cryptogenic fibrosing alveolitis
Conditions
Interventions
Patients randomized to study drug will receive IV infusions of 10 mg/kg PRM-151
over approximately 50 to 70 minutes, with dose based on the patient*s weight
taken at the same clinic visit (for loadi
Sponsors
Hoffmann-La Roche
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Signed Informed Consent Form * Age 40-85 years, inclusive, at time of signing Informed Consent Form * Ability to comply with the requirements of the study protocol, according to the investigator*s best judgment * Documented diagnosis of IPF per the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline * HRCT pattern consistent with the diagnosis of IPF, confirmed by central review of Chest HRCT (available HRCT of acceptable quality performed within 12 months prior to screening or obtained during the screening period) 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 (* 5000 feet [1524 meters] above sea level) 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 * 90% of predicted during screening (Hgb corrected or uncorrected) as determined by the over-reader * If receiving pirfenidone or nintedanib treatment for IPF, the patient must have been on treatment for at least 3 months and on a stable dose for at least 4 weeks prior to screening, and during screening (with no contraindications according to local prescribing information) * If not currently receiving nintedanib or pirfenidone treatment (either treatment naïve or having previously taken and discontinued) must have discontinued such treatment * 4 weeks prior to screening and during screening If patient is considering starting treatment with either nintedanib or pirfenidone, patient must be on treatment for at least 3 months prior to screening, provided there are no contraindications according to local prescribing information. * For women of childbearing potential: (excluding patients enrolling in Japan): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of * 1% per year during the treatment period and for 8 weeks after the final dose of PRM-151. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of * 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation met
Exclusion criteria
Exclusion criteria: * Evidence of other known causes of interstitial lung disease (e.g., domestic and occupational environmental exposures, connective-tissue disease, and drug toxicity) * 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, immunosuppressive, cytokine modulating, or receptor antagonist agents (including but not limited to methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine or other steroid sparing agent) 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 * Positive interferon gamma release assay - Test for tuberculosis during screening: Patients who have completed treatment for tuberculosis within 6 months prior to screening, and have no evidence of recurrent disease, do not need to be tested * Resting oxygen saturation of * 89% using up to 4 L/min of supplemental oxygen at sea level and up-to 6 L/min at altitude (* 5000 feet [1524 meters] above sea level) during screening * Co-existing acute or chronic medical condition that, in the investigator*s opinion, would substantially limit the ability to comply with study requirements or may influence any of the safety or efficacy assessments included in the study * Class IV New York Heart Association chronic heart failure PRM-151*F. Hoffmann-La Roche Ltd 24/Protocol WA42293, Version 2 (VHP) * Historical evidence of left ventricular ejection fraction * 35% * Presence of pulmonary hypertension that, in the investigator*s opinion, would substantially limit the ability to comply with study requirements or may influence any of the safety or efficacy assessments included in the study * Cardiopulmonary rehabilitation program based on exercise training that has been completed within 8 weeks prior to screening or planned to start during the patient*s enrollment in this trial * History of smoking (including cigarette, cannabis, cigar, pipe and vaping) within 3 months prior to or during screening * History of alcohol or substance use disorder within 2 years prior to or during screening or known or suspected active alcohol or substance-use disorder * History of a malignancy within the 5 years prior to screening, with the exception of basal cell or squamous cell skin neoplasms. In addition, a malignant diagnosis or condition that occurred more than 5 years prior to screening, and any basal cell or squamous cell neoplasm must be considered cured, inactive, and not under treatment. * Unable to refrain from use of the following: - Short acting bronchodilators (SABA) within 4 hours before pulmo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy objective is to demonstrate superiority of 10 mg/kg PRM-151 plus standard of care treatment as needed (excluding lung transplantation) administered Q4W via IV infusion, over matching placebo plus standard of care treatment as needed (excluding lung transplantation), on lung function on the basis of absolute change in baseline to week 52 in forced vital capacity (FVC (mL)) | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy objective is to demonstrate superiority of 10 mg/kg PRM-151 plus standard of care treatment as needed (excluding lung transplantation) administered Q4W via IV infusion, over matching placebo plus standard of care treatment as needed (excluding lung transplantation) on the basis of the following endpoints: * Absolute change from baseline to Week 52 in 6MWD (in meters) * Absolute change from baseline to Week 52 in FVC% predicted * Time to disease progression, defined as time to first occurrence of >= 10% absolute decline in % predicted FVC, >= 15% relative decline in 6MWD, or death * Time to first respiratory-related hospitalizations (defined as non-elective hospitalizations due to any respiratory cause, including acute exacerbations of IPF, or suspected acute exacerbations of IPF, as determined by the clinical Adjudication Committee) * 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, as determined by clinical Adjudication Committee * Change from baseline to Week 52 in carbon monoxide diffusing capacity (DLCO) * Survival, as measured by all-cause mortality The exploratory efficacy objective for this study is to evaluate the efficacy of PRM-151 plus standard of care treatment as needed (excluding lung transplantation) compared with matching placebo plus standard of care treatment as needed (excluding lung transplantation) on the basis of the following endpoints: * Change from baseline to Week 52 in FVC% predicted, FVC (mL), by concurrent therapy stratum (i.e., with nintedanib treatment vs. with pirfenidone treatment vs. without pirfenidone or nintedanib treatment) * Change from baseline to Week 52 in FVC% predicted, FVC (mL), by MUC5B risk allele positive or negative st | — |
Countries
Netherlands
Outcome results
None listed