytown	Baytown	Texas
United States	Rheumatology and Pulmonary Clinic	Beckley	West Virginia
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	Joint and Muscle Research Institute	Charlotte	North Carolina
United States	Clinical Research of West Florida, Inc	Clearwater	Florida
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	Covina Arthritis Clinic	Covina	California
United States	Klein and Associates MD, PA - Cumberland	Cumberland	Maryland
United States	Denver Arthritis Clinic PC	Denver	Colorado
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Saint Paul Rheumatology PA	Eagan	Minnesota
United States	Texas Arthritis Center PA	El Paso	Texas
United States	Encino Research Center	Encino	California
United States	Center for Rheumatology, Immunology, and Arthritis	Fort Lauderdale	Florida
United States	Providence Medical Foundation	Fullerton	California
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Piedmont Arthritis Clinic	Greenville	South Carolina
United States	Klein and Associates MD PA	Hagerstown	Maryland
United States	RC Rsearch Inc	Hinsdale	Illinois
United States	West Tennessee Research Institute, LLC	Jackson	Tennessee
United States	Advanced Rheumatology PC	Lansing	Michigan
United States	Arthritis and Rheumatology Center of Michigan	Lansing	Michigan
United States	North Georgia Rheumatology Group PC	Lawrenceville	Georgia
United States	West Texas Clinical Research	Lubbock	Texas
United States	Arizona Arthritis and Rheumatology Research, PLLC	Mesa	Arizona
United States	Clinical Trials Management LLC	Metairie	Louisiana
United States	Paramount Medical Research and Consulting LLC	Middleburg Heights	Ohio
United States	Arthritis and Osteoporosis Center of Southwest Ohio	Middletown	Ohio
United States	West Virginia Research Institute	Morgantown	West Virginia
United States	New York University Langone Medical Center	New York	New York
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Arthritis Group	Philadelphia	Pennsylvania
United States	Integral Rheumatology and Immunology Specialists	Plantation	Florida
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	OrthoIllinois	Rockford	Illinois
United States	Florida Center For Dermatology	Saint Augustine	Florida
United States	Clinical Research Institute of Michigan	Saint Clair Shores	Michigan
United States	Rheumatology Center of San Diego PC	San Diego	California
United States	East Bay Rheumatology Medical	San Leandro	California
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	West Virginia Research Institute	South Charleston	West Virginia
United States	Baycare Medical Group Inc	Tampa	Florida
United States	Carol and Frank Morsani Center for Advanced Health Care	Tampa	Florida
United States	Clinical Research of West Florida Inc	Tampa	Florida
United States	Advanced Rheumatology of Houston	The Woodlands	Texas
United States	Millennium Clinical Trials	Thousand Oaks	California
United States	Robin K Dore MD Inc	Tustin	California
United States	Inland Rheumatology Clinical Trials Inc	Upland	California
United States	Arthritis, Rheumatic, and Back Disease Associates	Voorhees	New Jersey
United States	Center for Clinical Studies	Webster	Texas
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   AmgenTrials clinical trials website