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

Phase 1

Completed

• Conditions: Idiopathic Pulmonary Fibrosis
• Interventions: Biological: PRM-151; Other: Placebo

• Registration Number: NCT01254409
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-12-03
• Study First Submitted QC: 2010-12-03
• Study First Posted: 2010-12-06
• Study Start: 2011-03-29
• Primary Completion: 2012-07-02
• Study Completion: 2012-07-02
• Results First Submitted: 2014-04-11
• Results First Submitted QC: 2014-10-24
• Results First Posted: 2014-11-02
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-31
• Last Update Posted: 2022-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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.

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PRM-151	PRM-151	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.
Placebo	Placebo	0.9% saline administered by 30 minute IV infusion Days 1, 3, 5, 8, and 15.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	From first dose on Day 1 through Day 57	Number of subjects with Dose Limiting Toxicities, Number of Treatment Emergent Serious Adverse Events and Adverse Events

Secondary Outcome Measures

Name	Time	Method
Cmax	Day 15	Maximum concentration
Tmax	Day 15	Time of Maximum observed concentration
AUC48	Day 15	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.
Total Body Clearance	Day 15
Terminal Elimination Half Life	Day 15
Vss	Day 15	Volume of Distribution at Steady State
FEV1 (Forced Expiratory Volume 1sec )(%) Change From Baseline	Day 1 (Baseline) and Day 57
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
6MWT (6 Minute Walk Test) Distance Walked Change From Baseline	Screening (between Day -35 and Day 1) and Day 57	Change from baseline (measured during screening period) in distance walked during a 6 minute walk test
SGRQ (St. George's Respiratory Questionnaire) Total Score Change From Baseline	Day 1 (Baseline) and Day 57	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.

Trial Locations

Locations (3)

Duke Clinical Research Unit; 🇺🇸 Durham, North Carolina, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Center for Human Drug Research; 🇳🇱 Leiden, Netherlands