TTI-101 for Idiopathic Pulmonary Fibrosis

Recruiting in Palo Alto (17 mi)

+29 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Tvardi Therapeutics, Incorporated

Must be taking: Nintedanib

Must not be taking: Steroids, Pirfenidone

Disqualifiers: Respiratory infections, Surgery, Cardiac disorders, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the safety and tolerability of oral daily administration of TTI-101 over a 12-week treatment duration in participants with idiopathic pulmonary fibrosis (IPF).

Will I have to stop taking my current medications?

The trial requires that if you are taking nintedanib, your dose must be stable for at least 3 months before joining. If you have stopped taking nintedanib, you need a 6-week period without it before starting the trial. The protocol does not specify requirements for other medications.

What makes the drug TTI-101 unique for treating idiopathic pulmonary fibrosis?

TTI-101 is unique because it is being investigated as a novel treatment option for idiopathic pulmonary fibrosis, a condition with limited effective therapies. Unlike existing treatments like pirfenidone and nintedanib, which are antifibrotic agents, TTI-101 may offer a different mechanism of action, although specific details about its uniqueness compared to other treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for people with idiopathic pulmonary fibrosis (IPF) who have a life expectancy of at least 12 months, can maintain oxygen levels with minimal support, and have not had significant IPF improvement in the past year. They should be on a stable dose of nintedanib or off it for 6 weeks, and meet certain lung function criteria.

Inclusion Criteria

Has a life expectancy of at least 12 months

Predicted DLCO (Hb corrected) ≥25% during screening confirmed by central review

I had a chest scan within the last year that confirms I have IPF.

Exclusion Criteria

I have taken pirfenidone in the last 3 months.

I do not have any lung diseases that would affect my participation in the study.

I am scheduled for surgery during the study period.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TTI-101 or placebo for 12 weeks to evaluate safety and tolerability

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• TTI-101 (Other)

Trial Overview The study tests TTI-101's safety and tolerability against a placebo over 12 weeks. Participants will take TTI-101 orally every day to see how well they tolerate it and if there are any benefits in treating IPF.

Participant Groups

Group I: TTI-101 800 mg/day Experimental Treatment 1 Intervention

Participants will receive 800 mg/day of TTI-101 BID for 12 weeks.

Group II: TTI-101 400 mg/day Experimental Treatment 1 Intervention

Participants will receive 400 mg/day of TTI-101 twice daily (BID) for 12 weeks.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive a matching placebo BID for 12 weeks.

Who Is Running the Clinical Trial?

Tvardi Therapeutics, Incorporated

Lead Sponsor

Trials

5

Recruited

360+

Findings from Research

The IFIGENIA trial demonstrated that N-acetylcysteine, when used alongside prednisone and azathioprine, significantly slowed the decline in lung function in patients with idiopathic pulmonary fibrosis over 12 months.

Pirfenidone is the first approved antifibrotic drug for idiopathic pulmonary fibrosis in the EU, showing efficacy in slowing lung function decline and reducing disease progression in over 1,100 patients across four clinical trials, though it may cause side effects like gastrointestinal discomfort and skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. Costabel, U., Bonella, F.[2021]

External controls (ECs) derived from historical randomized clinical trials (RCTs) showed comparable treatment effects to the original BMS-986020 trial for idiopathic pulmonary fibrosis (IPF), indicating their potential utility in enhancing trial efficiency.

In contrast, ECs from real-world data sources, such as registries and electronic health records, demonstrated a slower rate of lung function decline compared to the placebo group, suggesting they may not provide reliable comparability for evaluating new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. Swaminathan, AC., Snyder, LD., Hong, H., et al.[2023]

In a Phase 2 study involving 253 patients with unclassifiable interstitial lung disease (uILD), pirfenidone demonstrated a significant improvement in forced vital capacity (FVC) compared to placebo over 24 weeks, regardless of whether patients had undergone surgical lung biopsy (SLB).

Patients with SLB showed a mean FVC change of -90.9 mL with pirfenidone versus -146.3 mL with placebo, while those without SLB had a mean change of 8.2 mL with pirfenidone versus -85.3 mL with placebo, indicating that pirfenidone may be effective across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. Molina-Molina, M., Kreuter, M., Cottin, V., et al.[2022]

In a trial involving 147 participants with idiopathic pulmonary fibrosis (IPF) across 22 countries, the medication BI 1015550 was found to effectively prevent the decline in lung function compared to a placebo.

While BI 1015550 did not lead to a higher rate of severe adverse events compared to placebo, it was associated with more cases of diarrhea, and 13 participants discontinued treatment due to medical issues, indicating the need for further studies to assess its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis. Richeldi, L., Azuma, A., Cottin, V., et al.[2023]

Idiopathic pulmonary fibrosis is a serious lung disease with a poor prognosis, where most patients typically survive only 3 to 8 years after diagnosis, and current treatments involving corticosteroids and immunosuppressants have uncertain efficacy.

New potential therapies, such as interferon-gamma, pirfenidone, and imatinib, are being tested in clinical trials, offering hope for improved treatment options based on recent advancements in understanding the disease's mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug treatments for idiopathic pulmonary fibrosis]. Crestani, B., Marchand-Adam, S., Schneider, S.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. [2021]

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

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Drug treatments for idiopathic pulmonary fibrosis]. [2019]