A Randomized, Placebo-Controlled, Double-Blind Six Month Study Followed by an Open-Label Extension Phase to Evaluate the Efficacy, Safety and Tolerability of MN-001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- MediciNova
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Absolute Change From Baseline in Forced Vital Capacity for 26 Weeks
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind, 6-month study followed by a 6-month open-label extension phase to evaluate the efficacy, safety, and tolerability of MN-001 in patients diagnosed with moderate to severe idiopathic pulmonary fibrosis (IPF). Participants were randomly assigned to receive MN-001 or matching placebo twice daily over a 26-week period. A total of 15 participants were enrolled.
详细描述
This study was a single-center, randomized (2:1), placebo-controlled, double-blind, 6-month study followed by a 6-month open-label extension (OLE) phase in patients with moderate to severe IPF. Major inclusion criteria: physician diagnosed IPF (ATS Guidelines, 2011), males and females aged 21 to 80 years, GAP Stage II-III; on no anti-fibrotic treatment. Patients on stable dose of nintedanib for at least 3 months prior to the study were allowed.
The study consisted of a Screening Phase (up to 3 months prior to Day1), a 26- week Double-Blind Treatment (DBT) period, a 26-week Open-Label Extension (OLE) period, and a Follow-up / End of Study Visit (within 4 weeks of the last dose taken).
A total of 15 patients were enrolled in the study. During the DBT period, participants were randomly assigned to receive MN-001 750 mg twice daily or a matching placebo in a 2:1 ratio (MN-001: placebo) for 26 weeks. During the OLE period, all participants received MN-001 750 mg twice daily for 26 weeks. Taken together, participants (n=15) received either MN-001 50 mg twice daily for 12 months (MN-001/MN-001) or matching placebo for 6 months and MN-001 750 mg twice daily for 6 months (Placebo/MN-001).
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)
盲法说明
The double-blind period is masked by the participants, care provider, investigator, and outcomes assessor.
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ages 21 to 80, inclusive
- •Presence of IPF confirmed per ATS criteria (2011)
- •Presence of moderate to severe disease, stage II-III defined by GAP index (Gender, Age and Physiology)
- •Subjects who are currently treated with OFEV™/Nintedanib should be on a stable dose for at least 3 months prior to initiation of the study drug.
- •Females of child-bearing potential must have a negative serum ß-hCG (human chorionic gonadotropin) at screening and must be willing to use appropriate contraception (as defined by the investigator) for the duration of study treatment and 30 days after the last dose of study treatment.
- •Males should practice contraception for the duration of study treatment and 30 days after the last dose of study treatment as follows: condom use and contraception by female partner.
- •Subject is in stable condition on the basis of medical history, physical examination, and laboratory screening, as determined by the investigator.
- •Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.
- •Written informed consent is obtained prior to participating the study.
排除标准
- •Expected to receive a lung transplant within 1 year from the start of the Treatment Phase or on a lung transplant waiting list at the start of the Treatment Phase.
- •Known explanation for interstitial lung disease
- •Subjects on OFEV™/Nintedanib with a dose interruption due to significant adverse events within 6 weeks of screening visits.
- •Ongoing IPF treatments with investigational therapy
- •Ongoing IPF treatments with Esbriet® (Pirfenidone)
- •Immunosuppressants (i.e., Mycophenolate, Imuran, Cyclophosphamide), and cytokine modulating agents within 1 month of Screening Visit and throughout the study
- •Use of antibiotics and systemic steroids due to IPF exacerbation within 1 month of Screening Visit
- •Clinically significant cardiovascular disease, including myocardial infarct within last 6 months, unstable ischemic heart disease, congestive heart failure or angina
- •Resting pulse < 50 bpm, SA (sinoatrial) or AV (atrioventricular) block, uncontrolled hypertension, or QTcF (QT interval corrected using the Fridericia formula) > 450 ms
- •Immune system disease
- •Any significant laboratory abnormality which, in the opinion of the Investigator, may put the subject at risk
- •History of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- •History or evidence of drug or alcohol abuse
- •History of HIV (human immunodeficiency virus) or other active infection.
