cryptogenic fibrosing alveolitis
Conditions
Interventions
Patients will receive IV infusions of 10 mg/kg PRM 151 over approximately 50*70
minutes, with dose based on the patient*s weight recorded at each visit (for
loading or reloading doses, weight taken
* Urinalysis collection has been updated from every 24 weeks to every 12 weeks
to align with the collection of urine for optional biomarker sampling (Appendix
1).
* It has been clarified that study
Sponsors
Hoffmann-La Roche
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: * Signed Informed Consent Form * In the opinion of the Principle Investigator, participation in the study is in the best interest of the patient * Ability to comply with the requirements of the study protocol, according to the investigator*s best judgment * Taken part in a previous study of PRM-151, as follows: o Participated in Study PRM-151-202 (completed the 28-week placebo-controlled period and entered the OLE), and tolerated the study drug in the opinion of the investigator (Cohort A) OR o Completed study treatment in Study WA42293 (Cohort B) OR o Participated in Study WA42293 but have discontinued from study treatment (Cohort C; patients who completed treatment in Study WA42293, but no longer wish to take PRM-151 may also join Cohort C) * For women of childbearing potential: 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 methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. * 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, inf
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: * Received any experimental treatment other than PRM-151 within 4 weeks or five half-lives of the experimental drug, whichever is longer, prior to the first dose in the OLE study * 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 at the first visit of the OLE, or within 2 weeks of the first visit for patients joining Cohort A (from Study PRM-151-202) * History of smoking (including cigarette, cannabis, cigar, pipe, and vaping) within 3 months prior to the first visit in the OLE * History of alcohol or substance use disorder within 2 years prior to the first visit of the OLE or known or suspected active alcohol or substance-use disorder. * History of severe allergic reaction or anaphylactic reaction to PRM-151 * Clinically significant abnormality on ECG during eligibility assessment that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient. * Prolonged corrected QT interval > 450 ms (for men) or > 470 ms (for women) based on the Fridericia correction formula. * Clinically significant laboratory test abnormalities (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 known at the time of the first visit - ALT and/or AST *2.5*upper limit of normal (ULN) - Total bilirubin *2*ULN * Pregnant or breastfeeding, or intending to become pregnant during the study (for Cohort A or B patients)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| This study will evaluate the long-term safety, efficacy and pharmacokinetics of open label PRM 151 in patients with idiopathic pulmonary fibrosis (IPF). Specific objectives and corresponding endpoints for the study are outlined below. The safety objective for this study is to confirm the long term safety and tolerability of 10 mg/kg of PRM 151 administered every 4 weeks (Q4W) via intravenous (IV) infusion plus standard of care (SOC) treatment, on the basis of the following endpoints: • Incidence and severity of all adverse events (AEs), 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]) • Incidence and severity of infusion related reactions (IRRs) and other AEs of special interest • Proportion of patients permanently discontinuing study treatment due to AEs • Change from baseline of targeted clinical laboratory test results The efficacy objectives are to assess the long term efficacy of 10 mg/kg PRM 151 plus SOC (excluding lung transplantation) administered Q4W via IV infusion on the basis of the following endpoints: • Annual rate of decline in forced vital capacity (FVC [mL]) • Annual rate of change in 6 minute walk distance (6MWD) • Annual rate of decline in FVC% predicted • Progression free survival, defined as time to first occurrence of *10% absolute decline in % predicted FVC, *15% relative decline in 6MWD, or death • Change from baseline in University of California, San Diego Shortness of Breath Questionnaire (UCSD SOBQ) • Change from baseline in St. George Respiratory Questionnaire (SGRQ) Total Score • Change from baseline in carbon monoxide diffusing capacity (DLCO) • Survival, as measured by all cause mortality | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory analyses may also be performed for additional measures and subgroups of interest including concurrent use of IPF treatment and geographic region. Details of all such analyses will be provided in the Statistical Analysis Plan (SAP). Pharmacokinetic Objectives The pharmacokinetic (PK) objective for this study is to characterize pharmacokinetics of PRM 151 in patients with IPF (from Cohort A only), on the basis of the following endpoint: • Serum concentrations of PRM 151 at specified timepoints The exploratory PK objectives are to evaluate the potential relationship between drug exposure and the efficacy and safety of PRM 151 on the basis of the following endpoints: • Relationship between PK for PRM 151 and efficacy endpoints • Relationship between PK for PRM 151 and safety endpoints The immunogenicity objective for this study is to evaluate the immune response to PRM 151 in patients with IPF (from Cohort A only) on the basis of the following: • Prevalence of ADAs at baseline and incidence of ADAs during the study The exploratory immunogenicity objective for this study is to evaluate potential effects of ADAs on the basis of the following: • Relationship between ADA status and efficacy, safety, or PK endpoints The exploratory biomarker objective for this study (from Cohort A only) is to identify and/or evaluate biomarkers that can provide evidence of PRM 151 activity and the duration of that activity (i.e., pharmacodynamic biomarkers), are associated with acquired resistance to PRM 151, are associated with susceptibility to developing AEs or can lead to improved AE monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and understanding of disease biology and drug safety, on the basis of the following endpoint: • Relationship between biomarkers in blood and efficacy, safety, PK, immunogenicity, or other biomarker endpoints. The exploratory health status utility objective for this study is to evalu | — |
Countries
Netherlands
Outcome results
None listed