Evaluation of Efficacy, Tolerability, Safety, and Dose Response of Deupirfenidone (LYT-100) in Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-511330-13-00
- Protocol
- LYT-100-2022-204
- Sponsor
- Puretech Lyt 100 Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to obtain clinical data establishing the **safety**, **tolerability**, **efficacy**, and dosing regimen of LYT-100 in patients with **Idiopathic Pulmonary Fibrosis** (IPF). This is clinically relevant as it aims to provide comprehensive insights into the therapeutic potential and optimal dosing of LYT-100, which could significantly impact the management and treatment outcomes for patients with IPF.
Secondary objectives include:
- Assessing the safety and tolerability of long-term treatment with LYT-100 in the IPF population.
- Comparing the rate of change in Forced Vital Capacity (FVC) through the end of Part B Period 1 to that observed during Part A, by Part A treatment group assignment and by Part B LYT-100 target dose.
Participants
The clinical trial involves a total of **226 participants** diagnosed with **Idiopathic Pulmonary Fibrosis** (IPF). The study population includes both male and female subjects, aged **40 years and older**, who are either treatment-naïve or have less than six months of exposure to nintedanib. Participants were selected based on specific criteria, including a physician-diagnosed IPF according to the 2018 guidelines by the American Thoracic Society and other relevant societies. The trial population is required to have a diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin between 30% and 90% of predicted normal, and a forced vital capacity (FVC) of at least 45% of predicted normal. Lifestyle considerations such as diet and physical activity are not specified, but participants must be able to perform and comply with all study procedures. The trial includes a vulnerable population, and both male and female participants must adhere to strict contraceptive measures to prevent pregnancy during and after the study period.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, four-arm study to evaluate the efficacy, tolerability, safety, and dose response of LYT-100 in patients with **Idiopathic Pulmonary Fibrosis** (IPF). The trial includes both active and placebo-controlled groups and is structured to provide comprehensive data on the investigational product, Deupirfenidone (LYT-100), administered in tablet and capsule forms. The trial is divided into two parts, with Part A spanning 26 weeks and Part B extending the study to a total of 52 weeks. The primary objective is to assess the rate of decline in forced vital capacity (FVC) over the initial 26 weeks, with secondary endpoints including time to IPF progression, hospitalization rates, and changes in quality of life measures.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and previous treatment history. Following successful screening, participants will be randomized into one of the four study arms. Regular follow-up visits will occur throughout the trial to monitor safety, efficacy, and adherence to the study protocol. These visits will include assessments such as spirometry, high-resolution computed tomography (HRCT), and quality of life questionnaires. The end-of-study visit will conclude the participant's involvement, with a final evaluation of all study parameters.
The expected duration of participant involvement is up to 52 weeks, contingent upon the completion of both parts of the study. Conditions that may lead to early termination from the study include adverse events, non-compliance with study procedures, or withdrawal of consent. Participants are required to adhere to specific contraceptive measures and are advised against sperm donation for a specified period post-study. The trial aims to provide robust data to inform the safety and efficacy profile of LYT-100 in the treatment of IPF, contributing to the understanding of its potential therapeutic benefits.
Treatment
The clinical trial involves the administration of **Deupirfenidone (LYT-100)**, which is provided in two pharmaceutical forms: tablets and capsules. The active substance, deupirfenidone, is a chemically derived compound. The maximum daily dose for deupirfenidone is 2475 mg, with a total maximum dose of 450.45 g over a treatment period of 26 weeks. The medication is administered orally. The trial aims to evaluate the efficacy, tolerability, safety, and dose response of LYT-100 in patients with **Idiopathic Pulmonary Fibrosis (IPF)**.
**Pirfenidone** is used as a comparator treatment in the study. It is provided in the form of film-coated tablets, with the active substance being pirfenidone. The maximum daily dose for pirfenidone is 2403 mg, with a total maximum dose of 437.34 g over the same 26-week treatment period. Pirfenidone is also administered orally. For the purpose of blinding, the tablets are over-encapsulated and labeled specifically for the clinical trial.
A **placebo** is included in the trial to match the appearance of both LYT-100 and pirfenidone capsules. The placebo is designed to ensure the double-blind nature of the study, allowing for an unbiased comparison of the effects of the active treatments against a non-active control. The placebo is administered orally, following the same schedule as the active treatments.
Efficacy
The efficacy of the investigational product, **Deupirfenidone (LYT-100)**, in patients with **Idiopathic Pulmonary Fibrosis (IPF)** will be assessed through a series of primary and secondary endpoints over the course of the clinical trial. The primary endpoint is the rate of decline in Forced Vital Capacity (FVC) measured in milliliters over Part A of the trial, which spans 26 weeks. Secondary endpoints include the rate of decline in FVC percentage predicted (FVCpp) over the same period, time to IPF progression, time to hospitalization due to respiratory causes, and all-cause mortality through 26 weeks. Additional secondary endpoints involve changes from baseline to Week 26 in quality of life questionnaires such as the King's Brief Interstitial Lung Disease Questionnaire (K-BILD), St. George’s Respiratory Questionnaire – IPF Version (SGRQ-I), and the EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D). Changes in serum biomarkers and the number and duration of respiratory hospitalizations or pulmonary exacerbations will also be evaluated.
