A Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Phase 2

Completed

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

• Registration Number: NCT02550873
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This study is a Phase 2, randomized, double-blind, placebo controlled, pilot study designed to evaluate the efficacy and safety of PRM-151 administered through Week 24 to subjects with IPF.

Detailed Description

PRM-151 is an anti-fibrotic immunomodulator being developed for treatment of fibrotic diseases.

Study Timeline

• Study First Submitted: 2015-08-27
• Study Start: 2015-09-01
• Study First Submitted QC: 2015-09-14
• Study First Posted: 2015-09-16
• Primary Completion: 2017-05-02
• Study Completion: 2017-05-02
• Results First Submitted: 2018-11-20
• Results First Submitted QC: 2018-11-20
• Results First Posted: 2018-12-14
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-31
• Last Update Posted: 2022-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Has emphysema ≥ 50% on HRCT or the extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT.

2. Has a history of cigarette smoking within the previous 3 months.

3. Has received investigational therapy for IPF within 4 weeks before baseline.

4. Is receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks of baseline.

5. Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline.

6. Has a history of a malignancy within the previous 5 years, with the exception of basal cell skin neoplasms. In addition, a malignant diagnosis or condition first occurring prior to 5 years must be considered cured, inactive, and not under current treatment.

7. Has any concurrent condition other than IPF that, in the Investigator's opinion, is unstable and/or would impact the likelihood of survival for the study duration or the subject's ability to complete the study as designed, or may influence any of the safety or efficacy assessments included in the study.

8. Has baseline resting oxygen saturation of < 89% on room air or supplemental oxygen.

9. Is unable to refrain from use of the following:

   • Short acting bronchodilators on the day of and within 12 hours of pulmonary function, DLCO, and 6 minute walk assessments.
   • Long acting bronchodilators on the day of and within 24 hours of these assessments.

10. Has a known post bronchodilator (short acting beta agonist [SABA] - albuterol or salbutamol) increase in FEV1 of >10% and in FVC of >7.5%.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Dosing Every 4 weeks
PRM-151 10mg / kg	PRM-151	Dosing Every 4 Weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Forced Vital Capacity (FVC) [% Predicted]	0 to 28 weeks	Determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC% predicted, pooling subjects on a stable dose of pirfenidone or nintedanib with subjects not on other treatment for IPF.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT)	0 to 28 weeks	Mean change from baseline in total lung volume on HRCT using quantitative imaging software.
Change From Baseline in Volume of Normal Lung on HRCT	0 to 28 weeks	Mean change from baseline in volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28.	0 to 28 weeks	Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC% predicted of ≥ 5% and ≥ 10% from Baseline to Week 28.
Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28	0 to 28 weeks
Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT	0 to 28 weeks	Mean change from baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software
Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA	0 to 28 weeks	Correlation between mean change from Baseline in FVC \[% predicted\] and mean change from Baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing by quantitative imaging software.
Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28.	0 to 28 weeks
Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO).	0 to 28 weeks	Pulmonary Function Tests to discern the mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO).
Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability]	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs
All Cause Mortality	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality
Mortality Due to Respiratory Deterioration	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration
Change From Baseline in 6-Minute Walk Distance (6MWD)	0 to 28 weeks
Percentage of Subjects Reporting Serious Adverse Events (SAEs)	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by incidence of SAEs
Percentage of Subjects With Infusion Related Reactions	0 to 28 weeks	Infusion Related Reactions were defined as events of headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, hypotension, lightheadedness, palpitations, urticaria and somnolence occurring between the start of a study treatment infusion and one hour after completion of the infusion.
Mortality Due to Disease Related Events	0 to 28 weeks	Number of patients who died over the 28 week study period due to disease-related events (defined as cough, IPF exacerbation, IPF progression and respiratory decline AEs)
Change From Baseline in % of Total Lung Volume of ILA on HRCT	0 to 28 weeks	Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software
Change From Baseline in % of Normal Lung on HRCT (%)	0 to 28 weeks	Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28.	0 to 28 weeks
Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28.	0 to 28 weeks
Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28.	0 to 28 weeks
Percentage of Subjects Discontinuing Study Drug Due to AEs	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the proportion of subjects who discontinued study drug due to AEs
Percentage of Subjects Reporting Respiratory Decline AEs	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the number of reported respiratory decline AEs, defined as follows: * Unscheduled visits to a healthcare professional for respiratory status deterioration.; * Urgent care visits for respiratory status deterioration.; * Hospitalization due to a worsening or exacerbation of respiratory symptoms.
Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs)	0 to 28 weeks	Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs

Trial Locations

Locations (18)

Justus-Liebig University Giessen; 🇩🇪 Giessen, Germany

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

UT - Southwestern Medical School; 🇺🇸 Dallas, Texas, United States

Az. Ospedaliera Universitaria-Policlinico V. Emanuele di Catania; 🇮🇹 Catania, Italy

Erasmus Medical Center; 🇳🇱 Rotterdam, Zuid Holland, Netherlands

Centre Hospitalier Universitaire Vaudois (CHUV); 🇨🇭 Lausanne, Switzerland

UCSF Interstitial Lung Disease Program; 🇺🇸 San Francisco, California, United States

National Jewish Medical and Research Center; 🇺🇸 Denver, Colorado, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

University of Wisconsin-Madison; 🇺🇸 Madison, Wisconsin, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

Thomayer Hospital; 🇨🇿 Prague, Czechia

Thoraxklinik University of Heidelberg; 🇩🇪 Heidelberg, Germany

Azienda Ospedaliera San Gerardo; 🇮🇹 Monza, Italy

Hospital University de Bellvitge; 🇪🇸 Barcelona, Spain

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

University of Louisville Hospital; 🇺🇸 Louisville, Kentucky, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States