MOSAIC: A Study to Evaluate the Impact of Apremilast (CC-10004) on MRI Outcomes in Subjects With Psoriatic Arthritis
Study Details
Study Description
Brief Summary
This is a Phase 4, multicenter, single-arm, open-label study to evaluate the impact of apremilast, either in monotherapy or with stable Methotrexate (MTX), on Magnetic resonance imaging (MRI) outcomes in subjects with active PsA with up to 5 years of disease duration (since diagnosis).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Approximately 120 subjects will receive apremilast 30 mg BID, after a 5-day titration period, with or without MTX. All subjects will be permitted to take NSAIDs and/or low-dose oral glucocorticoids (prednisone ≤ 10 mg/day or equivalent) throughout the study. The NSAIDs and low-dose oral glucocorticoids must be on a stable regimen for at least 4 weeks prior to baseline. MTX (≤ 25 mg/week) will be permitted if treatment duration is ≥ 6 months and on a stable regimen for at least 3 months prior to baseline. In addition, Nonsteroidal anti-inflammatory drug (NSAIDs), and low-dose glucocorticoids must be continued from Day 1 through the Week 24 Visit. Change in doses, increase or decrease, and/or discontinuation will not be allowed, except for safety reasons or for lack of availability. After the Week 24 Visit, the doses of MTX, NSAIDs, or glucocorticoids may be adjusted as clinically required.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Administration of CC-10004 Apremilast 30 mg BID in monotherapy or in combination with Methotrexate |
Drug: CC-10004
CC-10004
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in the composite score of BME, synovitis, and tenosynovitis assessed by Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) [24 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
Secondary Outcome Measures
- Change from baseline in the composite score of BME, synovitis, and tenosynovitis assessed by PsAMRIS [48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in the composite score of BME and synovitis assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in the PsAMRIS total inflammation score [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in BME assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in synovitis assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in tenosynovitis assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in periarticular inflammation assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in the PsAMRIS total damage score [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in bone erosion assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Change from baseline in bone proliferation/enthesophytes assessed by PsAMRIS [24 and 48 weeks]
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5, evaluating synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (absent or present), bone edema (score 0-3), bone erosion (score 0-10) and bone proliferation/enthesophytes (absent or present).
- Swollen Joint Count (SJC) [24 and 48 weeks]
Change from baseline in the joints deemed swollen as per the joint count assessment performed by physical exam
- Tender Joint Count (TJC) [24 and 48 weeks]
Change from baseline in the joints deemed tender as per the joint count assessment performed by physical exam
- Change from baseline in the Clinical Disease Activity Index for Psoriatic Arthritis (c-DAPSA) Score [24 and 48 weeks]
It is the result of a sum of the following measures: tender joints, swollen joints, subject's assessment of disease activity and pain.
- Change from baseline in Spondyloarthritis Research Consortium of Canada (SPARCC), in subjects with preexisting enthesopathy [24 and 48 weeks]
SPARCC is an outcome measure for the assessment of enthesitis. Tenderness (yes/no) will be assessed at 16 sites of tendon insertion
- Change from baseline in the Leeds Enthesitis Index (LEI), in subjects with preexisting enthesopathy [24 and 48 weeks]
LEI is a validated tool for the assessment of enthesitis in PsA patients. Tenderness (yes/no) will be assessed at 6 sites of tendon insertion.
- Proportion of subjects with baseline enthesitis whose enthesitis improves to 0 [24 and 48 weeks]
Resolution of enthesitis in subjects who presented with at least one site of enthesitis at baseline.
- Change from baseline in the LDI, in subjects with preexisting dactylitis [24 and 48 weeks]
Dactylitis is characterized by the swelling of the entire finger or toe. It will be assessed using the Leeds Dactylitis Index (LDI). LDI measures the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a tenderness score.
- Proportion of subjects with baseline dactylitis whose dactylitis count improves to 0 [24 and 48 weeks]
Resolution of dactylitis in subjects who presented with at least one site of dactylitis at baseline.
- Change from baseline in the Psoriatic Arthritis Disease Activity Score (PASDAS) [24 and 48 weeks]
PASDAS is a weighted index comprising assessments of joints, function, acute phase response, QoL, and patient and physician visual analogue scores (VAS).
- Change from baseline in the Evaluator's global assessment of disease activity [24 and 48 weeks]
The Evaluator's Global Assessment of Disease Activity evaluates how active a subject's PsA is. A 0- to-10-unit numeric rating scale (NRS) will be used, on which the left-hand box of 0 represents "not active," and the right-hand box represents "extremely active".
- Change from baseline in the Subject's global assessment of disease activity [24 and 48 weeks]
The Subject's Global Assessment of Disease Activity evaluates how active a subject's PsA was on average during the past week. A 0- to-10-unit numeric rating scale (NRS) will be used, on which the left-hand box of 0 represents "doing very well," and the right-hand box represents "doing very poor".
