TVD-101-003P: A Phase 2 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TTI-101 in Participants with Idiopathic Pulmonary Fibrosis (TVARDI)

The purpose of this research is to compare the effects, good or bad, of the investigational drug TTI-101 versus placebo in people with idiopathic pulmonary fibrosis (IPF). This research will also assess the effect of TTI-101 on lung function.

For more information, visit https://classic.clinicaltrials.gov/ct2/show/NCT05671835

Inova Fairfax Medical Campus
3300 Gallows Road
Falls Church, VA  22042

The participant and the treating physician should have considered all medicinal treatment options and/or possibly lung transplantation prior to considering participation in the study. Participants must meet all the following criteria to be eligible:

PLEASE SEE SELECT CRITERIA
 

1. Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
2.  Age ≥40 years at the time of informed consent.
3. Diagnosed with IPF based on either the 2018 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) International Diagnostic Guidelines or on the 2022 updated Guidelines within 7 years prior to the date of informed consent. If a lung biopsy was required to make the diagnosis of IPF per the 2018 or 2022 ATS/ERS/JRS/ALAT International Diagnostic Guidelines, then that biopsy must have been a surgical lung biopsy or a transbronchial lung cryobiopsy and performed within 7 years of screening in order to fulfill inclusion criteria #3.
4. Chest HRCT performed within 12 months prior to providing informed consent meeting requirements for IPF diagnosis based on the 2018 or 2022 ATS/ERS/JRS/ALAT guidelines and confirmed by central review. If a subject did not have a chest HRCT that was performed within 12 months of informed consent, then they will be required to have a chest HRCT performed during screening for central review. If the HRCT pattern demonstrates a Usual Interstitial Pneumonia (UIP) or probable UIP pattern by central read, the PI's diagnosis of IPF in appropriate clinical context is sufficient without a lung biopsy. If the HRCT pattern is indeterminant for UIP or consistent with an alternative diagnosis, then a historical surgical lung biopsy or transbronchial lung cryobiopsy demonstrating UIP on histopathology is required to confirm the diagnosis of IPF in the appropriate clinical context. 
5. The total extent of fibrotic changes are greater than the extent of emphysematous changes on the HRCT being utilized for IPF diagnosis confirmation.
6. Greater than 40% of predicted FVC and a ratio of forced expiratory volume in 1 second (FEV1)/FVC ≥0.7 measured pre-bronchodilator during screening confirmed by central review.
7. A predicted DLCO (hemoglobin [Hb] corrected) >25% during screening confirmed by central review.
8. SpO2 ≥88% with up to 4L O2/min by pulse oximetry at rest.
9. If currently receiving nintedanib, dose must have been stable for >3 months prior to randomization. If participant has previously discontinued nintedanib, there is a 6-week washout period required before screening can begin.
10. Has a life expectancy of at least 12 months.
11. Able to comply with the requirements of the study protocol, according to the investigator's best judgment.

Participants meeting any of the following exclusion criteria will not be eligible:

PLEASE SEE SELECT CRITERIA

1. Pregnant or breastfeeding
2. Known to have the following diseases at screening (in case of relevant disease suspicion of any of the below, confirmatory tests should be performed to rule out any of the following conditions):

• Uncontrolled pulmonary hypertension, or pulmonary hypertension requiring chronic medical treatment (eg, sildenafil, bosentan)
• Congestive heart failure - New York Heart Association Class III or IV
• Diffuse panbronchiolitis
• Pulmonary tuberculosis
• Bronchiectasis from non-IPF causes (recurrent infections, Cystic fibrosis, Primary Ciliary Dyskinesia, chronic MAI infection, and immunoglobulin deficiencies). This does not include the imaging finding of traction bronchiectasis in the setting of IPF.
• Pulmonary mycosis
• Respiratory infection (viral pneumonia, bacterial pneumonia, mycoplasmal pneumonia, etc). Patient may be rescreened 4 weeks after full recovery.
• Drug-induced interstitial pneumonia, pneumoconiosis, hypersensitivity pneumonitis, or radiation pneumonitis
• Collagen vascular disease with involvement of the lung, autoimmune disease with involvement of the lung, sarcoidosis, granulomatous disease, vasculitis, eosinophilic pneumonia, acute lung injury of known origin, cancerous lymphangiopathy, alveolar epithelial carcinoma, pulmonary lymphangioleiomyomatosis, alveolar proteinosis, Langerhans cell granulomatosis, pneumocystis pneumonia, cytomegalovirus pneumonia
• Severe hypertension (may not participate if BP is ≥160/100 mmHg despite maximal therapy) within 3 months of Visit 1
• Myocardial infarction, unstable cardiac angina, or history of thrombotic event (including stroke and transient ischemic attack) within 6 months of screening
• History of significant/symptomatic bradycardia long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome or any of the following:
  • Known risk of prolonged QT interval or Torsades de Pointes.
  • Uncorrected hypomagnesemia or hypokalemia.
  • Systolic blood pressure >160 mmHg or <90 mmHg.
  • Bradycardia (heart rate <50 bpm at rest) by electrocardiogram (ECG) or pulse.
• Corrected QT interval (QTc) using Fridericia's correction (QTcF) >450 msec for men and >470 msec for women at screening.

3. Unresolved respiratory tract infection within 4 weeks (including COVID-19 infections) or an acute exacerbation of IPF within 3 months prior to screening