Idiopathic Pulmonary Fibrosis, IPF
Conditions
Keywords
tipelukast, IPF, fibrosis, Idiopathic Pulmonary Fibrosis
Brief summary
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.
Detailed description
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).
Interventions
DRUGMN-001
A novel, orally bioavailable small molecule compound that demonstrates anti-inflammatory and anti-fibrotic activity
DRUGPlacebo
Excipients of MN-001/tipelukast
Sponsors
MediciNova
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The double-blind period is masked by the participants, care provider, investigator, and outcomes assessor.
Intervention model description
This study evaluated the efficacy, safety, and tolerability of MN-001 in male and female patients aged 21 to 80 years, inclusive, with moderate-to-severe idiopathic pulmonary fibrosis (IPF). Fifteen (15) participants received MN-001 750 mg or a matching placebo twice daily for 26 weeks in a 2:1 (MN-001:Placebo) ratio. The study consisted of a Screening period (up to 3 months before baseline), a 26-week double-blind treatment (DBT) period, a 26-week open-label (OL) treatment period, and a follow-up visit (within 4 weeks after the last dose). Efficacy results are reported only for the DBT period. Safety findings are reported from Baseline (Day 1 of MN-001 or placebo treatment) to the end of the Open-Label period (52 weeks total).
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Forced Vital Capacity for 26 Weeks | 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 | 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) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Serious Adverse Events. | Baseline, and Week 26 at the endpoint of the Double-blind treatment period | Treatment-related serious adverse events (TRSAEs) are defined as possibly related, probably related, or related to MN-001 treatment. |
| 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 | The Modified Medical Research Council Dyspnea Score is a simple grading system widely used in the assessment of dyspnea (difficulty breathing) in chronic respiratory diseases, such as IPF. The breathlessness scale comprises five statements that cover respiratory disability from 0 (zero) to 4, in which 0 = not troubled by breathlessness, except on strenuous exercise, 1= shortness of breath when hurrying on the level or walking up a slight hill, 2 = walks slower than people of the same age or has to stop for breath when walking at own pace on level ground, 3 = stops for breath after walking just 100 meters (100 yards) or after a few minutes, and 4 = too breathless to leave the house or breathless when dressing or undressing. A higher score corresponds to greater difficult in breathing. |
| 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 | The A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis score is a quality-of-life questionnaire that has 13 domains (cough, dyspnea, forethought, sleep, mortality, exhaustion, emotional well-being, social participation, finances, independence, sexual health, relationships, therapy). The domain scores and the Total score from these domain scores are calculated by summation. Higher scores correspond to greater impairment. The Total score ranges from 74 to 370. |
| Frequency of Worsening IPF | Baseline, and Week 26 at the endpoint of the Double-blind treatment period | The number of participants who experienced worsening in IPF. Worsening of IPF is defined as acute IPF exacerbation, hospitalization due to respiratory symptoms, IPF-related fatal events, and/or lung transplantation. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRebecca Bascom, MD
PSU Research, Department of Medicine
Participant flow
Recruitment details
The study was conducted at a single site.
Pre-assignment details
In the double-blind period, participants were randomly assigned to receive MN-001 or placebo in a 2:1 ratio, meaning that 10 participants received MN-001 and 5 participants received placebo. In the Open-label period, all 15 participants who completed the double-blind period received MN-001.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 66.2 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 | 0 / 15 |
| other Total, other adverse events | 10 / 10 | 5 / 5 | 15 / 15 |
| serious Total, serious adverse events | 1 / 10 | 3 / 5 | 3 / 15 |
Outcome results
None listed