A Phase 1b Study of IV PRM151 in Patients With Idiopathic Pulmonary Fibrosis (IPF) (PRM151F-12GL)

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

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.

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.

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.

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.

Number of subjects with Dose Limiting Toxicities, Number of Treatment Emergent Serious Adverse Events and Adverse Events

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.

Change from baseline (measured during screening period) in distance walked during a 6 minute walk test

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.

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).

van den Blink B, Dillingh MR, Ginns LC, Morrison LD, Moerland M, Wijsenbeek M, Trehu EG, Bartholmai BJ, Burggraaf J. Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy. Eur Respir J. 2016 Mar;47(3):889-97. doi: 10.1183/13993003.00850-2015. Epub 2016 Feb 11.