A study to assess the efficacy, safety and pharmacokinetics of PLN-74809 in participants with idiopathic pulmonary fibrosis
- Conditions
- idiopathic pulmonary fibrosisMedDRA version: 20.0Level: SOCClassification code 10038738Term: Respiratory, thoracic and mediastinal disordersSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-002709-23-IT
- Lead Sponsor
- Pliant Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
1. Participants, aged 40 years or older.
2. Diagnosis of IPF for up to 5 years prior to screening based on
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 either
surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy,
and/or bilateral oophorectomy at least 26 weeks before the Screening
Visit) or post-menopausal, defined as spontaneous amenorrhea for at
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least 2 years
8. Female participants of childbearing potential (i.e., ovulating, premenopausal,
and not surgically sterile) and all male participants with
sexual partners of childbearing potential must use highly effective
methods of birth control during their participation in the study and for
90 days after the last administration of study drug. Hormonal
contraceptives are not allowed. Highly effective methods of birth control
are defined as those with 99% or greater efficacy.
9. Participants must agree to abstain from sperm or egg donation
through 90 days 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 84
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 fibrotic changes is greater than the extent of
emphysema on the most recent HRCT scan (as determined by central
reader)
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. Hepatic impairment or 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
d. Significant 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
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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 trial with an investigational agent in the
30 days prior to Screening
22. Likely to have lung transplantation during the study (being on
transplantation list is acceptable)
23. Any medical condition that,
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 following daily<br>administration for up to 12 weeks;Secondary Objective: Assessment of pharmacokinetics (PK) of PLN-74809;Primary end point(s): Nature and proportion of AEs between PLN-74809 and placebo groups<br>(descriptive)<br>Safety data from all participants who received at least one dose of study<br>drug will be incorporated into the final safety analysis. Further details of<br>the safety analyses will be provided in the SAP. AEs will be collected<br>from the time the participant signs the ICF until the last study visit.<br>Treatment-emergent adverse events (TEAEs) are defined as AEs that<br>emerged or worsened in severity after the first administration of study<br>drug.;Timepoint(s) of evaluation of this end point: week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): a. Secondary Pharmacokinetic Endpoints<br>Plasma PLN-74809 concentrations (total and unbound concentrations) at<br>each sampling time point will be presented in listings and descriptive<br>summary statistics by dose and visit. The data will also be presented<br>graphically.<br>b. Secondary Pharmacodynamic Endpoints<br>Urine, plasma and serum samples will be analyzed for biomarkers<br>(presence or actual concentration). These samples will be used to<br>determine the levels of these markers in participants and the<br>relationship between these markers. Results will be presented by<br>listings, descriptive summary statistics and in graphical form by treatment and dose and expressed as the relative change (and or absolute) for each participant.;Timepoint(s) of evaluation of this end point: week 12