A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Dose Regimens of CC-10004 in Subjects With Active Psoriatic Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 204
- 试验地点
- 37
- 主要终点
- Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12
研究概览
简要总结
This study is to look at the preliminary efficacy and safety of 2 dose regimens of apremilast (20 mg twice a day and 40 mg once a day) versus placebo in patients with active psoriatic arthritis.
详细描述
Prior to the implementation of Amendment 1/UK3 the study consisted of 3 phases - pre-randomization up to 35 days, up to 84 days placebo-controlled treatment and a 28-day observational follow up. After the implementation of Amendment 1/UK3, the study consisted of 4 phases - pre-randomization up to 35 days, up to 84 days treatment in the placebo controlled treatment phase, up to 84 days treatment in the active treatment extension phase and a 28 day follow up. Participants who completed the treatment phase prior to implementation of amendment 1/UK3 did not have the option of entering the extension phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months
- •Active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints
- •Negative rheumatoid factor (RF)
- •If using methotrexate, be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study
- •If using oral corticosteroids, be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study
- •If using nonsteroidal anti-inflammatory drug (NSAID) therapy, be on a stable dose for at least 14 days prior to screening and throughout the study
- •Must meet the following laboratory criteria:
- •Hemoglobin ≥ 9 g/dL
- •Hematocrit ≥ 27%
- •White blood cell (WBC) count ≥ 3000/μL (≥ 3.0 X 10^9/L) and < 20,000/μL (< 20 X 10^9/L)
- •Neutrophils ≥ 1500 /μL (≥ 1.5 X 10^9/L)
- •Platelets ≥ 100,000 /μL (≥ 100 X 10^9/L)
- •Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
- •Total bilirubin ≤ 2.0 mg/dL
- •Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x upper limit of normal (ULN)
- •Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO adequate forms of contraception while on study medication. A FCBP must agree to have pregnancy tests every 28 days while on study medication
- •Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication
排除标准
- •History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- •Pregnant or lactating female
- •History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
- •History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T SPOT®.TB, QuantiFERON Gold®])
- •Clinically significant abnormality on the chest x-ray (CXR) at screening
- •Current erythrodermic, guttate, or pustular forms of psoriasis
- •History of infected joint prosthesis within the past 5 years
- •Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
- •Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients [eg, Eucerin®] and tar shampoo are also allowed.)
- •Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization
- •Etanercept use within 56 days prior to randomization
- •Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
- •Alefacept use within 168 days (24 weeks) prior to randomization
- •Use of intra-articular corticosteroids within 28 days prior to randomization
- •Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
- •Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
- •High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
- •History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
- •Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis
研究组 & 干预措施
Apremilast 40 mg QD
Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks.
The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.
干预措施: Apremilast (Drug)
Apremilast 20 mg BID
Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.
干预措施: Apremilast (Drug)
Placebo
Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase. Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12
时间窗: Baseline and Week 12
A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal \[CMC\] and the distal interphalangeal \[DIP\] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders.
次要结局
- Percentage of Participants With a Modified ACR 50 Response at Week 12(Baseline and Week 12)
- Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12(Baseline and Week 12)
- Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12(Week 12)
- Number of Participants With Adverse Events Leading to a Dose Reduction(Baseline to Week 12)
- Time to ACR 70 Response During the Treatment Phase(Baseline to Week 12)
- Number of Participants With Adverse Events During the Treatment Phase(12 weeks)
- Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12(Baseline and Week 12)
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12(Baseline and Week 12)
- Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12(Week 12)
- Maximal ACR Response During the Treatment Phase(ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12)
- Change From Baseline in Dactylitis Severity Score at Week 12(Baseline and Week 12)
- Percentage of Participants With Enthesitis(Baseline and Week 12)
- Percentage of Participants With a Modified ACR 70 Response at Week 12(Baseline and Week 12)
- Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy(Baseline to Week 12)
- Time to ACR 50 Response During the Treatment Phase(Baseline to Week 12)
- Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12(Baseline and Week 12)
- Number of Participants With Adverse Events During the Extension Phase(Weeks 12 to 24 (Extension Phase))
- Time to ACR 20 Response During the Treatment Phase(Baseline to Week 12)
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24(Baseline and Week 24)
- Time to ACR 50 Response During the Treatment and Extension Phase(Baseline to Week 24)
- Time to ACR 70 Response During the Treatment and Extension Phase(Baseline to Week 24)
- Change From Baseline and Week 12 in SF-36 at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)
- Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase(From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).)
- Number of Participants Who Relapsed During the Observational Follow-up Phase(28-day observational follow-up period following Week 12)
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12(Baseline and Week 12)
- Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)
- Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12(Baseline and Week 12)
- Percentage of Participants With a Modified ACR 70 Response at Week 24(Baseline (Day 1) and Week 24)
- Maximal ACR Response During the Extension Period(ACR was measured at Baseline and Weeks 16, 20 and 24)
- Percentage of Participants With Enthesitis in the Extension Phase(Week 12 and Week 24)
- Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12(Baseline and Week 12)
- Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24(Baseline and Week 24)
- Percentage of Participants With a Modified ACR 20 Response at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)
- Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24(Baseline and Week 24)
- Time to ACR 20 Response During the Study(Baseline to Week 24)
- Time to Relapse of Psoriatic Arthritis After Extension Phase(From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).)
- Percentage of Participants With a Modified ACR 50 Response at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)
- Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24(Baseline, Week 12 and Week 24)
- Number of Participants Who Relapsed After the Extension Phase(Week 24 to Week 28 (28-day follow-up period))
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24(Baseline (Day 1), Week 12 (Day 85) and Week 24)