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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02550873
• Other study ID #: WA42404
• Secondary ID: PRM-151-2022014-
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2015
• Est. completion date: May 2, 2017

Study information

• Verified date: March 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: May 2, 2017
• Est. primary completion date: May 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria

1. Is aged 40-80 years.

2. Has IPF satisfying the American Thoracic Society/European Respiratory Society /Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) diagnostic criteria (Raghu, Collard et al. 2011). In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must be "consistent with "usual interstitial pneumonia" (UIP) defined as meeting either criteria A, B, and C, or

criteria A and C, or criteria B and C below:

• Definite honeycomb lung destruction with basal and peripheral predominance.
• Presence of reticular abnormality AND traction bronchiectasis consistent with fibrosis, with basal and peripheral predominance.
• Atypical features are absent, specifically nodules and consolidation. Ground glass opacity, if present, is less extensive than reticular opacity pattern.

3. If on pirfenidone or nintedanib, subject must have been on a stable dose of pirfenidone or nintedanib for at least 3 months without increase in forced vital capacity (FVC)% predicted on two consecutive pulmonary function tests (PFTs), including screening PFTs. Subjects may not be on both pirfenidone and nintedanib.

4. If not currently receiving pirfenidone or nintedanib, subject must have been off pirfenidone or nintedanib for = 4 weeks before baseline.

5. Has a FVC = 50% and = 90% of predicted.

6. Has a DLCO = 25% and = 90% of predicted.

7. Minimum distance on 6-Minute Walk Test (6MWT) of 150 meters.

8. Has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.

9. Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if = 55 years or 12 months if > 55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are defined in the protocol.

10. Has a life expectancy of at least 9 months

11. According to the investigator's best judgment, can comply with the requirements of the protocol.

12. Has provided written informed consent to participate in the study.

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%.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Biological:
• PRM-151
PRM 151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks

Other:
• placebo
Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks

Locations

Country	Name	City	State
Czechia	Thomayer Hospital	Prague
Germany	Justus-Liebig University Giessen	Giessen
Germany	Thoraxklinik University of Heidelberg	Heidelberg
Italy	Az. Ospedaliera Universitaria-Policlinico V. Emanuele di Catania	Catania
Italy	Azienda Ospedaliera San Gerardo	Monza
Netherlands	Erasmus Medical Center	Rotterdam	Zuid Holland
Spain	Hospital University de Bellvitge	Barcelona
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UT - Southwestern Medical School	Dallas	Texas
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Louisville Hospital	Louisville	Kentucky
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	UCSF Interstitial Lung Disease Program	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Italy,  Netherlands,  Spain,  Switzerland, 

References & Publications (1)

Raghu G, van den Blink B, Hamblin MJ, Brown AW, Golden JA, Ho LA, Wijsenbeek MS, Vasakova M, Pesci A, Antin-Ozerkis DE, Meyer KC, Kreuter M, Santin-Janin H, Mulder GJ, Bartholmai B, Gupta R, Richeldi L. Effect of Recombinant Human Pentraxin 2 vs Placebo o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in FVC Volume		0 to 28 weeks
Primary	Change From Baseline in Forced Vital Capacity (FVC) [% Predicted]	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.	0 to 28 weeks
Secondary	Change From Baseline in 6-Minute Walk Distance (6MWD)		0 to 28 weeks
Secondary	Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT)	Mean change from baseline in total lung volume on HRCT using quantitative imaging software.	0 to 28 weeks
Secondary	Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT	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	0 to 28 weeks
Secondary	Change From Baseline in % of Total Lung Volume of ILA on HRCT	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	0 to 28 weeks
Secondary	Change From Baseline in Volume of Normal Lung on HRCT	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.	0 to 28 weeks
Secondary	Change From Baseline in % of Normal Lung on HRCT (%)	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.	0 to 28 weeks
Secondary	Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA	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.	0 to 28 weeks
Secondary	Number of Subjects With a Decline in FVC [% Predicted] of = 5% and = 10% From Baseline to Week 28.	Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC% predicted of = 5% and = 10% from Baseline to Week 28.	0 to 28 weeks
Secondary	Number of Subjects With a Decline in FVC of = 100 mL and = 200 mL From Baseline to Week 28.		0 to 28 weeks
Secondary	Number of Subjects With an Increase in FVC [% Predicted] of = 5% and =10% From Baseline to Week 28.		0 to 28 weeks
Secondary	Number of Subjects With an Increase in FVC of = 100 mL and = 200 mL From Baseline to Week 28		0 to 28 weeks
Secondary	Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28.		0 to 28 weeks
Secondary	Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28.		0 to 28 weeks
Secondary	Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO).	Pulmonary Function Tests to discern the mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO).	0 to 28 weeks
Secondary	Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs)	Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs	0 to 28 weeks
Secondary	Percentage of Subjects Discontinuing Study Drug Due to AEs	Tolerability/safety was assessed over the 28-week study period by the proportion of subjects who discontinued study drug due to AEs	0 to 28 weeks
Secondary	Percentage of Subjects Reporting Serious Adverse Events (SAEs)	Tolerability/safety was assessed over the 28-week study period by incidence of SAEs	0 to 28 weeks
Secondary	Percentage of Subjects Reporting Respiratory Decline AEs	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.	0 to 28 weeks
Secondary	Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability]	Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs	0 to 28 weeks
Secondary	Percentage of Subjects With Infusion Related Reactions	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.	0 to 28 weeks
Secondary	All Cause Mortality	Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality	0 to 28 weeks
Secondary	Mortality Due to Respiratory Deterioration	Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration	0 to 28 weeks
Secondary	Mortality Due to Disease Related Events	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)	0 to 28 weeks