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

• ClinicalTrials.gov Identifier: NCT02550873
• Recruitment Status: Completed
• First Posted: September 16, 2015
• Results First Posted: December 14, 2018
• Last Update Posted: May 2, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Biological: PRM-151; Other: placebo	Phase 2

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Actual Study Start Date: September 1, 2015
• Actual Primary Completion Date: May 2, 2017
• Actual Study Completion Date: May 2, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: PRM-151 10mg / kg; Dosing Every 4 Weeks	Biological: PRM-151; PRM 151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks
Placebo Comparator: Placebo; Dosing Every 4 weeks	Other: placebo; Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Forced Vital Capacity (FVC) [% Predicted] [ Time Frame: 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 :

1. Change From Baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: 0 to 28 weeks ]
2. Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) [ Time Frame: 0 to 28 weeks ]
   Mean change from baseline in total lung volume on HRCT using quantitative imaging software.
3. Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT [ Time Frame: 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
4. Change From Baseline in % of Total Lung Volume of ILA on HRCT [ Time Frame: 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
5. Change From Baseline in Volume of Normal Lung on HRCT [ Time Frame: 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.
6. Change From Baseline in % of Normal Lung on HRCT (%) [ Time Frame: 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.
7. Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA [ Time Frame: 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.
8. Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. [ Time Frame: 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.
9. Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
10. Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
11. Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 [ Time Frame: 0 to 28 weeks ]
12. Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
13. Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
14. Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). [ Time Frame: 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).
15. Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 0 to 28 weeks ]
    Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs
16. Percentage of Subjects Discontinuing Study Drug Due to AEs [ Time Frame: 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
17. Percentage of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: 0 to 28 weeks ]
    Tolerability/safety was assessed over the 28-week study period by incidence of SAEs
18. Percentage of Subjects Reporting Respiratory Decline AEs [ Time Frame: 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.
19. Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
    Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs
20. Percentage of Subjects With Infusion Related Reactions [ Time Frame: 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.
21. All Cause Mortality [ Time Frame: 0 to 28 weeks ]
    Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality
22. Mortality Due to Respiratory Deterioration [ Time Frame: 0 to 28 weeks ]
    Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration
23. Mortality Due to Disease Related Events [ Time Frame: 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)

Other Outcome Measures:

1. Change From Baseline in FVC Volume [ Time Frame: 0 to 28 weeks ]

Eligibility Criteria

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

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%.

Contacts and Locations

Locations

United States, California

UCSF Interstitial Lung Disease Program

San Francisco, California, United States, 94143

United States, Colorado

National Jewish Medical and Research Center

Denver, Colorado, United States, 80206

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Kentucky

University of Louisville Hospital

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Texas

UT - Southwestern Medical School

Dallas, Texas, United States, 75930

United States, Virginia

Inova Fairfax Hospital

Falls Church, Virginia, United States, 22042

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98195

United States, Wisconsin

University of Wisconsin-Madison

Madison, Wisconsin, United States, 53715

Czechia

Thomayer Hospital

Prague, Czechia, 14059

Germany

Justus-Liebig University Giessen

Giessen, Germany, D-35392

Thoraxklinik University of Heidelberg

Heidelberg, Germany, D-69126

Italy

Az. Ospedaliera Universitaria-Policlinico V. Emanuele di Catania

Catania, Italy, 78-95123

Azienda Ospedaliera San Gerardo

Monza, Italy, 20900

Netherlands

Erasmus Medical Center

Rotterdam, Zuid Holland, Netherlands, 3015 CE

Spain

Hospital University de Bellvitge

Barcelona, Spain, 08907

Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland, CH-1011

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Bernt van den Blink, MD, PhD; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol  [PDF] February 3, 2016

Statistical Analysis Plan  [PDF] June 8, 2017

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02550873
• Other Study ID Numbers: WA42404; PRM-151-202 ( Other Identifier: Promedior, Inc. ); 2014-004782-24 ( EudraCT Number )
• First Posted: September 16, 2015
• Results First Posted: December 14, 2018
• Last Update Posted: May 2, 2022
• Last Verified: March 2022

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases