TTI-101 for Idiopathic Pulmonary Fibrosis

No longer recruiting at 31 trial locations

Overseen By Nicole Goodwin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tvardi Therapeutics, Incorporated

Must be taking: Nintedanib

Must not be taking: Steroids, Pirfenidone

Disqualifiers: Respiratory infections, Surgery, Cardiac disorders, others

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, TTI-101, for individuals with idiopathic pulmonary fibrosis (IPF), a lung disease that makes breathing difficult. The main goal is to determine if taking TTI-101 daily is safe and tolerable over 12 weeks. Participants will receive either TTI-101 or a placebo (a pill with no active medicine) to compare effects. Individuals diagnosed with IPF and stable breathing may be suitable for this study. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TTI-101 has been tested in over 150 people and is generally well-tolerated, meaning most participants did not experience major problems while taking it. Although earlier studies in idiopathic pulmonary fibrosis (IPF) did not clearly demonstrate improvements in safety or lung function, they reported no major safety concerns. This suggests that while the drug may not have enhanced lung function, it remained relatively safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TTI-101 for idiopathic pulmonary fibrosis (IPF) because it offers a fresh approach to treating this condition. Unlike current treatments that usually focus on managing symptoms through anti-fibrotic drugs like nintedanib and pirfenidone, TTI-101 targets and inhibits a specific protein involved in the signaling pathways that drive fibrosis. This unique mechanism of action could potentially slow down or even halt the progression of lung scarring, offering hope for more effective management of IPF. Additionally, TTI-101 is being tested in different dosages, which may help optimize its effectiveness and safety for patients.

What evidence suggests that this trial's treatments could be effective for idiopathic pulmonary fibrosis?

This trial will compare different doses of TTI-101 with a placebo for treating idiopathic pulmonary fibrosis (IPF). Research has shown that TTI-101 did not significantly improve lung function in patients with IPF. In one study, lung function, measured by forced vital capacity (FVC), improved in 41% of patients taking a placebo and up to 44% of those taking TTI-101. Thus, TTI-101 did not outperform the placebo in improving lung function. Additionally, no significant benefits in safety or other outcomes were observed. These findings suggest that, so far, TTI-101 has not demonstrated strong evidence of effectiveness for treating IPF. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TTI-101

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ir.tvarditherapeutics.com ir.tvarditherapeutics.com/news-releases/news-release-details/tvardi-therapeutics-provides-update-preliminary-data-phase-2

Tvardi Therapeutics Provides Update on Preliminary Data ... Tvardi Therapeutics Provides Update on Preliminary Data from Phase 2 REVERT Trial in Idiopathic Pulmonary Fibrosis ; Placebo. TTI-101 – 400mg ; n.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05671835

Study of TTI-101 in Participants With Idiopathic Pulmonary ... 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 ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/news/phase-2-ipf-trial-tti-101-insufficient-benefit/

REVERT Phase 2 IPF Trial of TTI-101 Showed Insufficient ... Results of the study determined no benefit in the safety, pharmacokinetics, and exploratory lung function outcomes for patients with IPF.

4. fiercebiotech.com fiercebiotech.com/biotech/tvardis-stat3-inhibitor-flunks-phase-2-ipf-trial-amid-high-dropout-rates

Tvardi's STAT3 inhibitor flunks IPF trial amid high dropout ... Tvardi said FVC, a measure of lung function, improved in 41% of patients on placebo, compared to up to 44% of people on the study drug. FVC ...

5. pulmonaryfibrosis.org pulmonaryfibrosis.org/patients-caregivers/medical-and-support-resources/clinical-trials-education-center/pipeline/drug/idiopathic-pulmonary-fibrosis/tti-101

TTI-101 Study Purpose. The REVERTIPF clinical trial is evaluating the safety and effectiveness of TTI-101 alone or with nintedanib (OFEV®) in adults with ...

6. journal.chestnet.org journal.chestnet.org/article/S0012-3692(24)04650-6/fulltext

REVERT-IPF STUDY - CHEST Journal To date, TTI-101 has been well tolerated in over 150 subjects and demonstrated direct inhibition of STAT3 activation.As a prelude to the ongoing Phase 2 ...