Clinical trial NCT01254409: A Phase 1b Study of IV PRM151 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: pulmonary, fibrosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-12-06
Enrollment: 21
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Safety and Tolerability
timeFrame: From first dose on Day 1 through Day 57
Secondary outcomes:
measure: Cmax
timeFrame: Day 15
measure: Tmax
timeFrame: Day 15
measure: AUC48
timeFrame: Day 15
measure: Terminal Elimination Half Life
timeFrame: Day 15
measure: Total Body Clearance
timeFrame: Day 15
measure: Vss
timeFrame: Day 15
measure: FVC (Forced Vital Capacity) Change From Baseline to Day 57
timeFrame: Change from Day 1 (Baseline) to Day 57
measure: FVC (Forced Vital Capacity) % Predicted Change From Baseline
timeFrame: Day 1 (Baseline) and Day 57
measure: DLCO (%) (Diffusing Capacity of Carbon Monoxide) Change From Baseline
timeFrame: Day 1 (Baseline) and Day 57
measure: FEV1 (Forced Expiratory Volume 1sec )(%) Change From Baseline
timeFrame: Day 1 (Baseline) and Day 57
measure: 6MWT (6 Minute Walk Test) Distance Walked Change From Baseline
timeFrame: Screening (between Day -35 and Day 1) and Day 57
measure: SGRQ (St. George's Respiratory Questionnaire) Total Score Change From Baseline
timeFrame: Day 1 (Baseline) and Day 57
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke Clinical Research Unit
state: North Carolina
city: Leiden
country: Netherlands
facility: Center for Human Drug Research
Study officials:
affiliation: Hoffmann-La Roche
name: John Getsy, DMD, DO
role: STUDY_DIRECTOR
References:
citation: 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.