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

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ClinicalTrials.gov Identifier: NCT02550873
Recruitment Status : Completed
First Posted : September 16, 2015
Results First Posted : December 14, 2018
Last Update Posted : March 24, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE August 27, 2015
First Posted Date  ICMJE September 16, 2015
Results First Submitted Date  ICMJE November 20, 2018
Results First Posted Date  ICMJE December 14, 2018
Last Update Posted Date March 24, 2021
Actual Study Start Date  ICMJE September 7, 2015
Actual Primary Completion Date May 2, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
Forced vital capacity (FVC)% predicted change from baseline [ Time Frame: 0 to 28 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • Change From Baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: 0 to 28 weeks ]
  • 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.
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ]
  • Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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).
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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.
  • 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
  • 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
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
  • Mean change from baseline in volume of interstitial lung abnormalities (ILA) on high-resolution computed tomography (HRCT) (ml) [ 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
  • Mean change from baseline in % of total lung volume of interstitial lung abnormalities (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
  • Mean change from Baseline in volume of normal lung on HRCT (ml) [ Time Frame: 0 to 28 weeks ]
  • Mean change from Baseline in % of total lung volume of normal lung on HRCT (%) [ Time Frame: 0 to 28 weeks ]
  • Correlation between mean change from Baseline in FVC % predicted and mean change from Baseline in interstitial lung abnormalities (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 interstitial lung abnormalities (ILA), including ground glass density, reticular changes, and honeycombing by quantitative imaging software.
  • Incidence of adverse events (AEs) [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Incidence of serious adverse events (SAEs) [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Incidence of respiratory AEs [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Incidence of respiratory SAEs [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Proportion of subjects discontinuing study drug due to AEs [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • All cause mortality rate [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Mortality rate due to respiratory deterioration [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
  • Incidence of disease related events associated with mortality [Safety and Tolerability] [ Time Frame: 0 to 28 weeks ]
    Description: Number of "respiratory decline" events over the 28 week study period as defined below:
    • Unscheduled visits to a healthcare professional for respiratory status deterioration.
    • Urgent care visit for respiratory status deterioration.
    • Hospitalization due to a worsening or exacerbation of respiratory symptoms.
    • Acute onset of symptoms (< 30 days in duration)
    • New radiographic abnormalities (bilateral ground glass or consolidation on HRCT with no pneumothorax or pleural effusion)
    • Absence of an identified infectious etiology by routine clinical practice
    • Exclusion of alternative causes by routine clinical practice, including:
      • Left heart failure
      • Pulmonary embolism
      • Identifiable cause of acute lung injury
  • Proportion (%) of subjects with a decline in FVC% predicted of ≥ 5% and ≥ 10% from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • Proportion (%) of subjects with a decline in FVC of ≥ 100ml and ≥ 200ml from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • Proportion of subjects with an increase in FVC % predicted of ≥ 5% and ≥10% from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • Proportion of subjects with an increase in FVC of ≥ 100 ml and ≥ 200 ml from Baseline to Week 28 [ Time Frame: 0 to 28 weeks ]
  • Proportion of subjects with stable disease by FVC %, defined as a change in FVC % predicted of < 5% from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • Proportion of subjects with stable disease by FVC in ml, defined as a change in FVC of < 100ml from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
  • Mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO). [ Time Frame: 0 to 28 weeks ]
  • Change in 6-minute walk distance, in meters, from Baseline to Week 28. [ Time Frame: 0 to 28 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: November 20, 2018)
Change From Baseline in FVC Volume [ Time Frame: 0 to 28 weeks ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Official Title  ICMJE A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Pulmonary Fibrosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: PRM-151 10mg / kg
    Dosing Every 4 Weeks
    Intervention: Biological: PRM-151
  • Placebo Comparator: Placebo
    Dosing Every 4 weeks
    Intervention: Other: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 14, 2015)
117
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2, 2017
Actual Primary Completion Date May 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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%.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Germany,   Italy,   Netherlands,   Spain,   Switzerland,   United States
Removed Location Countries Belgium,   Czech Republic,   Israel,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02550873
Other Study ID Numbers  ICMJE WA42404
PRM-151-202 ( Other Identifier: Promedior, Inc. )
2014-004782-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bernt van den Blink, MD, PhD Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP