GRI-0621 for Pulmonary Fibrosis

Recruiting in Palo Alto (17 mi)

+17 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: GRI Bio Operations, Inc.

Must not be taking: CYP2C8 inhibitors, CYP2C8 inducers

Disqualifiers: Emphysema, Coronary artery disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that if you are already on approved IPF therapies, you must stay on your current medication from the start of the trial until the last study visit. However, you cannot start any new IPF therapies or take oral corticosteroids over 10 mg/day within 4 weeks of the trial's start.

How does the drug GRI-0621 differ from other treatments for pulmonary fibrosis?

The drug GRI-0621 is unique because it may target specific pathways involved in pulmonary fibrosis, potentially offering a novel approach compared to existing treatments that primarily slow disease progression. While other treatments like pirfenidone are antifibrotic agents, GRI-0621 might work through different mechanisms, possibly providing a new option for patients.

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Eligibility Criteria

This trial is for people with Idiopathic Pulmonary Fibrosis (IPF), a type of lung scarring. Participants should be diagnosed with IPF to qualify. The summary provided does not include specific inclusion or exclusion criteria, so additional details such as age, disease severity, and other health requirements are unknown.

Inclusion Criteria

Life expectancy of at least 12 months

I am willing and able to sign a consent form for the study.

FEV1/FVC ratio > 0.65 within 4 weeks of Screening

Exclusion Criteria

I have had a sudden worsening of my lung condition in the last 6 months.

I haven't had a heart attack or unstable chest pain in the last 6 months.

My recent lung scan shows more emphysema than fibrosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GRI-0621 or placebo once daily for 12 weeks

12 weeks

Weekly visits for safety and efficacy assessments

Sub-Study

Examination of NKT cell activity in BAL fluid for up to 12 eligible subjects

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests the effects of an oral drug called GRI-0621 versus a placebo in patients with IPF. It's a double-blind study, meaning neither the researchers nor participants know who gets the real drug or placebo. The treatment lasts for 12 weeks and includes monitoring natural killer T (NKT) cells in some subjects.

Group I: Placebo Experimental Treatment 1 Intervention

Placebo 4.5mg, administered orally once daily (QD)

Group II: GRI-0621 Experimental Treatment 1 Intervention

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Phoenix, AZ

Montefiore Medical Center Bronx, NY

Newport Native MD, Inc. Newport Beach, CA

Southeastern Research Center Winston-Salem, NC

More Trial Locations

Who Is Running the Clinical Trial?

GRI Bio Operations, Inc. Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

RS4651 suppresses lung fibroblast activation via the TGF-β1/SMAD signalling pathway. [2021] Idiopathic pulmonary fibrosis (IPF) is a progressive disease resulting in respiratory failure with no efficient treatment options. We investigated the protective effect of RS4651 on pulmonary fibrosis in mice and the mechanism.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels. [2020] Background: Antifibrotic agents have been approved for the treatment of idiopathic pulmonary fibrosis (IPF). However, the efficacy of these drugs in the treatment of familial IPF (FIPF) has not been previously reported. Case presentation: We report the case of a 77-year-old man with FIPF, successfully treated with pirfenidone. His uncle died due to IPF, and his niece was diagnosed with the disease. He had worsening dyspnea two months prior to admission to our hospital. Upon admission, he had desaturation when exercising and broad interstitial pneumonia. Administration of pirfenidone improved his dyspnea, desaturation, and the reticular shadow on his chest radiograph. Increased fibrotic marker levels KL-6 and SP-D were also normalized in six months; treatment had no effect on his serum periostin level. Pirfenidone has been effective for over two years. Conclusion: Antifibrotic agents such as pirfenidone may be useful for the management of FIPF, as well as cases of sporadic IPF.

3. Germany pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants. [2018] Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants.

4. United States pubmed.ncbi.nlm.nih.gov

Targeted inhibition of PI3 kinase/mTOR specifically in fibrotic lung fibroblasts suppresses pulmonary fibrosis in experimental models. [2022] Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an average life expectancy of 3 to 5 years. IPF is characterized by progressive stiffening of the lung parenchyma due to excessive deposition of collagen, leading to gradual failure of gas exchange. Although two therapeutic agents have been approved from the FDA for IPF, they only slow disease progression with little impact on outcome. To develop a more effective therapy, we have exploited the fact that collagen-producing myofibroblasts express a membrane-spanning protein, fibroblast activation protein (FAP), that exhibits limited if any expression on other cell types. Because collagen-producing myofibroblasts are only found in fibrotic tissues, solid tumors, and healing wounds, FAP constitutes an excellent marker for targeted delivery of drugs to tissues undergoing pathologic fibrosis. We demonstrate here that a low-molecular weight FAP ligand can be used to deliver imaging and therapeutic agents selectively to FAP-expressing cells. Because induction of collagen synthesis is associated with phosphatidylinositol 3-kinase (PI3K) activation, we designed a FAP-targeted PI3K inhibitor that selectively targets FAP-expressing human IPF lung fibroblasts and potently inhibited collagen synthesis. Moreover, we showed that administration of the inhibitor in a mouse model of IPF inhibited PI3K activation in fibrotic lungs, suppressed production of hydroxyproline (major building block of collagen), reduced collagen deposition, and increased mouse survival. Collectively, these studies suggest that a FAP-targeted PI3K inhibitor might be promising for treating IPF.

5. England pubmed.ncbi.nlm.nih.gov

Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. [2018] Pulmonary fibrosis (PF) leads to progressive and often irreversible loss of lung functions, posing a health threat with no effective cure. We examined P-Rex1, a PI3K- and G protein βγ-regulated guanine nucleotide exchange factor (GEF) of the Rac small GTPase, for its potential involvement in PF. In a bleomycin-induced PF model, mice deficient in p-rex1 had well-preserved alveolar structure and survived significantly better than their wild type (WT) littermates. The p-rex1(-/-) mice expressed significantly less proinflammatory cytokines and chemokines and had reduced leukocyte infiltration in the lung tissue than their WT littermates. P-Rex1 was detected in lung fibroblasts of WT mice, and its genetic deletion attenuated TGFβ-1-stimulated lung fibroblast migration, Rac1 activation and p38 MAPK phosphorylation. The p-rex1(-/-) mice showed significantly reduced pathological changes including the expression of α-smooth muscle actin, fibronectin and TGFβ-1 compared with their WT controls. Expression of a GEF-deficient P-Rex1 mutant effectively blocked Smads-dependent transcriptional activation, suggesting that P-Rex1 is a downstream mediator of TGFβ-1 signaling. These findings identify P-Rex1 as a novel player of PF, suggesting that targeting P-Rex1 may simultaneously block the inflammatory and fibrogenic processes of PF.