|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Idiopathic pulmonary fibrosis (IPF)
|Medical condition in easily understood language
|Idiopathic Pulmonary Fibrosis (IPF)
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|Idiopathic pulmonary fibrosis
|System Organ Class
|10038738 - Respiratory, thoracic and mediastinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Assessment of the safety and tolerability of PLN-74809
|Secondary objectives of the trial
|Assessment of pharmacokinetics (PK) of PLN-74809
|Trial contains a sub-study
|Principal inclusion criteria
|1. Participants, aged 40 years or older.
2.Diagnosis of IPF for up to 5 years prior to screening based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/ Japanese Respiratory Society (JRS)/ Latin American Respiratory Society (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 postmenopausal.
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 with female partners of childbearing potential 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 sperm or egg 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).
|Principal exclusion criteria
|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 high-resolution computerized tomography (HRCT) scan (as determined by central reader); a) HRCT scan performed within 2 years of the screening date may be used
7. Diagnosis of 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
c. Uncontrolled clinically significant arrhythmias (e.g., potentially resulting in 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, including, but not limited to, suspected infection with COVID-19
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 (i.e., strong) inhibitors or inducers of cytochrome P450 (CYP) 3A4 and Pglycoprotein (P-gp) (e.g., itraconazole), breast cancer resistance protein (BCRP) or organic anion transporting polypeptide (OATP) 1B1/1B3 transporters
|E.5 End points
|Primary end point(s)
|Primary Safety Endpoint
Nature and proportion of AEs between PLN-74809 and placebo groups (descriptive)
Safety data from all participants who received at least one dose of study drug will be incorporated into the final safety analysis. Further details of the safety analyses will be provided in the SAP. AEs will be collected from the time the participant signs the ICF until the last study visit. Treatment-emergent adverse events (TEAEs) are defined as AEs that emerged or worsened in severity after the first administration of study drug.
|Timepoint(s) of evaluation of this end point
|AEs will be collected from the time the participant signs the ICF until the last study visit.
|Secondary end point(s)
|a. Secondary Pharmacokinetic Endpoints
Plasma PLN-74809 concentrations (total and unbound concentrations) at each sampling time point will be presented in listings and descriptive summary statistics by dose and visit. The data will also be presented graphically.
Further details of the analyses will be provided in the SAP to be prepared and agreed prior to final ‘database lock’ at the end of the study. The PK analysis plan and report may be prepared separately from the SAP as appropriate.
b. Secondary Pharmacodynamic Endpoints
Urine, plasma and serum samples will be analyzed for biomarkers (presence or actual concentration). These samples will be used to determine the levels of these markers in participants and the relationship between these markers. Results will be presented by listings, descriptive summary statistics and in graphical form by treatment and dose and expressed as the relative change (and or absolute) for each participant.
In addition, relationships between PK and PD may be evaluated in an exploratory fashion and presented in graphical manner.
|Timepoint(s) of evaluation of this end point
|Day 1, Week 4, Week 12 and Week 14
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days