Evaluation of Oral ORIN1001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

NCT04643769 | Suspended Phase 1 FDA Drug

• 1 other identifier: ORIN1001-002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

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.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (16)

• Blood pressure

  measurement of blood pressure

  Up to 60 days

• Heart Rate

  measurement of heart rate

  Up to 60 days

• Respiratory Rate

  Measurement of respiratory rate

  Up to 60 days

• Body Temperature

  Measurement of body temperature

  Up to 60 days

• 12-lead ECG

  Cardiovascular evaluation to determine intervals including QTc interval

  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

  Up to 60 days

• Whole blood Hematology analysis

  WBC, RBC, Hb, HCT, MCV, MCH, MCHC, Neu, Lymphocytes, EOS, Bas, PLT

  Up to 60 dys

• Whole blood Coagulation Parameters

  PT, APTT, INR

  Up to 60 days

• Urinalysis

  Bilrubin, glusoe, ketones, leukocytes, nitrite, blood, pH, specific gravity, protein, urobilinogen

  Up to 60 days

• Concomitant medications

  Evaluation of other medications taken currently with investigative drug

  Up to 60 days

• Physical examination

  Medical Health examination, medical history, medicine history, reproductive history, baseline information

  Up to 60 days

• Body weight

  Body weight in kg

  Up to 60 days

• Spirometry

  Pulmonary Function Tests: Forced vital capacity (FVC), Forced expiratory volume (FEV)

  Up to 60 days

• Height

  Height in cm

  Up to 60 days

• Body mass index (BMI)

  Calculation of BMI using weight (kg) and height (cm)

  Up to 60 days

• DLCO - Assessment of diffusion capacity

  Lung test to assess diffusion capacity

  Up to 60 days

Secondary Outcomes (1)

• Blood collection to measure drug concentration over time

  Up to 29 days

Other Outcomes (3)

• Exploratory biomarkers to evaluate lung fibrosis

  Up to 60 days

• Quality of Life Questionnaire

  Up to 60 days

• Exploratory biomarkers to evaluate inflammation

  Up to 60 days

Study Arms (6)

25 mg ORIN1001 (Active)

EXPERIMENTAL

25 mg ORIN1001

Drug: ORIN1001

50 mg ORIN1001 (active)

EXPERIMENTAL

50 mg ORIN1001

Drug: ORIN1001

100 mg ORIN1001 (active)

EXPERIMENTAL

100 mg ORIN1001

Drug: ORIN1001

Placebo - 25 mg

PLACEBO COMPARATOR

Placebo comparator for ORIN1001 at 25 mg

Drug: Placebo

Placebo - 50 mg

PLACEBO COMPARATOR

Placebo comparator for ORIN1001 at 50 mg

Drug: Placebo

Placebo - 100 mg

PLACEBO COMPARATOR

Placebo comparator for ORIN1001 at 100 mg

Drug: Placebo

Interventions

ORIN1001 DRUG

Oral tablet - ORIN1001

100 mg ORIN1001 (active); 25 mg ORIN1001 (Active); 50 mg ORIN1001 (active)

Placebo DRUG

Oral tablet - placebo

Placebo - 100 mg; Placebo - 25 mg; Placebo - 50 mg

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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 \< 0.7.
• Documented IPF exacerbation within 3 months of signing the ICF (e.g., \>5% or 10% change in FVC and DLCO, respectively).
• 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.
• Gastrointestinal disease (e.g., active bleeding or ulcers) or procedure that could interfere with oral absorption or tolerance of the IMP, including difficulty swallowing.
• 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.

Sponsors & Collaborators

• Orinove, Inc.: lead
• Vanderbilt University: collaborator

Study Sites (11)

St. Francis Sleep, Allergy & Lung Institute

Clearwater, Florida, 33765, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Avanza Medical Research

Pensacola, Florida, 32503, United States

Location

Coastal Pulmonary and Critical Care

St. Petersburg, Florida, 33704, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

Infinity Medical Research

North Dartmouth, Massachusetts, 02747, United States

Location

Hannibal Clinic

Hannibal, Missouri, 63401, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45220, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Frank Averill, MD

  Sleep, Allergy and Lung Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo-controlled, double blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: November 25, 2020
• Study Start: February 9, 2021
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)