A PHASE III RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF PRM-151 IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS
- Conditions
- J84 NULL
- Registration Number
- PER-013-21
- Lead Sponsor
- F. HOFFMANN-LA ROCHE LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Without startig enrollment
- Sex
- All
- Target Recruitment
- 0
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 8 weeks after the final dose of PRM-151 to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
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 methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.
• Anticipated life expectancy of at least 12 months at baseline, according to the investigator’s judgment
• Patient and investigator considered all medicinal treatment options and/or possibly lung transplantation prior to considering participation in the study. If the patient is on a lung transplant list, the investigator anticipates the patient will be able to complete the study prior to transplant.
• For patients enrolled in the extended China enrollment phase at NMPA-recognized sites: current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry
• 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 lung biopsy (LB), if available
• 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
• Forced expiratory volume in 1 second (FEV1)/FVC ratio >0.70 during screening
• DLCO =30% and =90% of predicted during screening (Hgb corrected or uncorrected)
• 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
• Unable to refrain from use of the following:
– Short acting bronchodilators (SABA) within 4 hours before pulmonary function, DLCO, and 6MWT assessments
– Once daily, long-acting bronchodilators within 24 hours before pulmonary function, DLCO, and 6MWT assessments
– Twice daily, long-acting bronchodilators within 12 hours before pulmonary function testing, DLCO, and 6MWT assessments
• Known post-bronchodilator response in FEV1 and/or FVC =12% and =200 mL, respectively
• Receipt of an investigational drug within 4 weeks, or 5 half-lives, whichever is longer, prior to screening
• Previous treatment with PRM-151
• History of severe allergic reaction or anaphylactic reaction to a biologic agent
• Clinically significant abnormality on ECG during screening including prolonged corrected QT interval >450 ms (for men) or >470 ms (for women) based on the Fridericia correction formula; or laboratory tests (hematology, serum chemistry, and urinalysis) that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient
• Any of the following laboratory abnormalities during screening:
– ALT and/or AST =2.5 x upper limit of normal (ULN)
– Total bilirubin =2 x ULN
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 8 weeks after the final dose of PRM-151 Women of childbearing potential must have a negative serum pregnancy test result within 30 days prior to initiation of study drug.
• 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 of screening
• Receiving systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks prior to 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 [interferon gamma release assay])
– 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 <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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Absolute change in forced vital capacity (FVC [mL])<br> NAME OF THE RESULT: Absolute change from baseline to Week 52 in forced vital capacity (FVC [mL])<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: baseline to Week 52
- Secondary Outcome Measures
Name Time Method