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) (INTEGRIS-IPF)
- Conditions
- idiopathic pulmonary fibrosis10027665
- Registration Number
- NL-OMON54907
- Lead Sponsor
- Pliant Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
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)
Exclusion Criteria:
1. Receiving any nonapproved agent intended for treatment of fibrosis in IPF
2. Forced expiratory volume during the first second (FEV1) over the 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. 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method