Clinical trial NCT02550873: A Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-16
Enrollment: 117
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: 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.

Eligibility criteria: 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%.

Primary outcomes:
measure: Change From Baseline in Forced Vital Capacity (FVC) [% Predicted]
timeFrame: 0 to 28 weeks
Secondary outcomes:
measure: Change From Baseline in 6-Minute Walk Distance (6MWD)
timeFrame: 0 to 28 weeks
measure: Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT)
timeFrame: 0 to 28 weeks
measure: Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT
timeFrame: 0 to 28 weeks
measure: Change From Baseline in % of Total Lung Volume of ILA on HRCT
timeFrame: 0 to 28 weeks
measure: Change From Baseline in Volume of Normal Lung on HRCT
timeFrame: 0 to 28 weeks
measure: Change From Baseline in % of Normal Lung on HRCT (%)
timeFrame: 0 to 28 weeks
measure: Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA
timeFrame: 0 to 28 weeks
measure: Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28.
timeFrame: 0 to 28 weeks
measure: Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28.
timeFrame: 0 to 28 weeks
measure: Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28.
timeFrame: 0 to 28 weeks
measure: Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28
timeFrame: 0 to 28 weeks
measure: Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28.
timeFrame: 0 to 28 weeks
measure: Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28.
timeFrame: 0 to 28 weeks
measure: Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO).
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects Discontinuing Study Drug Due to AEs
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects Reporting Respiratory Decline AEs
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability]
timeFrame: 0 to 28 weeks
measure: Percentage of Subjects With Infusion Related Reactions
timeFrame: 0 to 28 weeks
measure: All Cause Mortality
timeFrame: 0 to 28 weeks
measure: Mortality Due to Respiratory Deterioration
timeFrame: 0 to 28 weeks
measure: Mortality Due to Disease Related Events
timeFrame: 0 to 28 weeks
Other outcomes:
measure: Change From Baseline in FVC Volume
timeFrame: 0 to 28 weeks
Locations:
city: San Francisco
country: United States
facility: UCSF Interstitial Lung Disease Program
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Dallas
country: United States
facility: UT - Southwestern Medical School
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Prague
country: Czechia
facility: Thomayer Hospital
city: Giessen
country: Germany
facility: Justus-Liebig University Giessen
city: Heidelberg
country: Germany
facility: Thoraxklinik University of Heidelberg
city: Catania
country: Italy
facility: Az. Ospedaliera Universitaria-Policlinico V. Emanuele di Catania
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid Holland
city: Barcelona
country: Spain
facility: Hospital University de Bellvitge
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
Study officials:
affiliation: Hoffmann-La Roche
name: Bernt van den Blink, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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 on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial. JAMA. 2018 Jun 12;319(22):2299-2307. doi: 10.1001/jama.2018.6129.
citation: Raghu G, Hamblin MJ, Brown AW, Golden JA, Ho LA, Wijsenbeek MS, Vasakova M, Pesci A, Antin-Ozerkis DE, Meyer KC, Kreuter M, Burgess T, Kamath N, Donaldson F, Richeldi L. Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 (rhPTX-2) in patients with idiopathic pulmonary fibrosis (IPF): an open-label extension study. Respir Res. 2022 May 21;23(1):129. doi: 10.1186/s12931-022-02047-0.
citation: 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, Moran D, Santin-Janin H, Aubin F, Mulder GJ, Gupta R, Richeldi L. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med. 2019 Aug;7(8):657-664. doi: 10.1016/S2213-2600(19)30172-9. Epub 2019 May 20.