Inclusion Criteria:
To be eligible for participation in this study, subjects must meet all the following:
Age. 1. At least 40 to 85 years of age, inclusive, at the time of signing the Informed Consent
Form (ICF).
Type of Subject and Disease Characteristics. 2. Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) as defined by ATS/ERS/JRS/ALAT
guidelines.
3. IPF diagnosis within the past 7 years, with onset defined as the date of the first
recorded diagnosis of IPF by HRCT and/or surgical biopsy or other appropriate tissue
sample (e.g., cryobiopsy) in the medical history.
4. Interstitial pulmonary fibrosis defined by HRCT scan at Screening, with evidence of
≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the
whole lung. NOTE: HRCT scans will be assessed locally by the investigator prior to
randomization. If a recent HRCT scan (within 3 months prior to Screening) is
available, it can be utilized for screening purposes.
5. Observed time to disease progression (FVCpp) value >45% and <95% at Screening and Day
1 (prior to randomization).
6. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted and
corrected by hemoglobin (Hb) value ≥25% and ≤90% at Screening (determined locally). If
a DLCO is available within 3 months prior to Screening, it can be utilized for
screening purposes. NOTE: Both FVC and DLCO testing must be representative of the IPF
underlying disease (i.e., have been obtained in absence of an acute respiratory event
[e.g., lung infection, cold]) or other events that are known to affect pulmonary
function test (PFT) results (e.g., broken rib, chest pain, other).
Contraception Related Contraception use by men or women should be consistent with
local regulations regarding the methods of contraception for those participating in
clinical studies.
7. Male subjects with partners of childbearing potential must use condom and female
subjects of childbearing potential (including those <1 year postmenopausal) must use a
highly effective method of contraception per Clinical Trial Facilitation Group (CTFG)
recommendation during the conduct of the study, and for 30 days after the last dose of
IP (males only during exposure to IP).
Women not of childbearing potential are defined as:
1. Post-menopausal women (defined as at least 12 months with no menses without an
alternative medical cause); in women < 45 years of age, a high follicle
stimulating hormone (FSH) level in the postmenopausal range may be used to
confirm a postmenopausal state in women not using hormonal contraception or
hormonal replacement therapy; OR. 2. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy,
or bilateral tubal ligation/occlusion, at least 6 weeks prior to Screening; OR. 3. Have a congenital or acquired condition that prevents childbearing. Informed
Consent. 8. Capable of giving signed informed consent that includes compliance with the
requirements and restrictions listed in the ICF and in this protocol Other. 9. Treatment with approved background IPF therapy such as nintedanib or pirfenidone will
be allowed as long as subjects are on a stable dose for at least 12 weeks prior to the
first dose of the Investigational product and throughout the treatment period.
Exclusion Criteria:
Subjects meeting any of the following exclusion criteria are not eligible to be randomized
into the study:
Medical Conditions. 1. Evidence of significant obstructive lung disease by any of the following criteria:
- (1)
forced expiratory volume in 1 second (FEV1)/FVC) ratio <0.70, or (2) extent of
emphysema greater than the extent of fibrosis on HRCT.
NOTE: This requires
confirmation by the investigator prior to randomization.
2. Interstitial lung disease (ILD) other than IPF, including but not limited to any of
the other types of idiopathic interstitial pneumonias; lung diseases related to
exposure to fibrogenic agents or other environmental toxins or drugs; other types of
occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases;
systemic diseases, including vasculitis, infectious diseases, and connective tissue
diseases. In cases of uncertain diagnosis, serological testing and/or review by
multi-disciplinary team should be performed to confirm diagnosis of IPF vs. other
types of ILD.
3. Sustained improvement in the severity of IPF during the 12 months prior to Screening,
based on changes in FVC, DLCO, and/or HRCT scans of the chest.
4. History of other types of respiratory diseases, including diseases or disorders of the
airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that,
in the opinion of the investigator, would impact the primary protocol endpoint or
otherwise preclude the subject's participation in the study.
5. History of liver dysfunction including patients with moderate (Child Pugh B) or severe
(Child Pugh C) impairment or disordered coagulation.
6. Medical conditions (e.g., myocardial infarction/stroke within the past 6 months), or
logistical challenges that in the opinion of the investigator preclude the subject's
adequate participation in the study.
7. Poorly controlled chronic heart failure (New York Heart Association Class 3 or above);
clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary
arterial hypertension requiring specific treatment that, in the opinion of the
investigator, would preclude the subject's participation in the study.
8. Ongoing acute IPF exacerbation, or suspicion of such process during Screening or
randomization, including hospitalization due to acute IPF exacerbation within 4 weeks
prior to or during Screening.
9. High likelihood of lung transplantation (in the opinion of the Investigator) within 6
months after Day 1.
10. Body weight less than 40 kg (88.18 lb) or anorexia.
11. Any condition (other than IPF) that is likely to result in the death of the subject
within the next year.
12. Any current malignancy (this does not include localized cancer such as basal or
squamous cell carcinoma of skin). Any history of malignancy likely to result in
mortality or requiring significant medical or surgical intervention within the next
year.
13. The investigator judges that the subject will be unable to fully participate in the
study and complete it for any reason, including inability to comply with study
procedures and treatment, addiction, or any other relevant medical or psychiatric
conditions.
14. Female subjects who are pregnant or breastfeeding.
Diagnostic Assessments. 15. The following laboratory parameters are excluded:
1. Hb <10 g/dL (100 g/L)
2. White blood cells (WBC) <3000/μL (<3000/mm3)
3. Platelet count <70,000/μL (<70,000/mm3)
4. Serum creatinine ≥1.5 x upper limit of normal (ULN)
5. Glomerular filtration rate (GFR) < 60ml/m/1.73 or evidence of acute kidney injury. 6. Serum total bilirubin >1.5 x ULN. 7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x
ULN, or serum alkaline phosphatase ≥2 x ULN.
Excluded Therapies. 16. Daily use of phosphodiesterase type 5 (PDE-5) inhibitor drugs (e.g., sildenafil,
tadalafil) except for treatment of severe pulmonary artery hypertension. 17. Use of any therapeutics with strong inhibitors and strong inducers of CYP3A4 or CYP2C8
[e.g., rifampicin, ketoconazole, phenytoin, ritonavir, macrolide antibiotics (e.g.,
telithromycin), and carbamazepine] is also prohibited.
Prior/Concurrent Clinical Study Experience. 18. Previous exposure to cudetaxestat. 19. Use of any investigational drugs or unapproved therapies, or participation in a
clinical study with an investigational new drug, within 30 days prior to first
Screening visit.
Other Exclusions. 20. History of allergic or anaphylactic reaction to cudetaxestat, or to any component of
the excipient.
21. History of intolerance to nintedanib or pirfenidone (e.g., arterial thromboembolic
disease, bleeding, proteinuria, or photosensitivity)
22. Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the
study
