GRI-0621 for Pulmonary Fibrosis

No longer recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GRI-0621, a potential drug for idiopathic pulmonary fibrosis (IPF), a lung condition that causes scarring and breathing problems. The main goal is to determine if taking GRI-0621 daily improves symptoms compared to a placebo, which contains no active drug. A sub-study examines certain immune cells in the lungs. Individuals with long-standing IPF who can breathe without excessive supplemental oxygen might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that GRI-0621 is likely to be safe for humans?

Research has shown that GRI-0621 is safe and well-tolerated in people so far. In studies, the first 24 patients who took GRI-0621 for six weeks did not experience any safety issues. The data also showed no decrease in lung function during this time, indicating that the treatment does not harm the lungs. This is crucial for patients with lung conditions like idiopathic pulmonary fibrosis (IPF). Overall, the evidence supports that GRI-0621 is safe for use in these short-term studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Unlike the standard treatments for pulmonary fibrosis, which often focus on reducing inflammation or slowing disease progression, GRI-0621 offers a novel approach by utilizing tazarotene, a retinoid. This active ingredient is traditionally used in dermatology but is now being explored for its potential to target specific pathways involved in fibrosis. Researchers are excited about GRI-0621 because it may provide a new way to modify the disease process itself, rather than just managing symptoms. Additionally, its once-daily oral administration makes it a convenient option for patients.

What evidence suggests that GRI-0621 might be an effective treatment for pulmonary fibrosis?

Research shows that GRI-0621, which participants in this trial may receive, may help treat idiopathic pulmonary fibrosis (IPF), a lung disease. In earlier studies, patients experienced a positive trend in reducing lung scarring, a major issue in IPF. After six weeks, lung function did not decline, suggesting the treatment might help maintain lung health. Patients also tolerated the treatment well, and it was safe. Early results from biological markers, which indicate disease presence, support its potential to reduce scarring. These findings are promising for those considering joining a trial for this treatment. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1.

gribio.com

gribio.com/gri-bio-reports-6-week-interim-lung-function-data-in-ongoing-phase-2a-study-in-idiopathic-pulmonary-fibrosis-ipf/

GRI Bio Reports 6-Week Interim Lung Function Data ...

No decline in lung function observed at 6-week interim analysis builds upon positive safety and biomarker data.

2.

gribio.com

gribio.com/gri-bios-gri-0621-demonstrates-encouraging-safety-results-at-planned-interim-6-week-analysis-in-ongoing-phase-2a-study-in-idiopathic-pulmonary-fibrosis-ipf/

GRI Bio's GRI-0621 Demonstrates Encouraging Safety ...

Interim results to date demonstrate GRI-0621 to be safe and well-tolerated in the first 24 patients evaluated 6-week interim biomarker data.

3.

pulmonaryfibrosisnews.com

pulmonaryfibrosisnews.com/news/oral-therapy-gri-0621-encouraging-safety-results-ipf-interim-analysis/

Oral therapy GRI-0621 found safe in IPF clinical trial's ...

The initial two-week analysis indicated the therapy is reducing fibrosis as expected. An interim analysis of six-week biomarker data is ongoing, ...

4.

drug-dev.com

drug-dev.com/gri-bios-interim-biomarker-data-demonstrate-positive-trend-toward-anti-fibrotic-effect-of-gri-0621-in-first-12-patients-of-ongoing-phase-2a-study-in-idiopathic-pulmonary-fibrosis/

GRI Bio's Interim Biomarker Data Demonstrate Positive ...

GRI Bio's Interim Biomarker Data Demonstrate Positive Trend Toward Anti-Fibrotic Effect of GRI-0621 in First 12 Patients of Ongoing Phase 2a Study in Idiopathic ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06331624

NCT06331624 | Biomarker Modulation and the Inhibition of ...

Effect of GRI-0621 on pulmonary function (FEV1, FVC, and FEV1/FVC ratio) at baseline and after 6 weeks and 12 weeks of treatment. 6 Weeks and 12 Weeks ...

6.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/gri-bio-gri-0621/

GRI Bio reports interim safety outcomes from GRI-0621 trial ...

GRI Bio CEO Marc Hertz said: “We are happy to report the IDMC confirmed no safety concerns in the first 24 subjects evaluated after six-weeks ...