A Phase IIB, Multi-Dose, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo in the Treatment of Psoriatic Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 191
- 试验地点
- 20
- 主要终点
- Long-term Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, and AEs of Interest
研究概览
简要总结
The purpose of this study is to determine an optimal abatacept dosing regimen for the treatment of active arthritis due to psoriatic arthritis in patients who have had a prior inadequate response to disease-modifying antirheumatic drugs, including methotrexate and tumor necrosis factor alpha-blockade compounds.
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
- Double (Participant, Investigator)
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
- •Meeting classification criteria for psoriatic arthritis for a duration of disease of at least 3 months
- •Prior failure (inefficacy or intolerance) of therapy with disease-modifying antirheumatic drugs; if patient had prior failure of methotrexate, he or she must have been taking at least 15 mg per week for at least 2 months
- •If recent failure(inefficacy or intolerance) of a tumor necrosis factor α-blockade compound, participant must be washed out prior to first dose: 56 days for infliximab and 28 days for etanercept and adalimumab
- •Disease activity as defined by a tender joint count of ≥3, swollen joint count of ≥3, and clinically detectable synovitis at screening and Day 01 (prior to infusion)
- •Active psoriasis with a qualifying target lesion ≥2 cm in diameter
- •Able to undergo magnetic resonance imaging
- •Use of appropriate birth control by women of child bearing potential (WOCBP)
排除标准
- •WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last dose of investigational product
- •Women who are pregnant or breastfeeding or who plan to become pregnant or to start breastfeeding during the duration of the study
- •Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- •Participants scheduled for or anticipating joint replacement surgery.
- •Those with a recent history of clinically significant drug or alcohol abuse
- •Concomitant illness that in the investigator's opinion is likely to require systemic glucocorticosteroid therapy during the study (for example: moderate to severe asthma)
- •Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, pulmonary, cardiac, neurologic, ophthalmologic, or cerebral disease.
- •Unwillingness or inability to undergo screening based on current local or country guidelines/standards to evaluate the presence of cancer
- •Cancer within the last 5 years
- •Current malignancy or signs of possible malignancy detected by screening procedures for which the workup to exclude malignancy has not been completed or malignancy cannot be excluded
- •At risk for or history (within 3 years) of tuberculosis
- •Any serious bacterial infection within the last 3 months, not treated and resolved with antibiotics, or any chronic bacterial infection (such as, but not limited to, chronic pyelonephritis, osteomyelitis, and bronchiectasis)
- •Evidence of active or latent bacterial or viral infection infections at the time of potential enrollment
- •Herpes zoster or cytomegalovirus resolving less than 2 months prior to signing informed consent
- •Receipt of any live vaccines within 3 months of the anticipated first dose of study medication or anticipation of the need for a live vaccine at any time during and for 3 months after the duration of the study
- •Long-term period participants: Must have met eligibility criteria for short-term period and completed short-term (24-week) period of the study
研究组 & 干预措施
Abatacept (30/10)
Abatacept (30 mg/kg) was administered as intravenous (iv) infusion over approximately 30 minutes on Days 1 and 15, followed by 10 mg/kg (fixed dose) abatacept infusion on Day 29 and every 28 days thereafter up to and including Day 141. The dose was calculated based on screening visit weight of participants for dosing on Days 1 and 15 followed by fixed dosing as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg) thereafter.
干预措施: Abatacept (Drug)
Abatacept (10/10)
Abatacept (10 mg/kg) was administered as iv infusion over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141 in the double-blind period and continued for next 18 months in the open-label period till Day 729. All participants received a dose based on their screening visit weight as per rheumatoid arthritis label (participants weighing <60 kg received 500 mg, participants weighing 60 to 100 kg received 750 mg, and participants weighing >100 kg received 1000 mg).
干预措施: Abatacept (Drug)
Abatacept (3/3)
Abatacept (3 mg/kg) was administered as iv infusion over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. The dose was calculated based on screening visit weight of participants.
