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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Biological: PRM-151; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Center for Human Drug Research
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: PRM-151; 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.
Placebo Comparator: Placebo; 0.9% saline administered by 30 minute IV infusion Days 1, 3, 5, 8, and 15.	Other: Placebo; Intravenous 0.9% normal saline administered over 30 minutes on study days 1, 3, 5, 8, and 15.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: John Getsy, DMD, DO, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2011
• Primary Completion (Actual): July 2, 2012
• Study Completion (Actual): July 2, 2012

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: pulmonary, fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: WA42403; PRM151F-12GL (Other Identifier: Promedior, Inc.)