NCT03783026已完成4 期
A Phase 4, Multicenter, Single-Arm, Open-Label Study to Evaluate the Impact of Apremilast (CC-10004) on MRI Outcomes in Subjects With Active Psoriatic Arthritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 123
- 试验地点
- 36
- 主要终点
- Change From Baseline in the Composite Score of BME, Synovitis, and Tenosynovitis Assessed by PsAMRIS at Week 24
研究概览
简要总结
This study is designed to assess the efficacy of apremilast, either in monotherapy or with stable methotrexate, on imaging outcomes in adults with active psoriatic arthritis with less than 5 years of disease duration (since diagnosis), and who are naïve to biologic therapies.
详细描述
This study consists of 3 phases:
-
Screening Phase - up to 4 weeks
-
Single-arm, Open-label Treatment Phase - Weeks 0 to 48
-
Participants will receive apremilast 30 mg BID (after a 5-day titration period) for the entire duration of this phase.
-
MRI of the most affected hand and whole body MRI (WB-MRI) will be performed at weeks 0, 24, and 48.
-
The hand with the greater inflammatory burden of swollen joints and/or dactylitis will be considered as the most affected hand. If both hands are equally affected, the dominant hand will be designated as the index hand.
-
Observational Follow-up Phase - 4 Weeks
-
All participants who complete the study or discontinue early will participate in the 4-week Post-Treatment Observational Follow-up Phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Classification Criteria for Psoriatic Arthritis (CASPAR) 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 Spondyloarthritis Research Consortium of Canada [SPARCC] or Leeds Enthesitis Index [LEI] sites)
- •Must not have been treated previously with a tumor necrosis factor (TNF) blocker or other biologic drug for PsA treatment
- •Must not have been treated with more than 2 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)
- •Subjects taking csDMARDs, with the exception of methotrexate (MTX), cyclosporine, or leflunomide (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 to participate in the study
- •Subjects who have been previously treated with LEF will require a 12-week washout prior to the Baseline Visit, 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 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
- •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
- •If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must be on stable dose for at least 4 weeks prior to Baseline Visit
- •A female of childbearing potential (FCBP) must have a negative pregnancy test at screening and baseline. While on investigational product (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.
- •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).
排除标准
- •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
- •History of clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- •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.
- •Pregnant or breast feeding
- •Active substance abuse or a history of substance abuse within 6 months prior to screening
- •History of allergy or hypersensitivity to any component of the IP
- •History of rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption
- •History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease)
- •Active tuberculosis or a history of incompletely treated tuberculosis
- •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
- •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;
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following Baseline Visit
- •Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or fibromyalgia
- •Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, rheumatoid arthritis, ankylosing spondylitis, Lyme disease), which confounds the ability to interpret data from the study
- •Prior treatment with any biologic DMARD
- •Prior treatment with more than 2 csDMARDs
- •Use of the following systemic therapy(ies) within 28 days of the Baseline Visit: cyclosporine or other calcineurin inhibitors, glucocorticoids exceeding 10 mg daily prednisone equivalent, as well as mycophenolate.
- •Use of MTX within 4 weeks of the Baseline Visit, unless subject is on stable doses for at least 3 months and total treatment duration with MTX is ≥ 6 months
- •Use of LEF within 12 weeks of the Baseline Visit, unless subject has taken cholestyramine, 8 g three times daily 11 days after stopping LEF
- •Previous treatment with a Janus kinase (JAK) inhibitor (including tyrosine kinase 2 [TYK2] inhibitor)
- •Prior treatment with apremilast, or participation in a clinical study involving apremilast
- •Use of intra-articular (IA) glucocorticoid injection within 8 weeks before the Baseline Visit.
- •Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)
研究组 & 干预措施
Apremilast
Experimental
Participants will receive apremilast 30 mg twice a day for 48 weeks.
干预措施: Apremilast (Drug)
结局指标
主要结局
Change From Baseline in the Composite Score of BME, Synovitis, and Tenosynovitis Assessed by PsAMRIS at Week 24
时间窗: Baseline and week 24
PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis). Synovitis, flexor tenosynovitis, and bone marrow edema were scored from 0 (none/normal) to 3 (severe) at each joint. The total scores for synovitis and tenosynovitis range from 0 to 36 and the total score for BME ranges from 0 to 72 since both proximal and distal regions of each joint were scored. The PsAMRIS composite inflammation score is calculated as: BME score + 2 × synovitis score + 2 × tenosynovitis score, and ranges from 0 (normal) to 216 (severe). A negative change from baseline indicates improvement. This endpoint was analyzed using a mixed-effects model for repeated measures (MMRM) with change from baseline as the dependent variable; baseline value, scanner type and time as independent variables.
次要结局
- Change From Baseline in the Composite Score of BME, Synovitis, and Tenosynovitis Assessed by PsAMRIS at Week 48(Baseline and week 48)
- Percentage of Participants With Baseline Dactylitis Whose Dactylitis Count Improved to 0 at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in the Psoriatic Arthritis Disease Activity Score (PASDAS) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Composite Score of BME and Synovitis Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the PsAMRIS Total Inflammation Score at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Bone Marrow Edema Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Synovitis Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Tenosynovitis Assessed by PsAMRIS at Weeks 24 and 48(Baseline and Weeks 24 and 48)
- Change From Baseline in Bone Erosion Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Tender Joint Count (TJC) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Leeds Dactylitis Index (LDI) at Weeks 24 and 48 in Participants With Pre-existing Dactylitis(Baseline and weeks 24 and 48)
- Change From Baseline in Periarticular Inflammation Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Clinical Disease Activity Index for Psoriatic Arthritis (c-DAPSA) Score at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Leeds Enthesitis Index (LEI) at Weeks 24 and 48 in Participants With Pre-existing Enthesopathy(Baseline and weeks 24 and 48)
- Change From Baseline in the PsAMRIS Total Damage Score at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Bone Proliferation Assessed by PsAMRIS at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Swollen Joint Count (SJC) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index at Weeks 24 and 48 in Participants With Pre-existing Enthesopathy(Baseline and weeks 24 and 48)
- Percentage of Participants With Baseline SPARCC Enthesitis Whose Enthesitis Improved to 0 at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in the Evaluator's Global Assessment of Disease Activity at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Patient's Global Assessment of Disease Activity at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Subject's Assessment of Pain at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Percentage of Participants With Baseline LEI Enthesitis Whose Enthesitis Improved to 0 at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in Whole Body MRI (WB-MRI) Peripheral Enthesitis Inflammation Index at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the WB-MRI Peripheral Joints Inflammation Index at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the WB-MRI Total Peripheral Inflammation Index at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Change From Baseline in the Psoriatic Arthritis Impact of Disease 12 Domain Questionnaire (PsAID-12) at Weeks 24 and 48(Baseline and weeks 24 and 48)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug up to 28 days after last dose; up to 52 weeks.)
研究者
研究点 (36)
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