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.
12345Eligibility 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.
+4 more
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.
+7 more
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: TTI-101 800 mg/dayExperimental Treatment1 Intervention
Participants will receive 800 mg/day of TTI-101 BID for 12 weeks.
Group II: TTI-101 400 mg/dayExperimental Treatment1 Intervention
Participants will receive 400 mg/day of TTI-101 twice daily (BID) for 12 weeks.
Group III: PlaceboPlacebo Group1 Intervention
Participants will receive a matching placebo BID for 12 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California Irvine (UCI) HealthOrange, CA
University of FloridaGainesville, FL
UHealth - University of Miami Health SystemsMiami, FL
Loyola University Medical CenterMaywood, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Tvardi Therapeutics, IncorporatedLead Sponsor
References
[Treatment of pulmonary fibrosis. New substances and new interventions]. [2021]Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor prognosis. The IFIGENIA trial showed that antioxidative therapy with N-acetylcysteine versus placebo for patients under treatment with prednisone plus azathioprine significantly slowed the deterioration of pulmonary function after 12 months. A number of other drugs have recently been evaluated in large multicenter placebo-controlled trials. Etanercept, interferon-γ, bosentan, ambrisentan, imatinib, and sildenafil did not show efficacy. The antifibrotic active ingredient pirfenidone is the first drug approved for the treatment of adult patients with mild to moderate idiopathic pulmonary fibrosis in the European Union. Approval was based on the results of 4 randomized, placebo-controlled clinical trials including more than 1,100 patients. Pirfenidone slowed the decline in lung function and reduced the risk of disease progression. Side effects include gastrointestinal discomfort, skin reactions, including photosensitivity, and rarely increased liver enzymes.
External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. [2023]Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown. Objectives: To develop IPF ECs by fit-for-purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the phase II RCT of BMS-986020. Methods: After data curation, the rate of change in FVC from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed-effects models with inverse probability weights. Measurements and Main Results: At 26 weeks, the rates of change in FVC were -32.71 ml for BMS-986020 and -130.09 ml for BMS-placebo (difference, 97.4 ml; 95% confidence interval [CI], 24.6-170.2), replicating the original BMS-986020 RCT. RCT ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Pulmonary Fibrosis Foundation Patient Registry ECs and EHR ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment-effect point estimates outside of the 95% CI of the original BMS-986020 RCT. Conclusions: IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, whereas ECs from real-world data sources, including registry or EHR data, do not. RCT ECs may serve as a potentially useful supplement to future IPF RCTs.
Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. [2022]Approximately 12-13% of patients with interstitial lung disease (ILD) are diagnosed with unclassifiable ILD (uILD), often despite thorough evaluation. A recent Phase 2 study (NCT03099187) described a significant effect of pirfenidone vs. placebo on forced vital capacity (FVC) measured by site spirometry in patients with progressive fibrosing uILD (hereafter referred to as the pirfenidone in uILD study). Here, we present the results from a post-hoc analysis of this study to assess patient baseline characteristics and the efficacy of pirfenidone vs. placebo analyzed by surgical lung biopsy (SLB) status. Mean FVC (mL) change over 24 weeks was included as a post-hoc efficacy outcome. Of 253 randomized patients, 88 (34.8%) had a SLB and 165 (65.2%) did not. Baseline characteristics were generally similar between SLB subgroups; however, patients who had a SLB were slightly younger and had a higher 6-min walk distance than those without a SLB. Mean FVC change over 24 weeks for pirfenidone vs. placebo was -90.9 vs. -146.3 mL, respectively, in patients who had a SLB, and 8.2 vs. -85.3 mL, respectively, in patients without a SLB. Overall, the results from the post-hoc analysis identified that pirfenidone may be an effective treatment in progressive fibrosing uILD over 24 weeks, irrespective of SLB status; however, caution should be taken when interpreting these data due to several limitations. There are differences in the treatment effect of pirfenidone between the subgroups that require further pathological and radiological investigation. In this manuscript, we also descriptively compared baseline characteristics from the overall pirfenidone in uILD study population with other uILD populations reported in the literature, with the aim of understanding if there are any similarities or differences within these cohorts. Most baseline characteristics for patients in the pirfenidone in uILD study were within the ranges reported in the literature; however, ranges were wide, highlighting the heterogeneity of uILD populations.
Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis. [2023]Label="WHAT IS THIS SUMMARY ABOUT?" NlmCategory="UNASSIGNED">This plain language summary describes the main findings from a trial in people with idiopathic pulmonary fibrosis (also called IPF) that was recently published in the New England Journal of Medicine. IPF is a rare disease, where the lungs become more and more scarred, with breathing and oxygen uptake becoming increasingly difficult. This trial looked at the medication BI 1015550 as a potential treatment for IPF. It compared BI 1015550 to placebo (a dummy drug that does not contain any active ingredients) to investigate the effectiveness of the drug in treating people with IPF. The study also looked at the additional medical issues (referred to as adverse events) reported during the study. Some participants took approved treatments to reduce scarring (nintedanib or pirfenidone), and some did not.
[Drug treatments for idiopathic pulmonary fibrosis]. [2019]Idiopathic pulmonary fibrosis is a disease of unknown cause characterized by cough, progressive dyspnea, restrictive respiratory disorder, a typical honeycomb aspect on the high-resolution CT-scan, and usual interstitial pneumonia at histological examination of the lung biopsy. Most patients die 3 to 8 years after diagnosis. Current treatment is based on a combination of corticosteroids and immunosuppressants, but the efficacy of treatment remains a matter of debate. New therapeutics currently under evaluation in controlled clinical trials include interferon-gamma, pirfenidone, N-acetylcysteine, etanercept (anti-TNFalpha), bosentan (endothelin receptor antagonist), imatinib (tyrosine-kinases inhibitor of the PDGF receptor), etc. At the same time, new compounds showing efficacy in experimental models of fibrosis and the development of new pathophysiological concepts open new perspectives both in terms of concept and clinical practice.