A Study to Evaluate PRM-151 in Patients with Idiopathic Pulmonary Fibrosis

Overview

About this study

The purpose of this study is to evaluate the effectiveness, safety, and pharmacokinetics of PRM-151 compared with placebo in patients with idiopathic pulmonary fibrosis (IPF). Specific objectives and corresponding endpoints for the study are outlined below.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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 (Raghu et al. 2018; Appendix 9).
  • 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.
  • 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 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, 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

Exclusion Criteria:

  • Evidence of other known causes of ILD (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.
  • 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 or 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 screening.
  • History of alcohol or substance use disorder within 2 years prior to 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 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 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Eva Carmona Porquera, M.D., Ph.D.

Closed-enrolling by invitation

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"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Shannon Daley C.C.R.C., CCRP

(507) 293-0637

Daley.Shannon@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20510696

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