- Change from baseline in the Subject's assessment of pain [24 and 48 weeks]
Subject's assessment of how much pain he/she had, on average, during the past week in his/her joints due to PsA. The subject will be asked to mark on a 0- to 10-unit NRS, on which the left-hand box of 0 represents "no pain," and the right-hand box represents the pain as bad as you can imagine".
- Change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) [24 and 48 weeks]
HAQ-DI is a 20-question, self-administered instrument that measures the subject's functional ability on a 4-level difficulty scale (0 to 3, with 0 representing normal or no difficulty; and 3 representing an inability to perform).
- Change from baseline in the WB-MRI Peripheral Enthesitis Inflammation Index [24 and 48 weeks]
Peripheral enthesitis inflammation index assessed by Whole-body magnetic resonance imaging (WB-MRI)
- Change from baseline in the WB-MRI Peripheral Joints Inflammation Index [24 and 48 weeks]
Peripheral joints inflammation index assessed by Whole-body magnetic resonance imaging (WB-MRI)
- Change from baseline in the WB-MRI Total Peripheral Inflammation Index [24 and 48 weeks]
Total peripheral (joints and enthesitis) inflammation index assessed by Whole-body magnetic resonance imaging (WB-MRI)
- Change from baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [24 and 48 weeks]
BASDAI is a composite score based on a subject self-administered survey of six questions using a 0- to 10-unit NRS that assesses the subject's five major symptoms relevant to spondyloarthropathies: 1) fatigue; 2) spinal pain; 3) peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening
- Change from baseline in the Psoriatic Arthritis Impact of Disease 12 domains (PsAID-12) [24 and 48 weeks]
PsAID-12 is a validated score reflecting the impact of disease in PsA. The PsAID-12 is a 12-item, self-administered questionnaire that reflects the impact of PsA from the perspective of the patient. It is composed of 12 physical and psychological domains.
- Adverse Events (AEs) [From enrollment until at least 28 days after completion of study treatment]
Number of participants with adverse event
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
-
Males or females, aged ≥ 18 years at time of consent
-
For all regions, the local Regulatory Label for treatment with apremilast must be followed.
-
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 PsA of ≥ 3 months AND ≤ 5 years in duration, meeting the CASPAR criteria for PsA at the time of Screening Visit
-
Have ≥ 3 swollen AND ≥ 3 tender joints, with hand involvement (defined as ≥ 1 swollen joint or dactylitis [each clinically active joint of a dactylitic digit is counted as one joint]).
-
Have at least 1 active enthesitis site (one of the SPARCC or LEI sites)
-
Must not have been treated previously with a TNF blocker or other biologic drug for PsA treatment
-
Must not have been treated with more than 2 csDMARDs
-
Subjects taking csDMARDs, with the exception of MTX, cyclosporine, or LEF, do not require a washout period. However, they must discontinue the csDMARD treatment at least one day prior to their Baseline Visit (ie, Visit 2, Day 1)
-
Subjects who have been previously treated with MTX for < 6 months and who are not on stable doses for at least 3 months will require a 28-day washout prior to the Baseline Visit (ie, Visit 2, Day 1) to participate in the study
-
Subjects who have been previously treated with LEF will require a 12-week washout prior to the Baseline Visit (ie, Visit 2, Day 1), or treatment with cholestyramine, per LEF prescribing label (ie, 8 g cholestyramine 3 times daily for 11 days)
-
Subjects who have been previously treated with cyclosporine will require a 28-day washout prior to the Baseline Visit (ie, Visit 2, Day 1) to participate in the study
-
If taking MTX (≤ 25 mg/week), continuity of treatment will be allowed if duration of treatment is ≥ 6 months and on a stable dose for at least 3 months prior to the Baseline Visit (ie, Visit 2, Day 1)
-
If taking oral glucocorticoids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 4 weeks prior to the Baseline Visit (ie, Visit 2, Day 1)
-
If taking NSAIDs or narcotic analgesics, must be on stable dose for at least 4 weeks prior to Baseline Visit (ie, Visit 2, Day 1)
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A female of childbearing potential (FCBP)† must have a negative pregnancy test at screening and baseline. While on IP and for at least 28 days after taking the last dose of IP, a FCBP who engages in activity in which conception is possible must 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; 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 [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
† An FCBP is defined as a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
§ The female subject's chosen form of contraception must be effective by the time the female subject is screened into the study (for example, hormonal contraception should be initiated at least 28 days before screening).
- Must be in general good health (except for PsA) 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).
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
-
Contraindication to MRI examination including, but not limited to, intracranial metal clips, heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators, metal hip replacements, profound claustrophobia or inability to lie in the MRI machine in an appropriate position to obtain quality images, history of hypersensitivity to gadolinium contrast agent
-
Severe renal impairment (creatinine clearance of less than 30 mL per minute estimated by the Cockroft-Gault equation), which would prevent the use of gadolinium enhancement
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History of clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease
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Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
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Prior history of suicide attempt at any time in the subject's lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
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Pregnant or breast feeding
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Active substance abuse or a history of substance abuse within 6 months prior to screening
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History of allergy or hypersensitivity to any component of the IP
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History of rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption
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History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease)
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Active tuberculosis or a history of incompletely treated tuberculosis
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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 and the infection cured, at least 4 weeks prior to screening and no new or recurrent infections prior to the Baseline Visit
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Malignancy or history of malignancy or myeloproliferative or lymphoproliferative disease within the past 3 years, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
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Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following Baseline Visit
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Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or fibromyalgia
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Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease), which confounds the ability to interpret data from the study
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Prior treatment with any biologic DMARD
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Prior treatment with more than 2 csDMARDs
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Use of the following systemic therapy(ies) within 28 days of the Baseline Visit (ie, Visit 2, Day 1): cyclosporine or other calcineurin inhibitors, glucocorticoids exceeding 10 mg daily prednisone equivalent, as well as mycophenolate.
