GRI-0621 for Pulmonary Fibrosis

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GRI Bio Operations, Inc.

Must not be taking: CYP2C8 inhibitors, CYP2C8 inducers

Disqualifiers: Emphysema, Coronary artery disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

36 Participants Needed

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. ^{1 2 3 4 5}

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.

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

Treatment Details

Interventions

• GRI-0621

Trial Overview 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.

Participant Groups

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)

Who Is Running the Clinical Trial?

GRI Bio Operations, Inc.

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

RS4651 demonstrated a protective effect against pulmonary fibrosis in mice, as evidenced by reduced collagen deposition and lower levels of alpha-smooth muscle actin (α-SMA) compared to the control group induced with bleomycin.

The mechanism of action for RS4651 involves the upregulation of the SMAD7 gene, which inhibits the TGF-β1/SMAD signaling pathway, leading to decreased cell proliferation and migration in lung fibroblasts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RS4651 suppresses lung fibroblast activation via the TGF-β1/SMAD signalling pathway. Li, S., Xu, A., Li, Y., et al.[2021]

A 77-year-old man with familial idiopathic pulmonary fibrosis (FIPF) showed significant improvement in symptoms and lung function after being treated with pirfenidone, an antifibrotic agent, for over two years.

This case suggests that pirfenidone may be effective not only for sporadic idiopathic pulmonary fibrosis but also for familial cases, indicating its potential broader applicability in treating different forms of IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels. Koga, Y., Hachisu, Y., Tsurumaki, H., et al.[2020]

GSK3008348, an inhaled drug targeting the αvβ6 integrin, was found to be safe and well tolerated in a phase 1 trial with 29 healthy participants, with no serious adverse events reported.

The pharmacokinetic profile showed that maximum plasma concentrations were reached within 30 minutes, and the drug's exposure was dose proportional at doses up to 3000 mcg, supporting its potential as a treatment for idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants. Maden, CH., Fairman, D., Chalker, M., et al.[2018]

A novel therapy targeting fibroblast activation protein (FAP) has been developed to selectively deliver a PI3K inhibitor to collagen-producing myofibroblasts in idiopathic pulmonary fibrosis (IPF), which could improve treatment outcomes.

In a mouse model of IPF, this FAP-targeted PI3K inhibitor effectively reduced collagen synthesis, decreased collagen deposition, and improved survival rates, suggesting its potential as a promising treatment for this lethal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted inhibition of PI3 kinase/mTOR specifically in fibrotic lung fibroblasts suppresses pulmonary fibrosis in experimental models. Hettiarachchi, SU., Li, YH., Roy, J., et al.[2022]

Mice lacking P-Rex1 showed better survival and preserved lung structure in a bleomycin-induced pulmonary fibrosis model, indicating that P-Rex1 plays a harmful role in the disease.

Targeting P-Rex1 may be a promising strategy to reduce inflammation and fibrosis in pulmonary fibrosis, as its absence led to decreased proinflammatory cytokines and reduced lung fibroblast migration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. Liang, Q., Cheng, N., Zhang, G., et al.[2018]

References

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

RS4651 suppresses lung fibroblast activation via the TGF-β1/SMAD signalling pathway. [2021]

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

Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels. [2020]

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

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants. [2018]

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]

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

Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. [2018]