Phase 1b Double-Blind, Placebo-Controlled, Ascending Dose Trial: ORIN1001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

  • STATUS
    Recruiting
  • days left to enroll
    56
  • participants needed
    24
  • sponsor
    Orinove, Inc.
Updated on 11 October 2022
pneumonia
nintedanib
idiopathic pulmonary fibrosis
pirfenidone
interstitial lung disease
lung biopsy
ofev
esbriet

Summary

This Phase 1b trial is a double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of oral ORIN1001 at 25 mg, 50 mg or 100 mg administered daily for up to 28 days in adult subjects with idiopathic pulmonary fibrosis (IPF) alone or in conjunction with local Standard of Care for IPF (pirfenidone or nintedanib).

A maximum of 24 evaluable subjects will be required to complete the study. The study will consist of 3 dose cohorts each enrolling a maximum of 8 subjects randomized either to the active (5 subjects) group or placebo (3 subjects) group. Each subject will receive daily oral doses of ORIN1001 or placebo for 28 days.

The safety and pharmacokinetic profile will be evaluated in this study and will include cardiovascular and pulmonary endpoints.

Description

This Phase 1b trial is a double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety and tolerability of oral ORIN1001 at 25 mg, 50 mg or 100 mg administered daily for up to 28 days in adult subjects with idiopathic pulmonary fibrosis (IPF) alone or in conjunction with local standard of care (SOC) for IPF (i.e., pirfenidone or nintedanib).

Approximately 24 evaluable subjects will be required for this study. Eligible subjects will be followed for safety through the dose-limiting toxicity (DLT) evaluation period, defined as 28 days after the first dose of ORIN1001.

In the absence of intolerable toxicity, doses will be escalated sequentially with 8 evaluable subjects receiving a maximum of 28 days of ORIN1001 in once-daily doses of 25 mg (Cohort 1), 50 mg (Cohort 2), or 100 mg (Cohort 3) versus matched placebo. Subjects will be stratified based on local SOC for IPF, defined as the stable daily dose of pirfenidone or nintedanib (or neither) received for at least 8 weeks prior to signing the Informed Consent Form (ICF). ORIN1001 or matched placebo will be administered daily until Day 28, unacceptable toxicity, withdrawal for another reason or study termination.

Safety Endpoints will be evaluated and will include adverse events (AEs), serious adverse events (SAEs), and changes in clinical laboratory evaluations as compared to baseline. Safety variables include but are not limited to: vital signs (blood pressure [BP], heart rate [HR], respiratory rate [RR]) and temperature; twelve-lead ECG; clinical laboratory tests (hematology, coagulation profile, clinical chemistry, and urinalysis); concomitant medications; physical examination; body weight; and pulmonary function tests (forced vital capacity [FVC], forced expiratory volume [FEV], and diffusion capacity [DLCO]) at baseline, End-of- Treatment and Follow-up Visits.

Pharmacokinetic (PK) Endpoints will be evaluated on Day 1 and Day 28 and blood collection samples will be obtained from each subject. Exploratory serum biomarker endpoints will be evaluated to assess lung fibrosis and inflammation.

Details
Condition Idiopathic Pulmonary Fibrosis
Treatment Placebo, ORIN1001
Clinical Study IdentifierNCT04643769
SponsorOrinove, Inc.
Last Modified on11 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

40-80 years of age (inclusive) when signing the Informed Consent
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
Continued SOC IPF therapy (consisting of pirfenidone [Esbriet®] OR nintedanib [Ofev®]
The effect of ORIN1001 on the developing human fetus, if any, is unknown. Therefore, for the duration of study participation
OR neither) is acceptable, provided stable dosing of the drug for at least 8
consecutive weeks immediately prior to signing the ICF
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
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

Screening lab values that fail to meet the following criteria will render the subject ineligible for study participation
Hemoglobin <12.9 g/dL (men) and <11.9 g/dL (women)
Platelet count <100 × 109/L. Repeat measurements may be performed, but transfusion, in order to meet eligibility criteria, is not allowed
Kidney disease with estimated glomerular filtration rate <60 mL/min)
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)
Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio < 0.7
Serum glutamic-oxaloacetic transaminase [SGOT] or serum glutamic pyruvic transaminase [SGPT]) >2.0 × ULN
Documented IPF exacerbation within 3 months of signing the ICF (e.g., >5% or 10% change in FVC and DLCO, respectively)
Forced vital capacity (FVC) ≤40% of predicted normal per site pulmonary function lab
Listing for lung transplantation, defined as the assignment of a lung allocation score or acceptance on the waiting list for lung transplantation
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
protocol
Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤30% of predicted normal as calculated according to the site pulmonary function lab protocol
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)
Gastrointestinal disease (e.g., active bleeding or ulcers) or procedure that could interfere with oral absorption or tolerance of the IMP, including difficulty swallowing
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
Known bleeding risk due to platelet dysfunction, or inherited or acquired clotting factor deficiency (e.g., von Willebrand disease, hemophilia)
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
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
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
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
Long-term use of nonsteroidal anti-inflammatory agents, defined as >4 days per week
Receipt of hematopoietic growth factors, blood or blood product transfusion within 1 week of the first dose of IMP
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
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
Inability to attend in-person appointments per current clinical site COVID-19 guidelines and restrictions
Recreational drug use (including amphetamines, cocaine, barbiturates, opiates
benzodiazepines, phencyclidine, and cannabinoids) for the duration of study
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