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Use of MTX within 4 weeks of the Baseline Visit (ie, Visit 2, Day 1), unless subject is on
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Use of LEF within 12 weeks of the Baseline Visit (ie, Visit 2, Day 1), unless subject has taken cholestyramine, 8 g three times daily 11 days after stopping LEF
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Previous treatment with a JAK inhibitor (including tyk2 inhibitor)
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Prior treatment with apremilast, or participation in a clinical study involving apremilast
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Use of intra-articular (IA) glucocorticoid injection within 8 weeks before the Baseline Visit (ie, Visit 2, Day 1).
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Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Doctors of Saint John's Medical Group | Santa Monica | California | United States | 90404 |
| 2 | Inland Rheumatology Clinical Trials Inc | Upland | California | United States | 91786 |
| 3 | Malcom Randall VA Medical Center | Gainesville | Florida | United States | 32610 |
| 4 | Integral Rheumatology and Immunology Specialists | Plantation | Florida | United States | 33324 |
| 5 | NYU Langone Medical Center | New York | New York | United States | 10003 |
| 6 | Austin Regional Clinic | Austin | Texas | United States | 78731 |
| 7 | Swedish Medical Center | Seattle | Washington | United States | 98104 |
| 8 | Medizinische Universitat Wien | Vienna | Austria | 1090 | |
| 9 | UZ Leuven | Leuven | Belgium | 3000 | |
| 10 | University of Calgary - Cumming School of Medicine | Calgary | Alberta | Canada | T2N 4N1 |
| 11 | Alberta Rheumatology | Edmonton | Alberta | Canada | T5M 0H4 |
| 12 | Ottawa Hospital Research Institute | Ottawa | Ontario | Canada | K1H 7W9 |
| 13 | G.R.M.O. (Groupe de recherche en maladies osseuses) Inc. | Quebec | Canada | G1V 3M7 | |
| 14 | Aalborg Universitetshospital | Aalborg | Denmark | 9000 | |
| 15 | Frederiksberg Hospital | Frederiksberg | Denmark | 2000 | |
| 16 | Copenhagen University Hospital Rigshospitalet | Glostrup | Denmark | 2600 | |
| 17 | Universitaetsklinikum Bonn | Bonn | Germany | 53127 | |
| 18 | Universitaetsklinikum Duesseldorf | Duesseldorf | Germany | 40225 | |
| 19 | Johann Wolfgang Goethe University Hospital | Frankfurt am Main | Germany | 60590 | |
| 20 | Universitaetsklinikum Tuebingen | Tuebingen | Germany | 72076 | |
| 21 | Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele Ospedale Vittorio Emanuele | Catania | Italy | 95123 | |
| 22 | Azienda Ospedaliera Regionale San Carlo | Potenza/Matera | Italy | 85100 | |
| 23 | Udmurt Republic Republican Clinical Diagnostic Center | Izhevsk | Russian Federation | 426009 | |
| 24 | Research Institute of Rheumatology named after V.A.Nasonova | Moscow | Russian Federation | 115522 | |
| 25 | LLC Medical Center Zdorovaya Semiya | Novosibirsk | Russian Federation | 630061 | |
| 26 | Mechnikov North-Western State Medical University | Saint-Petersburg | Russian Federation | 191015 | |
| 27 | Regional Clinical Hospital No 1 - Tyumen | Tyumen | Russian Federation | 625032 | |
| 28 | Hospital Virgen de Macarena | Sevilla | Andalucía | Spain | 41009 |
| 29 | Hospital Santa Creu I Sant Pau | Barcelona | Spain | 08041 | |
| 30 | Hospital La Paz | Madrid | Spain | 28046 | |
| 31 | Kantonsspital Aarau - KSA | Aarau | Switzerland | 5001 | |
| 32 | Hopital Universitaire Genevois - Beau-Sejour Hospital | Geneve | Switzerland | 1206 | |
| 33 | Kantonsspital St Gallen | Sankt Gallen | Switzerland | 9007 | |
| 34 | NHS Lothian, Western General Hospital | Edinburgh | United Kingdom | EH16 4TJ | |
| 35 | The Leeds Teaching Hospitals NHS Trust - Chapel Allerton Hospital | Leeds | United Kingdom | LS7 4SA | |
| 36 | Southampton University Hospitals NHS Trust | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CC-10004-PSA-014
- U1111-1223-9823
- 2018-002748-10