Idiopathic pulmonary fibrosis (IPF) MedDRA version: 21.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Recombinant human Pentraxin-2 (PRM-151)
Product Code: RO7490677 160 mg/8mL
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Recombinant human Pentraxin-2
Other descriptive
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 40–85 years • Documented diagnosis of IPF per the 2018 American Thoracic Society / European Respiratory Society / Japanese Respiratory Society / Latin American Thoracic Society Clinical Practice Guideline • High-resolution computed tomography pattern consistent with the diagnosis of IPF, confirmed by central review of Chest HRCT and central review of any available lung biopsy (LB) • Minimum 6MWD of 150 meters with maximum use of 6 L/min at sea-level and up to 8 L/min at altitude of supplemental oxygen while maintaining oxygen saturation of >= 83% during the 6MWT during screening • FVC >= 45% predicted during screening as determined by the over-reader • Forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70 during screening as determined by the over-reader • DLCO >= 30% and = 4 weeks prior to screening and during screening • For women of childbearing potential (excluding patients enrolling in Japan): agreement to remain abstinent or use contraception, women must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 480
Exclusion criteria
Exclusion criteria: • Evidence of other known causes of interstitial lung disease • FVC% predicted value showing improvement in the 6-month period prior to screening and including screening value, as assessed by the investigator Emphysema present on >= 50% of the HRCT, or the extent of emphysema is greater than the extent of fibrosis, according to central review of the HRCT • Receiving nintedanib in combination with pirfenidone • Received cytotoxic, immunosupressive, cytokine modulating, or receptor antagonist agents within 4 weeks prior to or during screening • Receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks prior to or during screening • Receiving strong inhibitor or inducer of CYP1A2 in patients taking pirfenidone • Receiving potent inhibitor or inducer of P-gp in patients taking nintedanib • Acute respiratory or systemic bacterial, viral, or fungal infection either during screening or prior to screening and not successfully resolved 4 weeks prior to screening visit • Patients with active or latent tuberculosis (confirmed within the 6 months prior to or during screening, by a positive screening test [Positive interferon gamma release assay test for tuberculosis during screening]) • Patients who have completed treatment for active or latent tuberculosis within 6 months prior to screening, and have no evidence of recurrent disease, do not need to be tested • Resting oxygen saturation of = 12% and >= 200 mL, respectively • Receipt of an investigational drug within 4 weeks, or 5 half-lives, whichever is longer, prior to or during screening • Previous treatment with PRM-151 • Clinically significant abnormality on ECG during screening that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient • Pregnant or breastfeeding, or intending to become pregnant during the study or within 8 weeks after the final dose of PRM-151
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority of 10 mg/kg PRM-151 + standard of care (SOC) treatment as needed administered every 4 weeks (Q4W) via intravenous (IV) infusion, over matching placebo + SOC treatment as needed, on lung function on the basis of absolute change from baseline to Week 52 in forced vital capacity (FVC);Secondary Objective: To evaluate: • Superiority of 10 mg/kg PRM-151 + SOC treatment as needed administered Q4W via IV infusion, over matching placebo + SOC, on lung function on the basis of absolute change from baseline to Week 52 in 6-minute walk distance (6MWD) (in meters), FVC, time to disease progression, time to first respiratory-related hospitalizations, change from baseline to Week 52 in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ), change from baseline to Week 52 in St. George Respiratory Questionnaire (SGRQ) total score, time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF, change from baseline to Week 52 in carbon monoxide diffusing capacity (DLCO)and survival • Safety, tolerability of 10 mg/kg of PRM-151 administered Q4W via IV infusion + SOC as needed relative to matching placebo + SOC as needed in a population of all dosed patients • Pharmacokinetics of PRM-151 in patients with IPF • Immune response to PRM-151;Primary end point(s): 1. Absolute change from baseline to Week 52 in FVC [mL];Timepoint(s) of evaluation of this end point: 1. From baseline (Day 1) to Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Absolute change from baseline to Week 52 in 6MWD (in meters) 2. Absolute change from baseline to Week 52 in FVC% predicted 3. Time to disease progression 4. Time to first respiratory-related hospitalizations 5. Change from baseline to Week 52 in UCSD-SOBQ 6. Change from baseline to Week 52 in SGRQ Total Score 7. Time to first acute exacerbation of IPF, or suspected acute exacerbation of IPF 8. Change from baseline to Week 52 in DLCO 9. Survival, as measured by all-cause mortality 10. Incidence and severity of adverse events, with severity determined according to the 5-point severity scale (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 [NCI CTCAE, v.5.0]) 11. Incidence and severity of IRRs and other adverse events of special interest 12. Proportion of patients permanently discontinuing study treatment due to adverse events 13. Change from baseline in targeted clinical laboratory test results 14. Plasma concentrations of PRM-151 at specified timepoints 15. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study ;Timepoint(s) of evaluation of this end point: 1-2. From baseline to Week 52 3-4. Up to 2.5 years 5-6. From baseline to Week 52 7. Up to 2.5 years 8. From baseline to Week 52 9-12. Up to 2.5 years 13. From baseline to 2.5 years 14. Day 1, 5 and Weeks 4, 12, 24, 36, 48 and 52 or treatment discontinuation visit and Week 56 and unscheduled visits 15. Day 1 and Weeks 4, 12, 24, 36, 48 and 52 or treatment discontinuation visit and Week 56 and unscheduled visits | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed