| Eligibility |
Inclusion Criteria:
1. 40-80 years of age (inclusive) when signing the Informed Consent.
2. Diagnosis of IPF or likely IPF per 2018 American Thoracic Society and European
Respiratory Society (ATS/ERS) criteria:
- Study Investigator will confirm IPF diagnosis based on Interstitial Lung Disease
(ILD) in consultation with relevant experts through a review of the subject's
history, high-resolution computerized tomography (HRCT) scan, and lung biopsy (if
applicable).
- A lung biopsy is not required in the setting of a compatible clinical history and
usual interstitial pneumonia (UIP) or probable UIP per HRCT.
- Study Investigators will verify that a diagnosis of IPF and an HRCT were obtained
within 7 years prior to signing the ICF.
3. Continued SOC IPF therapy (consisting of pirfenidone [Esbriet®] OR nintedanib [Ofev®]
OR neither) is acceptable, provided stable dosing of the drug for at least 8
consecutive weeks immediately prior to signing the ICF.
4. The effect of ORIN1001 on the developing human fetus, if any, is unknown. Therefore,
for the duration of study participation:
- Women who are postmenopausal for < 1 year before the Screening and not otherwise
sterile (e.g., due to a surgical procedure) may be considered of child-bearing
potential and require a negative pregnancy test prior to study registration. They
must agree to (a) use effective contraception (i.e., hormonal or barrier method
of birth control when engaged in heterosexual intercourse) or (b) abstinence
throughout the study period AND for 4 weeks after final dosing with the IMP.
- Men who are not otherwise sterile (e.g., due to a surgical procedure) must agree
not to donate sperm and use effective contraception (i.e.,hormonal or barrier
method of birth control when engaged in heterosexual intercourse) or abstinence
throughout the study period AND for at least 16 weeks (due to the sperm life
cycle) after final dosing with the IMP.
5. Written informed consent must be given prior to any study-related procedure that is
not part of standard medical care, understanding that the subject may withdraw it at
any time without prejudice to future treatment.
Exclusion Criteria:
1. Screening lab values that fail to meet the following criteria will render the subject
ineligible for study participation:
- Platelet count <100 × 109/L. Repeat measurements may be performed, but
transfusion, in order to meet eligibility criteria, is not allowed.
- Hemoglobin <12.9 g/dL (men) and <11.9 g/dL (women).
- Prothrombin time (PT) or partial thromboplastin time (PTT) >1.5 × upper limit of
normal; international normalized ratio (INR) >2.
- Aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >1.5 × upper
limit of normal (ULN).
- Serum glutamic-oxaloacetic transaminase [SGOT] or serum glutamic pyruvic
transaminase [SGPT]) >2.0 × ULN.
- Kidney disease with estimated glomerular filtration rate <60 mL/min).
2. Forced vital capacity (FVC) =40% of predicted normal per site pulmonary function lab
protocol.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) =30% of predicted normal as
calculated according to the site pulmonary function lab protocol.
4. Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio < 0.7.
5. Documented IPF exacerbation within 3 months of signing the ICF (e.g., >5% or 10%
change in FVC and DLCO, respectively).
6. Listing for lung transplantation, defined as the assignment of a lung allocation score
or acceptance on the waiting list for lung transplantation.
7. Current and/or uncontrolled cardiovascular condition (e.g., clinically significant
arrhythmia or hypertension), >Class II heart failure per New York Heart Association
criteria, unstable angina, myocardial infarction, coronary syndrome) within 6 months
of Screening which, as judged by the Investigator, might put the subject at risk
because of participation in the study.
8. Known cirrhotic liver, chronic liver, or biliary disease (with the exception of
Gilbert's syndrome or asymptomatic gallstones). Liver cirrhosis with portal
hypertension and active liver infection are exclusionary (note: cured hepatitis C is
not considered active).
9. Gastrointestinal disease (e.g., active bleeding or ulcers) or procedure that could
interfere with oral absorption or tolerance of the IMP, including difficulty
swallowing.
10. Diarrhea >Grade 1 (i.e., increase of >4 stools per day OR >1 watery stool per day OR
moderate increase in ostomy output compared to baseline) will render a subject
ineligible for participation in this study. Anti-diarrheal medication (e.g.,
loperamide, sold under the brand name Imodium®, among others) is allowed.
11. Active malignancy within the past 12 months or ongoing active cancer treatment
(surgery, radiotherapy, chemotherapy or immunotherapy), except for adequately treated
Stage 1 cancer, nonmelanoma skin cancer, or in situ cervical cancer. Cancer in
complete remission or requiring only maintenance therapy (e.g., tamoxifen for breast
cancer) is not considered active.
12. Known bleeding risk due to platelet dysfunction, or inherited or acquired clotting
factor deficiency (e.g., von Willebrand disease, hemophilia).
13. Major trauma or surgery including but not limited to operations involving a major
organ (e.g., the cranium, chest, abdomen, or pelvic cavity) OR requiring a lengthy
recovery period (e.g., arthroplasty) within 3 months of signing the ICF; or expected
surgery during the trial period.
14. Central nervous system hemorrhagic event within 12 months of signing ICF; brain
arterio-venous malformation (AVM) or moderate-to-severe ischemic stroke within 6
months of signing ICF.
15. Concurrent use of full-dose therapeutic anti-coagulation (e.g., vitamin K antagonist,
dabigatran, hirudin, direct factor Xa inhibitors) or high dose anti-platelet therapy.
Aspirin <81 mg/day, prophylactic subcutaneous (SC) heparin or SC low-molecular weight
heparin for deep vein thrombosis prophylaxis or heparin flush to maintain intravenous
catheter patency are allowed.
16. Long-term use of nonsteroidal anti-inflammatory agents, defined as >4 days per week.
17. Receipt of hematopoietic growth factors, blood or blood product transfusion within 1
week of the first dose of IMP.
18. Disqualifying treatments within 60 days or 5 half-lives (whichever is longer) from
Randomization include:
- Systemic corticosteroids (>10 mg prednisone or equivalent).
- Systemic immunosuppressive therapy.
- Investigational agent other than study IMP.
19. Recreational drug use (including amphetamines, cocaine, barbiturates, opiates,
benzodiazepines, phencyclidine, and cannabinoids) for the duration of study
participation.
20. Clinically significant laboratory abnormality, medical or psychological comorbidity,
or concurrent medication that could compromise subject safety, data integrity or
requirements for study participation, per site Investigator in consultation with the
Sponsor.
21. Inability to attend in-person appointments per current clinical site COVID-19
guidelines and restrictions.
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