A Phase 2, 24-Week, Randomized, Double-blind, Placebo-controlled, Multicenter Study, With an 80-Week Active Treatment Extension, to Evaluate the Efficacy and Safety of CC-90001 in Subjects With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 138
- 试验地点
- 112
- 主要终点
- Percentage Point Difference in % Predicted Forced Vital Capacity (FVC).
研究概览
简要总结
This is a Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, pharmacokinetics (PK), quality of life and exploratory pharmacodynamics (PD) of two treatment doses of CC-90001, 200 mg and 400 mg, compared with placebo, when delivered once daily per os (PO) in subjects with idiopathic pulmonary fibrosis (IPF). This study is designed to assess response to treatment by using measures of lung function, disease progression, fibrosis on radiography, and patient-reported outcomes. It will also assess dose response.
详细描述
Approximately 165 adult male and female subjects with a confirmed diagnosis of Idiopathic pulmonary fibrosis (IPF) (according to the most recent IPF guideline for diagnosis and management) will be randomized 1:1:1 (55 subjects per arm) to treatment with oral CC-90001or matching placebo for an initial 24 weeks.
The randomization will be stratified based on the concurrent administration of SOC (Yes/No). Subjects completing the 24-week Double-blind Treatment Phase will continue onto the 80-week Active Treatment Extension Phase. At Week 24, all subjects originally randomized to receive placebo will be re-randomized 1:1 to blinded CC-90001 (200 mg or 400 mg PO QD). During the 80-week Active Treatment Extension Phase, all subjects not on concurrent SOC therapy will have the opportunity, if deemed appropriate by the Investigator, to receive allowed standard of care (SOC).
The exploratory Progressive Pulmonary Fibrosis (PPF) sub study will evaluate the efficacy, safety, PK, quality of life and exploratory PD of one PO treatment dose regimen of CC-90001, compared with placebo, for an initial 24 weeks of treatment, in subjects with PPF and long-term safety in the 80-week Active Treatment Extension Phase when all PPF subjects will receive CC-90001. Approximately 45 non-SOC subjects will be randomized in this sub study.
All subjects who complete the study treatment phases and those subjects who discontinue investigational product (IP) prior to the completion of the study will participate in the 4-week Post-treatment Observational Follow-up Phase.
The study will be conducted in compliance with the International Council Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject understands and has voluntarily signed and dated an informed consent form
- •Subject is male or female ≥ 40 years of age
- •Diagnosis of IPF is supported by HRCT and historical lung biopsy (surgical lung biopsy [SLB] or cryobiopsy) if available according to guidelines.
- •No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar lavage (BAL), or SLB, if performed.
- •Percent predicted forced vital capacity (% FVC) ≥ 45% and ≤ 95% at Screening
- •Percent predicted diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 25% and ≤ 90% predicted at Screening.
- •Able to walk ≥ 150 meters during the 6-minute walk test (6MWT) at Screening
- •Females of childbearing potential (FCBP) must commit to true abstinence or agree to use two effective birth control methods.
- •Male subjects must practice true abstinence or use a barrier method of contraception.
- •Additional inclusion criteria apply.
- •Progressive Pulmonary Fibrosis (PPF) Sub-Study:
- •Met all inclusion criteria described for IPF subjects other than Inclusion Criterion
- •Features of diffuse fibrosing lung disease of > 10% on HRCT by central reading.
- •Investigator-documented ≥ 5% annualized relative decline in FVC in past 24 months from Screening Visit 1
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Subject with a QTcF > 450 msec.
- •Evidence of clinically relevant airways obstruction at Screening.
- •Subjects using therapy targeted to treat IPF.
- •History of latent or active TB, unless there is medical record documentation of successful completion of a standard course of treatment
- •History of hepatitis B and/or hepatitis C, including those considered successfully treated/cured
- •Pregnancy or lactation.
- •Additional exclusion criteria apply.
研究组 & 干预措施
Placebo PO QD
55 subjects will be randomized to placebo
干预措施: Placebo (Other)
CC-90001 400 mg PO QD
55 subjects will be randomized to CC-90001 400mg
干预措施: CC-90001 (Drug)
CC-90001 200 mg PO QD
55 subjects will be randomized to CC-90001 200mg
干预措施: CC-90001 (Drug)
CC-90001 400 mg PO QD- Sub-Study
30 subjects will be randomized to CC-90001 400mg
干预措施: CC-90001 (Drug)
Placebo PO QD- Sub-Study
15 subjects will be randomized to placebo
干预措施: Placebo (Other)
结局指标
主要结局
Percentage Point Difference in % Predicted Forced Vital Capacity (FVC).
时间窗: from baseline to week 24
Mean change from baseline in percentage point difference in % predicted forced vital capacity (FVC) FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment.
次要结局
- Mean Change From Baseline in Absolute Forced Vital Capacity (FVC).(from baseline to week 24)
- Mean Change in Distance Walked in the 6-minute Walk Test (6MWT)(From baseline up to week 104)
- Mean Change From Baseline in Dyspnea Rating on Borg Scale(From baseline up to week 104)
- Percentage of Participants Who Had Disease Progression(From Baseline up to week 24)
- Mean Change From Baseline in Total Score and Domains on the Saint George's Respiratory Questionnaire (SGRQ)(From Baseline up to week 24)
- Mean Change From Baseline in The University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ)(From Baseline up to week 24)
- Number of Participants With Adverse Events at the End of the Active Treatment Phase(From re-randomization to end of treatment (approximately 84 weeks))
- Number of Participants With Adverse Events in the Placebo Controlled Period(from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort))
- Number of Participants With Worst Changes in Hematology Laboratory Parameters During the Active Treatment Extension Period(From re-randomization to end of treatment (approximately 84 weeks))
- Number of Participants With Worst Changes in Hematology Laboratory Parameters During the in the Placebo Controlled Period(from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort))
- Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Active Treatment Extension Period(From re-randomization to end of treatment (approximately 84 weeks))
- Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Placebo Controlled Period(from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort))
- Mean Change From Baseline in Electrocardiogram Measurements in the Active Treatment Extension Period(From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks))
- Mean Change From Baseline in Electrocardiogram Measurements in the Placebo Controlled Period(from baseline to week 24)
- Number of Participants With Worst Increase From Baseline in Blood Pressure in the Active Extension Period(From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks))
- Number of Participants With Worst Increase From Baseline in Blood Pressure in the Placebo-controlled Period(from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort))