Principal Investigator: Mary  Scholand
Keywords: Pliant , IPF , Idiopathic Pulmonary Fibrosis , PLN-74809 Department: Pulmonary
IRB Number: 00138725 Co Investigator: Sean Callahan
Specialty: Pulmonary
Sub Specialties: Pulmonary Fibrosis
Recruitment Status: Not yet recruiting

Contact Information

Cassie Larsen
cassie.larsen@hsc.utah.edu
8015815811

Simple Summary

A randomized, double-blind, dose-ranging, placebo-controlled Phase 2a evaluation of the safety, tolerability and pharmacokinetics of PLN-74809 in participants with idiopathic pulmonary fibrosis (IPF).

Inclusion Criteria

Each participant must meet the following criteria to be enrolled in this study:
1. Participants, aged 40 years or older
2. Diagnosis of IPF for up to 5 years based upon ATS/ERS/JRS/ALAT 2018 guidelines (Raghu et al, 2018)

Note: If IPF diagnosis is within >3 to <5 years at screening, the participant must have evidence of progression within the last 24 months, as defined by decline in FVC percent predicted based on a relative decline of >5%
3. FVC percent of predicted ≥45%; historical FVC for entry in the study is permitted if within 1 month of screening
4. Diffusing capacity for carbon monoxide (DLco) (hemoglobin-adjusted) ≥30%; historical DLco for entry in the study is permitted if within 1 month of screening
5. Participants currently receiving treatment for IPF with nintedanib or pirfenidone are
allowed, provided these drugs have been given at a stable dose for at least 3 months
before the Screening Visit and are expected to remain unchanged during the study (stable dose is defined as the highest dose tolerated by the participant during >3 months)
6. Estimated glomerular filtration rate ≥ 50 mL/min, according to the Cockcroft-Gault equation

7. Female participants of non-childbearing potential must be surgically sterile or post-menopausal
8. Female participants of childbearing potential must use a contraceptive method with a failure rate of <1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for  1 month after the last dose of study treatment.

Male participants must agree to use contraceptive measures or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the last dose of study treatment.

9. Participants must agree to abstain from egg or sperm donation for the duration of the study through to 3 months or 1 month, respectively, after administration of the last dose of study drug
10. Able to read and sign a written informed consent form (ICF)

*If a partner becomes pregnant, an amendment will be submitted to add this vulnerable population and a pregnant partner consent will be submitted for approval.

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from the study.
1. Receiving any non-approved agent intended for treatment of fibrosis in IPF
2. Forced expiratory volume during the first second (FEV1) over the forced vital capacity
(FVC) ratio (FEV1/FVC ratio) <0.7 at Screening
3. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia,
or sinusitis that can affect FVC measurement during Screening or at Randomization.
4. Any other condition that prevents the correct assessment of spirometry performance (for
example a broken rib or chest pain of other origin that prevents adequate forced
breathing)
5. Known acute IPF exacerbation or suspicion by the Investigator of such, within 6 months
of Screening

6. The extent of emphysema is greater than the extent of fibrotic changes on the most recent HRCT scan (as determined by central reader). A HRCT scan performed within 2 years of the screening date may be used. (*NOTE: There is a discrepancy between the protocol and NTFs as to whether this should read "is" or "is not" greater than. CRO confirmed it should read "is not" greater than. This will be corrected in the protocol in a future amendment.)

7. Severe pulmonary hypertension
8. Smoking of any kind (not limited to tobacco) within 3 months of Screening or unwilling
to avoid smoking throughout the study
9. Lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and/or during the screening period

10. History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, resected noninvasive cutaneous squamous cell carcinoma, or treated cervical carcinoma in situ
11. End-stage liver disease
12. Renal impairment or end-stage kidney disease requiring dialysis
13. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within
the 6 months prior to Screening, including but not limited to the following:
a. Unstable angina pectoris or myocardial infarction
b. Congestive heart failure requiring hospitalization during the 6 months prior to
Screening
c. Uncontrolled clinically significant arrhythmias (e.g. resulting i n health care utilization or hospitalization)
d. Any clinically relevant electrocardiogram (ECG) abnormalities, including but not limited to, QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec for males or > 460 msec for females at the Screening visit (including Day -1) or prior to administration of the initial dose of study drug.
14. Any of the following liver function test criteria above specified limits: total bilirubin
>1.5× the upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) >3× ULN; alkaline phosphatase >2.5× ULN

Note: participants currently receiving nintedanib or pirfenidone as IPF SoC treatment, who have previously presented any liver function test elevations associated with nintedanib or pirfenidone treatment greater than that described above or resulting in dose reduction, treatment interruption, or discontinuation are not eligible.
15. Any of the following at Screening: hemoglobin <10.0 g/dL, or neutrophils <1500 /mm3,
or platelets <100,000 /mL
16. Pregnant or lactating females

17. Daily use of phosphodiesterase-5 (PDE-5) inhibitor drugs (e.g., sildenafil, tadalafil, other) (Note: Intermittent use for erectile dysfunction is allowed.)
18. A medical or surgical condition known to affect drug absorption (e.g., major gastric
surgery)
19. Surgical procedures planned to occur during the study period
20. Uncontrolled systemic arterial hypertension
21. Has participated in a clinical study with an investigational agent in the 30 days prior to
Screening or 5 half-lives of the investigational drug, whichever is longer
22. Likely to have lung transplantation during the study (being on transplantation list is
acceptable)
23. Any medical condition that, in the opinion of the Investigator, may make candidates not
suitable for the study

24. Hypersensitivity to PLN-74809 or to any of the excipients, or placebo
25. Currently receiving and expected to remain on treatment during the study with: potent inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2C9 or 2C19; potent inhibitors or inducers of P glycoprotein (P-gp), breast cancer resistance protein (BCRP), or organic anion transporting polypeptide (OATP) 1B1/1B3 transporters; digoxin (a P-gp substrate with a narrow therapeutic window)