Phase 1b Double-Blind, Placebo-Controlled, Ascending Dose Trial: ORIN1001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- Orinove, Inc.
- Enrollment
- 24
- Locations
- 11
- Primary Endpoint
- Body Temperature
- Status
- Suspended
- Last Updated
- 11 months ago
Overview
Brief 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.
Detailed 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.
Investigators
Eligibility Criteria
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 \[Ofev®\] OR neither) is acceptable, provided stable dosing of the drug for at least 8 consecutive weeks immediately prior to signing the ICF.
- •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.
- •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:
- •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) \>
- •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).
- •Forced vital capacity (FVC) ≤40% of predicted normal per site pulmonary function lab protocol.
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤30% of predicted normal as calculated according to the site pulmonary function lab protocol.
- •Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio \< 0.
Arms & Interventions
Placebo - 25 mg
Placebo comparator for ORIN1001 at 25 mg
Intervention: Placebo
Placebo - 50 mg
Placebo comparator for ORIN1001 at 50 mg
Intervention: Placebo
Placebo - 100 mg
Placebo comparator for ORIN1001 at 100 mg
Intervention: Placebo
50 mg ORIN1001 (active)
50 mg ORIN1001
Intervention: ORIN1001
100 mg ORIN1001 (active)
100 mg ORIN1001
Intervention: ORIN1001
25 mg ORIN1001 (Active)
25 mg ORIN1001
Intervention: ORIN1001
Outcomes
Primary Outcomes
Body Temperature
Time Frame: Up to 60 days
Measurement of body temperature
12-lead ECG
Time Frame: Up to 60 days
Cardiovascular evaluation to determine intervals including QTc interval
Heart Rate
Time Frame: Up to 60 days
measurement of heart rate
Blood pressure
Time Frame: Up to 60 days
measurement of blood pressure
Respiratory Rate
Time Frame: Up to 60 days
Measurement of respiratory rate
DLCO - Assessment of diffusion capacity
Time Frame: Up to 60 days
Lung test to assess diffusion capacity
Serum Clinical Chemistry analysis
Time Frame: Up to 60 days
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
Whole blood Hematology analysis
Time Frame: Up to 60 dys
WBC, RBC, Hb, HCT, MCV, MCH, MCHC, Neu, Lymphocytes, EOS, Bas, PLT
Body weight
Time Frame: Up to 60 days
Body weight in kg
Whole blood Coagulation Parameters
Time Frame: Up to 60 days
PT, APTT, INR
Urinalysis
Time Frame: Up to 60 days
Bilrubin, glusoe, ketones, leukocytes, nitrite, blood, pH, specific gravity, protein, urobilinogen
Concomitant medications
Time Frame: Up to 60 days
Evaluation of other medications taken currently with investigative drug
Physical examination
Time Frame: Up to 60 days
Medical Health examination, medical history, medicine history, reproductive history, baseline information
Spirometry
Time Frame: Up to 60 days
Pulmonary Function Tests: Forced vital capacity (FVC), Forced expiratory volume (FEV)
Height
Time Frame: Up to 60 days
Height in cm
Body mass index (BMI)
Time Frame: Up to 60 days
Calculation of BMI using weight (kg) and height (cm)
Secondary Outcomes
- Blood collection to measure drug concentration over time(Up to 29 days)