Safety and Tolerability Study in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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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 moderate to severe IPF patients. MN-001 750 mg or matching placebo will be orally administered twice daily over a 26 week period in subjects with a confirmed diagnosis of IPF per the ATS )American Thoracic Society) 2011 Guidelines. Approximately 15 subjects are planned to be enrolled. This study will consist of two treatment arms, MN-001 and matching placebo. Randomization will occur in a 2:1 ratio (MN-001: placebo). Eligible subjects will consist of males and females ranging in age from 21 to 80 years old, inclusive. The study will consist of a Screening Phase (up to 3 months prior to Day1) followed by a 26 week double-blind Treatment Phase, a 26 week Open-Label Extension (OLE) phase and a Follow-up Visit (within 4 weeks after the last dose).

Official Title
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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)

Conditions
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IPF, Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: tipelukast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double-Blind Treatment<br>Subjects who complete all of the screening assessments and meet all inclusion/exclusion criteria will be started on MN-001 (tipelukast) 750 mg or matching placebo bid. Subjects will return to the clinic on Treatment Day 1 to receive their first dose of study medication. Subsequently, subjects will return to the clinic on a regular basis for 26 weeks. During the Treatment Phase, safety and efficacy parameters will be assessed and concomitant medications will be documented. The safety and tolerability of MN-001 will be evaluated by an Independent Safety Monitor during this phase. | Drug: tipelukast<br>* A novel, orally bioavailable small molecule compound that demonstrates anti-inflammatory and anti-fibrotic activity<br>* Other names: MN-001;Drug: Placebo<br>* Excipients of MN-001/tipelukast<br>|
| Other: Open-Label Extension<br>Upon completion of the Double-blind Treatment Phase, subjects who were taking placebo, will participate in the open-label extension (OLE) phase for an additional 6 months. Subjects randomized to the MN-001 (tipelukast) group will continue the study drug for additional 6 months. | Drug: tipelukast<br>* A novel, orally bioavailable small molecule compound that demonstrates anti-inflammatory and anti-fibrotic activity<br>* Other names: MN-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of FVC (forced vital capacity) at 26 weeks |  | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of MN-001 in subjects with IPF assessed by number of adverse events experienced by each participant |  | Subjects will return to the clinic at Months 1, 3, 6, and will be followed by telephone at Week 1 and Month 4 | 
| Tolerability of MN-001 in subjects with IPF assessed by number of adverse events experienced by each participant |  | Subjects will return to the clinic at Months 1, 3, and 6 and will be followed by telephone at Week 1 and Month 4 | 
| Rate of decline on disease activity based on the 6-minute walk test |  | The rate of decline on disease activity will be assessed at the 26-week visit | 
| Change from baseline on disease activity based on Modified Medical Research Council Dyspnea Score (MMRC) |  | The change from baseline on disease activity will be assessed at the 26-week visit | 
| Change from baseline on quality of life (QOL) measured by A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF) |  | The change from baseline on QOL will be assessed at the 26-week visit | 
| Frequency of worsening IPF based on 6-minute walk test score |  | Worsening of IPF will be assessed at Screening, Month 3, Month 6, Month 9 and Month 12. | 
| Frequency of worsening IPF based on Modified Medical Research Council Dyspnea Score (MMRC) |  | Frequency of worsening IPF will be assessed at Screening, Month 3, Month 6, Month 9 and Month 12. | 
| Time to first worsening IPF based on MMRC score |  | Time to first worsening IPF will be assessed at Screening, Month 3, Month 6, Month 9 and Month 12. | 
| Time to first worsening IPF based on 6MWT score |  | Time to first worsening IPF will be assessed at Screening, Month 3, Month 6, Month 9 and Month 12. | 
| Change from baseline of FVC (forced vital capacity) % predicted at 26 weeks |  | Change from baseline of FVC will be measured at 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IPF, tipelukast, fibrosis, Idiopathic Pulmonary Fibrosis