A Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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This study is a Phase 2, randomized, double-blind, placebo controlled, pilot study designed to evaluate the efficacy and safety of PRM-151 administered through Week 24 to subjects with IPF.

Detailed Description
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PRM-151 is an anti-fibrotic immunomodulator being developed for treatment of fibrotic diseases.

Official Title
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A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Biological: PRM-151
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Is aged 40-80 years. Has IPF satisfying the American Thoracic Society/European Respiratory Society /Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) diagnostic criteria (Raghu, Collard et al. 2011). In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must be consistent with usual interstitial pneumonia (UIP) defined as meeting either criteria A, B, and C, or criteria A and C, or criteria B and C below: Definite honeycomb lung destruction with basal and peripheral predominance. Presence of reticular abnormality AND traction bronchiectasis consistent with fibrosis, with basal and peripheral predominance. Atypical features are absent, specifically nodules and consolidation. Ground glass opacity, if present, is less extensive than reticular opacity pattern. If on pirfenidone or nintedanib, subject must have been on a stable dose of pirfenidone or nintedanib for at least 3 months without increase in forced vital capacity (FVC)% predicted on two consecutive pulmonary function tests (PFTs), including screening PFTs. Subjects may not be on both pirfenidone and nintedanib. If not currently receiving pirfenidone or nintedanib, subject must have been off pirfenidone or nintedanib for ≥ 4 weeks before baseline. Has a FVC ≥ 50% and ≤ 90% of predicted. Has a DLCO ≥ 25% and ≤ 90% of predicted. Minimum distance on 6-Minute Walk Test (6MWT) of 150 meters. Has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70. Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤ 55 years or 12 months if > 55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are defined in the protocol. Has a life expectancy of at least 9 months According to the investigator's best judgment, can comply with the requirements of the protocol. Has provided written informed consent to participate in the study. Exclusion Criteria: Has emphysema ≥ 50% on HRCT or the extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT. Has a history of cigarette smoking within the previous 3 months. Has received investigational therapy for IPF within 4 weeks before baseline. Is receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks of baseline. Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline. Has a history of a malignancy within the previous 5 years, with the exception of basal cell skin neoplasms. In addition, a malignant diagnosis or condition first occurring prior to 5 years must be considered cured, inactive, and not under current treatment. Has any concurrent condition other than IPF that, in the Investigator's opinion, is unstable and/or would impact the likelihood of survival for the study duration or the subject's ability to complete the study as designed, or may influence any of the safety or efficacy assessments included in the study. Has baseline resting oxygen saturation of < 89% on room air or supplemental oxygen. Is unable to refrain from use of the following: Short acting bronchodilators on the day of and within 12 hours of pulmonary function, DLCO, and 6 minute walk assessments. Long acting bronchodilators on the day of and within 24 hours of these assessments. Has a known post bronchodilator (short acting beta agonist [SABA] - albuterol or salbutamol) increase in FEV1 of >10% and in FVC of >7.5%.

Ages Eligible for Study
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Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRM-151 10mg / kg<br>Dosing Every 4 Weeks | Biological: PRM-151<br>* PRM 151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks<br>|
| Placebo Comparator: Placebo<br>Dosing Every 4 weeks | Other: placebo<br>* Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Vital Capacity (FVC) [% Predicted] | Determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC% predicted, pooling subjects on a stable dose of pirfenidone or nintedanib with subjects not on other treatment for IPF. | 0 to 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 6-Minute Walk Distance (6MWD) |  | 0 to 28 weeks | 
| Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | Mean change from baseline in total lung volume on HRCT using quantitative imaging software. | 0 to 28 weeks | 
| Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | Mean change from baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software | 0 to 28 weeks | 
| Change From Baseline in % of Total Lung Volume of ILA on HRCT | Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software | 0 to 28 weeks | 
| Change From Baseline in Volume of Normal Lung on HRCT | Mean change from baseline in volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software. | 0 to 28 weeks | 
| Change From Baseline in % of Normal Lung on HRCT (%) | Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software. | 0 to 28 weeks | 
| Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA | Correlation between mean change from Baseline in FVC [% predicted] and mean change from Baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing by quantitative imaging software. | 0 to 28 weeks | 
| Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC% predicted of ≥ 5% and ≥ 10% from Baseline to Week 28. | 0 to 28 weeks | 
| Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. |  | 0 to 28 weeks | 
| Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. |  | 0 to 28 weeks | 
| Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 |  | 0 to 28 weeks | 
| Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. |  | 0 to 28 weeks | 
| Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. |  | 0 to 28 weeks | 
| Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | Pulmonary Function Tests to discern the mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO). | 0 to 28 weeks | 
| Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) | Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs | 0 to 28 weeks | 
| Percentage of Subjects Discontinuing Study Drug Due to AEs | Tolerability/safety was assessed over the 28-week study period by the proportion of subjects who discontinued study drug due to AEs | 0 to 28 weeks | 
| Percentage of Subjects Reporting Serious Adverse Events (SAEs) | Tolerability/safety was assessed over the 28-week study period by incidence of SAEs | 0 to 28 weeks | 
| Percentage of Subjects Reporting Respiratory Decline AEs | Tolerability/safety was assessed over the 28-week study period by the number of reported respiratory decline AEs, defined as follows: Unscheduled visits to a healthcare professional for respiratory status deterioration. Urgent care visits for respiratory status deterioration. Hospitalization due to a worsening or exacerbation of respiratory symptoms. | 0 to 28 weeks | 
| Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability] | Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs | 0 to 28 weeks | 
| Percentage of Subjects With Infusion Related Reactions | Infusion Related Reactions were defined as events of headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, hypotension, lightheadedness, palpitations, urticaria and somnolence occurring between the start of a study treatment infusion and one hour after completion of the infusion. | 0 to 28 weeks | 
| All Cause Mortality | Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality | 0 to 28 weeks | 
| Mortality Due to Respiratory Deterioration | Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration | 0 to 28 weeks | 
| Mortality Due to Disease Related Events | Number of patients who died over the 28 week study period due to disease-related events (defined as cough, IPF exacerbation, IPF progression and respiratory decline AEs) | 0 to 28 weeks |