干预措施: Abatacept (Drug)
Placebo
Placebo solution (5% dextrose in water for injection, 0.9% sodium chloride injection) by iv infusion was administered on Days 1, 15, and 29 and every 28 days thereafter till Day 141.
干预措施: Placebo (Drug)
结局指标
主要结局
Long-term Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, and AEs of Interest
时间窗: From Day 169 to Day 729
Presp=prespecified; acute= ≤1 hour after start of infusion; periinfusional= ≤24 hours after start of infusion. AE=any new unfavorable symptom or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=an unfavorable medical event that at any dose results in death, significant disability, drug dependency/abuse, hospitalization or prolonged hospitalization; is life-threatening, an important medical event, or a congenital anomaly/birth defect. Drug-related=possibly, probably, or certainly related and of unknown relationship to study drug.
Short-term Period: Number of Participants With ACR 20 Response at Day 169
时间窗: At Day 169 from Baseline
An ACR 20 responder was a participant who had a reduction of 20% or more from baseline in scores for both tender and swollen joints and had a reduction from baseline of 20% or more in 3 out of the following 5 assessments: participant's assessment of disease activity, participant's global assessment of disease activity, investigator's global assessment of disease activity, participant's assessment of physical function by HAQ-DI, and Disease Activity Score 28-C reactive protein.
次要结局
- Long-term Period: Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR 50, ACR 70, ACR 90 Responses at Days 365 and 729(At Days 365 and 729 from Baseline)
- Long-term Period: Number of Participants With an Investigators Global Assessment (IGA) Score of Clear or Almost Clear at Days 365 and 729(From Day 169 to Days 365 and 729)
- Long-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Days 365 and 729(From Baseline to Days 365 and 729)
- Long-term Period: Mean Change From Baseline in the Short-form 36 (SF-36), Version 2, Domain and Component Scores at Days 365 and 729(At Days 365 and 729 from baseline)
- Long-term Period: Number of Participants Achieving A Reduction of At Least 0.3 Unit From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Days 365 and 729(Days 365 and 729 from baseline)
- Short-term Period: Number of Participants With Marked Abnormalities in Hematology(From Baseline to Day 169)
- Short-term Period: Number of Participants With Marked Abnormalities in Hematology (Continued)(From Baseline to Day 169)
- Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry(Baseline to Day 169)
- Short-term Period: Number of Participants With Marked Abnormalities in Serum Chemistry (Continued)(From Baseline to Day 169)
- Short-term Period: Number of Participants With Marked Abnormalities in Urinalysis(From Baseline to Day 169)
- Short-term Period: Number of Participants Who Died and With SAEs, AEs, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Drug-related AEs, and Drug-related SAEs(From Baseline to Day 169)
- Short-term Period: Number of Participants With an IGA Score of Clear or Almost Clear at Day 169(At Day 169 from Baseline)
- Short-term Period: Mean Percentage of Change From Baseline in Target Lesion Score at Day 169(At Day 169 from Baseline)
- Short-term Period: Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies (Anti-Abatacept-C)(From Baseline to Day 169)
- Short-term Period: Mean Change From Baseline in the Mental Component Summary Score as Measured by the Short-form 36 at Day 169(At Day 169 from Baseline)
- Short-term Period: Mean Serum Concentrations of Abatacept(Days 1, 15, 29, 57, 85, 113, 141, and 169)
- Short-term Period: Mean Serum Trough Concentrations (Cmin) of Abatacept(Days 1, 15, 29, 57, 85, 113, 141, and 169)
- Short-term Period: Population Pharmacokinetic (POPPK) Analysis of the Pharmacokinetic (PK) Parameters(Days 1, 15, 29, 57, 85, 113, 141, and 169)
- Short-term Period: Mean Change From Baseline in Physical Component Summary Score as Measured by the Short-form 36 at Day 169(At Day 169 from Baseline)
- Short-term Period: Number of Participants Achieving a Reduction of At Least 0.3 Unit From Baseline in HAQ-DI Scores at Day 169(At Day 169 from Baseline)