- •Currently has a clinically significant medical condition including the following: neurological, psychiatric, immunological, metabolic, hepatic, hematological, pulmonary (other than IPF) , cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study.
- •Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Investigator, they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted.
- •CYP2C8 (cytochrome P450 isoenzyme C28) and CYP2C9 (cytochrome P450 isoenzyme C29) substrates with narrow therapeutic indices (i.e. paclitaxel, phenytoin and S-warfarin) within 14 days of Screening Visit and throughout the study.
- •Beta blockers within 14 days of Screening Visit and throughout the study
- •Macrolide or quinolone class antibiotics within 14 days of Screening Visit and throughout the study.
- •Poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.
- •Currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent.
- •Unwilling or unable to conduct Spirometry (Vital Capacity) test.
- •Unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or is planning to relocate during the study.
研究组 & 干预措施
MN-001 in Double-blind period for 26 weeks, then MN-001 in Open-Label period for 26 weeks
MN-001 750 mg twice a day during the double-blind period (26 weeks) and MN-001 750 mg twice a day during the open-label period for 26 weeks. The arm title is shortened to MN-001/MN-001 for all results sections.
干预措施: MN-001 (Drug)
Placebo during Double-blind period for 26 weeks, then MN-001 in Open-Label period for 26 weeks
Placebo twice a day during the double-blind period for 26 weeks and MN-001 750 mg twice daily during the open-label period for 26 weeks. The arm title is shortened to Placebo/MN-001 for all results sections.
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change From Baseline in Forced Vital Capacity for 26 Weeks
时间窗: Baseline and Week 26 at the end of Double-blind treatment period.
Predicted forced vital capacity (FVC) is a reference value for lung function based on your age, height, sex, and ethnicity measured by a spirometer and is an established method of pulmonary function. FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters (L).
Percent Change in Forced Vital Capacity From Baseline to Week 26
时间窗: Baseline, and Week 26 at the endpoint of the Double-blind treatment period.
FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters (L). The mean relative change was calculated as 100\*\[FVC (L) at Week 26 - FVC (L) at baseline\].
Absolute Change From Baseline in Forced Vital Capacity (% Predicted)
时间窗: Baseline and Week 26 at the end of Double-blind treatment period.
FVC(%pred.) refers to the expected FVC for a healthy individual with the same age, sex, height, and weight. The actual FVC result is then expressed as a percentage of this predicted value; values of 80% or higher are generally considered normal and indicate no significant impairment.
Relative Change From Baseline in Percent Predicted Forced Vital Capacity From Baseline to Week 26
时间窗: Baseline and Week 26 at the end of Double-blind treatment period.
FVC (%pred/) refers to the expected FVC for a healthy individual with the same age, sex, height, and weight. The actual FVC result is then expressed as a percentage of this predicted value; values of 80% or higher are generally considered normal and indicate no significant impairment. Relative change is measured as percent (%) change from FVC (%pred.).
Semiannual Rate of Decline of Disease Activity Based on Forced Vital Capacity
时间窗: Baseline and Week 26 at the end of Double-blind treatment period.
The semiannual rates of change in FVC, measured in liters, were estimated using simple linear regression, with time measured in half-years.
次要结局
- Number of Participants With Treatment-related Serious Adverse Events.(Baseline, and Week 26 at the endpoint of the Double-blind treatment period)
- Change From Baseline on Disease Activity Based on Modified Medical Research Council Dyspnea Score(Baseline, and Week 26 at the endpoint of the Double-blind treatment period)
- Change From Baseline on Quality of Life (QOL) Measured by A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis(Baseline, and Week 26 at the endpoint of the Double-blind treatment period)
- Frequency of Worsening IPF(Baseline, and Week 26 at the endpoint of the Double-blind treatment period)