A study to assess the efficacy, safety and pharmacokinetics of PLN-74809 in participants with idiopathic pulmonary fibrosis
- Conditions
- Idiopathic pulmonary fibrosis (IPF)MedDRA version: 21.1Level: PTClassification code 10021240Term: Idiopathic pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-002709-23-NL
- Lead Sponsor
- Pliant Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 112
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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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
Screening
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-li
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Assessment of the safety and tolerability of PLN-74809 ;Secondary Objective: Assessment of pharmacokinetics (PK) of PLN-74809;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.;Primary end point(s): Primary Safety Endpoint<br>Nature and proportion of AEs between PLN-74809 and placebo groups (descriptive)<br>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.
- Secondary Outcome Measures
Name Time Method