Biomarker Modulation and the Inhibition of NKT1 Cells by Oral GRI-0621 in Patients With IPF

NCT06331624 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: GRI-0621-IPF-02
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 16

Brief Summary

This is a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study. Approximately 36 subjects with IPF will be randomized in a 2:1 ratio for GRI-0621 4.5mg or Placebo. GRI-0621 dose of 4.5mg will be compared with placebo following once daily oral administration for 12 weeks. Concurrently, a Sub-Study will be conducted, examining the number and activity of NKT cells in BAL, for up to 12 eligible subjects (across various centers). An early-stage patient variability assessment will be completed when 12 subjects have completed 2 weeks of treatment. Followed by an interim analysis performed when 24 subjects complete 6 weeks of treatment.

Conditions

Idiopathic Pulmonary Fibrosis; IPF

Keywords

Idiopathic Pulmonary Fibrosis; IPF; Biomarker Modulation; Inhibition of Natural Killer Type 1 (NKT1) Cells; NKT Cells; GRI-0621; Tazarotene

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of oral GRI-0621

  General overall safety and tolerability of oral GRI-0621 as compared to placebo will be assessed by evaluating the following safety parameters: * Adverse events (occurrence and type) * Clinical Laboratory Measurements (normal/abnormal) * Vital signs (normal/abnormal)

  12 Weeks

Secondary Outcomes (4)

• Change from baseline biomarkers

  12 Weeks

• Plasma concentrations of GRI-0621

  12 Weeks

• Pharmacodynamics of GRI-0621 in blood (Study Population)

  6 Weeks and 12 Weeks

• Pharmacodynamics of GRI-0621 in BAL fluid (Optional Sub-Study)

  12 Weeks

Other Outcomes (1)

• Exploratory - Pulmonary Function

  6 Weeks and 12 Weeks

Study Arms (2)

GRI-0621

EXPERIMENTAL

GRI-0621 (tazarotene) 4.5mg, administered orally once daily (QD)

Drug: Tazarotene (GRI-0621)

Placebo

EXPERIMENTAL

Placebo 4.5mg, administered orally once daily (QD)

Drug: Placebo

Interventions

Tazarotene (GRI-0621) DRUG

Oral 4.5mg soft gel capsule

GRI-0621

Placebo DRUG

Oral 4.5mg soft gel capsule

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects 40 through 85 years of age, inclusive.
• Confirmed diagnosis of IPF with clinical features consistent with the current clinical practice guidelines for IPF.
• FVC \> 50% predicted value within 4 weeks of Screening.
• FEV1/FVC ratio \> 0.65 within 4 weeks of Screening.
• Diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOc) \> 30%predicted value within 4 weeks of Screening.
• Life expectancy of at least 12 months.
• Willing and able to follow the study required visits and assessments. For Sub-Study subjects, willing and able to undergo BAL procedures at Screening and at Week 12.
• Willing and able to provide written informed consent prior to study-related procedures.

You may not qualify if:

• Initiation of any approved or investigational IPF therapy or oral corticosteroids (\> 10 mg/day) within 4 weeks of Screening. Subjects already on approved IPF therapies must remain on their current medication from Screening until the last study visit.
• High resolution computerized tomography (HRCT) pattern showing emphysema more than the extent of fibrosis of the lung area within 12 months of Screening.
• Acute exacerbation of IPF within 6 months of Screening (Collard et al., 2016).
• Requiring supplemental O2 \> 4 liters/min to maintain peripheral arterial O2 saturation (SpO2) \> 88% at rest. O2 saturation at screening or baseline that is \< 88% at rest.
• Any condition with unacceptable risk for bronchoscopy (for Sub-Study subjects only).
• Current or recent history of clinically significant medical condition, laboratory abnormality, or illness that could place the subject at risk or compromise the quality of the study data as determined by the Investigator.
• Significant coronary artery disease (i.e., myocardial infarction within 6 months or unstable angina within 1 month of Screening).
• An upper or lower respiratory tract infection, presence of or suspected emphysema, within 4 weeks of Screening.
• Eye exam indicating night blindness within 6 months of Screening, or at Screening.
• Bone Mineral Density t-score of -4.0 (severe osteoporosis) within 6 months of Screening, or at Screening.
• Screening QT of \>450 for men and \>470 for women.
• History of renal impairment as deemed clinically relevant by the investigator OR eGFR \<60ml/min/1.73m2 within 60 days of Screening and a Screening eGFR of \<60ml/min/1.73m2.
• History of hepatic impairment as deemed clinically relevant by the investigator OR ALT or AST \>2 x ULN OR moderate and severe hepatic impairment as defined using the Child-Pugh scoring system (i.e., Child-Pugh B and C).
• A history of hypertriglyceridemia (documented TG of \>2.0mmol/L at Screening); a history of pancreatitis from any cause; uncontrolled dyslipidemia with LDL-c \>4.9mmol/L and an HDL-c \<1.3 mmol/L for women and \<1.0 for men, despite optimized treatment.
• Use of moderate or strong inhibitors of CYP2C8 (e.g. gemfibrazol, trimethoprim, clopidogrel) or inducers of CYP2C8 (e.g. rifampin) from 7 days or 5 half-lives, whichever is longer, before the first administration of GRI-0621 until cessation of GRI-0621 administration.

Sponsors & Collaborators

• GRI Bio Operations, Inc.: lead

Study Sites (16)

Newport Native MD, Inc.

Newport Beach, California, 92663, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Southeastern Research Center

Winston-Salem, North Carolina, 27103, United States

Location

MUSC Pulmonary Research

Charleston, South Carolina, 29425, United States

Location

The Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Concord General Repatriation Hospital

Concord, New South Wales, 2139, Australia

Location

St. George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Royal Infirmary Edinburgh

Edinburgh, Scotland, EH16 4SA, United Kingdom

Location

University Hospital Birmingham, Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, CB2 0BB, United Kingdom

Location

Royal Devon and University Healthcare NHS Foundation Trust

Exeter, EX2 5DW, United Kingdom

Location

University College London Hospitals

London, London, United Kingdom

Location

Western Health and Social Care Trust (WHSCT)

Londonderry, BT47 6SB, United Kingdom

Location

Norfolk & Norwich University Hospital

Norwich, Norwich, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

tazarotene

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: March 26, 2024
• Study Start: April 24, 2024
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

US (5); AU (3); GB (8)