A Phase 1b Study of IV PRM151 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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The aims of the study are to assess safety, tolerability, the pharmacokinetic profile, and the pharmacodynamic profile of multiple doses of PRM-151 administered IV to IPF patients.

Detailed Description
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Idiopathic pulmonary fibrosis (IPF) is a diffuse lung disease with a histological picture of usual interstitial pneumonia and a deteriorating clinical course. The prognosis is poor. Chronic alveolar inflammation with associated parenchymal remodeling is theorized to promote an ongoing abnormal fibrogenic repair response. Corticosteroids and immunomodulatory agents have not been shown to benefit IPF patients. Recently several published clinical studies have indicated a strong correlation between IPF severity and/or disease progression and the levels of specific plasma biomarker proteins related to epithelial cell health and extracellular matrix turnover. PRM-151 is being developed for potential therapeutic uses to prevent, treat, and reduce fibrosis. This study is the first intravenous multiple-dose study in humans, and will be conducted in patients with IPF. Patients will be randomized to receive either PRM-151 or placebo.

Official Title
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A Randomized, Double-Masked, Sponsor-Unmasked, Ascending Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PRM-151 Administered Intravenously to Patients With Idiopathic Pulmonary Fibrosis

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: Men or women of non-childbearing potential aged 40 to 80 years at screening. Diagnosis of idiopathic pulmonary fibrosis (IPF) as determined by high resolution computerized tomography (HRCT) and pulmonary function tests. Exclusion Criteria: History or presence of connective tissue disorder, tuberculosis (TB), cystic fibrosis, sarcoidosis, amyloidosis or other pulmonary disease except idiopathic pulmonary fibrosis (IPF). History or presence of chronic pulmonary obstructive disease, severe pulmonary hypertension, drug-induced pulmonary toxicity, other forms of idiopathic pneumonia, or interstitial lung diseases associated with environmental exposure medication or systemic disease. High resolution computerized tomography (HRCT) findings inconsistent with idiopathic pulmonary fibrosis(IPF).

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRM-151<br>PRM-151 administered at escalating doses of 1, 5, and 10 mg/kg by 30 minute intravenous (IV) infusion days 1, 3, 5, 8 and 15. | Biological: PRM-151<br>* Intravenous PRM-151 administered over 30 minutes on study days 1, 3, 5, 8, and 15 at doses of 1.0, 5.0, or 10.0 mg/kg.<br>|
| Placebo Comparator: Placebo<br>0.9% saline administered by 30 minute IV infusion Days 1, 3, 5, 8, and 15. | Other: Placebo<br>* Intravenous 0.9% normal saline administered over 30 minutes on study days 1, 3, 5, 8, and 15.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Number of subjects with Dose Limiting Toxicities, Number of Treatment Emergent Serious Adverse Events and Adverse Events | From first dose on Day 1 through Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration | Day 15 | 
| Tmax | Time of Maximum observed concentration | Day 15 | 
| AUC48 | Area under the curve from 0 to 48 hrs post dose, with samples collected at 0.5, 0.75, 1, 1.5, 2, 3,4,6,8,12,16, 24 and 48 hours post Day 15 dose. | Day 15 | 
| Terminal Elimination Half Life |  | Day 15 | 
| Total Body Clearance |  | Day 15 | 
| Vss | Volume of Distribution at Steady State | Day 15 | 
| FVC (Forced Vital Capacity) Change From Baseline to Day 57 |  | Change from Day 1 (Baseline) to Day 57 | 
| FVC (Forced Vital Capacity) % Predicted Change From Baseline |  | Day 1 (Baseline) and Day 57 | 
| DLCO (%) (Diffusing Capacity of Carbon Monoxide) Change From Baseline |  | Day 1 (Baseline) and Day 57 | 
| FEV1 (Forced Expiratory Volume 1sec )(%) Change From Baseline |  | Day 1 (Baseline) and Day 57 | 
| 6MWT (6 Minute Walk Test) Distance Walked Change From Baseline | Change from baseline (measured during screening period) in distance walked during a 6 minute walk test | Screening (between Day -35 and Day 1) and Day 57 | 
| SGRQ (St. George's Respiratory Questionnaire) Total Score Change From Baseline | St. George's Respiratory Questionnaire Total Score. Scores range from 0 (no impairment) to 100 (maximum impairment). A decrease in score represents a decrease in disease related symptoms. The SGRQ is not validated for IPF. | Day 1 (Baseline) and Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary, fibrosis