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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
St. Francis Sleep, Allergy & Lung Institute
Clearwater, Florida, United States
Mayo Clinic Hospital
Jacksonville, Florida, United States
Avanza Medical Research
Pensacola, Florida, United States
Coastal Pulmonary and Critical Care
St. Petersburg, Florida, United States
Loyola University Medical Center
Maywood, Illinois, United States
University of Iowa Hospital
Iowa City, Iowa, United States
Infinity Medical Research
North Dartmouth, Massachusetts, United States
Hannibal Clinic
Hannibal, Missouri, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
Duke University Hospital
Durham, North Carolina, United States
...and 1 more locations
Blood pressure
measurement of blood pressure
Time frame: Up to 60 days
Heart Rate
measurement of heart rate
Time frame: Up to 60 days
Respiratory Rate
Measurement of respiratory rate
Time frame: Up to 60 days
Body Temperature
Measurement of body temperature
Time frame: Up to 60 days
12-lead ECG
Cardiovascular evaluation to determine intervals including QTc interval
Time frame: Up to 60 days
Serum Clinical Chemistry analysis
ALT, albumin, ALP, AST, BUN, Ca, Cl, Cholesterol, Creatinine, CK, CA, Elastase, GGT, glucose, HDL, LDH, lipase, LDL, phosphorus, sodium, Total bilirubin, Total protein, Triglycerides, Uric acid, Lipid panel
Time frame: Up to 60 days
Whole blood Hematology analysis
WBC, RBC, Hb, HCT, MCV, MCH, MCHC, Neu, Lymphocytes, EOS, Bas, PLT
Time frame: Up to 60 dys
Whole blood Coagulation Parameters
PT, APTT, INR
Time frame: Up to 60 days
Urinalysis
Bilrubin, glusoe, ketones, leukocytes, nitrite, blood, pH, specific gravity, protein, urobilinogen
Time frame: Up to 60 days
Concomitant medications
Evaluation of other medications taken currently with investigative drug
Time frame: Up to 60 days
Physical examination
Medical Health examination, medical history, medicine history, reproductive history, baseline information
Time frame: Up to 60 days
Body weight
Body weight in kg
Time frame: Up to 60 days
Spirometry
Pulmonary Function Tests: Forced vital capacity (FVC), Forced expiratory volume (FEV)
Time frame: Up to 60 days
Height
Height in cm
Time frame: Up to 60 days
Body mass index (BMI)
Calculation of BMI using weight (kg) and height (cm)
Time frame: Up to 60 days
DLCO - Assessment of diffusion capacity
Lung test to assess diffusion capacity
Time frame: Up to 60 days
Blood collection to measure drug concentration over time
Blood collection for evaluation of ORIN1001 exposure. Measurements will assess half life, exposure, maximum concentration, time to maximum concentration and accumulation ratios
Time frame: Up to 29 days
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