Measurements will be collected at specified timepoints, including baseline, Week 26, and for Part B, from Week 26 to Week 52. Spirometry assessments will be utilized to obtain FVC values, while patient-reported outcomes will be gathered using validated questionnaires. The analysis will focus on the comparison of these parameters between the treatment and placebo groups to determine the efficacy of Deupirfenidone (LYT-100) in slowing disease progression and improving patient outcomes in IPF.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written or electronic informed consent from the participant prior to any study procedures in a manner approved by an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Human Research Ethics Committee (HREC)
- Male or female, age of ≥40 years at the time of informed consent
- Able to perform and willing to comply with all study procedures and requirements
- Treatment-naïve patients or those with <6 months of exposure to nintedanib with physician-diagnosed IPF based on American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) 2018 guidelines
- IPF on high-resolution computed tomography (HRCT), performed within 12 months of Visit 1 as confirmed by central readers
- The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan as determined by the investigator and the central reader
- Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin (Hb) [Visit 1] ≥30% and ≤90% of predicted normal where available at the study site.
- FVC ≥45% of predicted normal
- Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must be abstinent from heterosexual intercourse throughout the study and for 30 days following last dose of study medication or agree to use 1 of the acceptable, highly effective methods of double contraception which is defined as male use of a condom AND 1 form of the following: a. oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation b. oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation c. intrauterine device (IUD)
- Male participants must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent, or, if engaged in heterosexual relations, any female partner must be postmenopausal, surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or using an acceptable, highly effective contraceptive method from Screening until study completion, including the follow-up period and for no less than 90 days (males) and 30 days (females) after the last dose of study medication along with the use of male condom
- Males will not donate sperm for at least 90 days after the last dose of study medication
- Female partners of male participants and female participants will report pregnancy occurring within 30 days from cessation of study medication
- Part B: Signed informed consent for Part B prior to any study-mandated procedures
- Part B: Participant must have completed Part A of the study through Day 183 of treatment
- Part B: In the opinion of the investigator, the participant is a good candidate for continued treatment
Exclusion Criteria
- Participants who, in the judgement of the investigator, are unlikely to be able to fulfill study participation requirements
- Use of any of the following drugs within 2 weeks prior to Visit 2/baseline or planned during the duration of the study: a. Strong and moderate CYP1A2 inhibitors (ie, ciprofloxacin, fluvoxamine, enoxacin, methoxsalen, mexiletine, vemurafenib) and phenytoin, rifampin, and terifluonmide (inducers of CYP1A2) b. Medications associated with substantial risk for prolongation of the QTc interval including but not limited to moxifloxacin, quinidine, procainamide, sotalol, amiodarone (discontinued at least 90 days from V2) c. Immunosuppressant medications such as azathioprine, cyclophosphamide, cyclosporin A, metho-trexate, prednisone at a steady dose >10mg/day or equivalent (Prednisone should be at a stable dose for at least 90 days prior to V2). d. Medications used to treat PH such as endothelin receptor antagonists (eg, ambrisentan, bosentan, and macitentan), phosphodiesterase-5 inhibitors (sildenafil and tadalafil used to treat erectile dys-function are allowed), guanylate cyclase stimulators (eg, riociguat), prostacyclin analogs (eg, epo-prostenol, treprostnil, iloprost), or prostacyclin receptor agonists (eg, selexipag) e. Warfarin, as it may worsen IPF f. Vaccination with a live vaccine is not permitted during the period from 4 weeks prior to Screening to 4 weeks after the last dose. The medical monitor should be consulted if there is any question about a particular vaccine.
- Significant clinical worsening (as per Investigator’s discretion) of IPF between Screening and Baseline Visits
- A current immunosuppressive condition (eg, HIV)
- Active alcohol or drug abuse
- Use of smoked (burnt) tobacco products or vaping/e-cigarettes
- Other disease (including malignancy) that may interfere with testing procedures or in the judgement of the investigator may interfere with study participation or may put the participant at risk when participating in this study
- Participants with a documented hypersensitivity to LYT-100
- Participants with a documented lactose or galactose intolerance
- Part B: Participants must not meet any exclusion criteria listed for Part A
- Part B: Participants who discontinued study medication and started receiving commercially available antifibrotic medication during Part A will not be eligible for Part B
- Primary obstructive airway physiology (pre-bronchodilator forced expiratory volume in the first second [FEV1]/FVC <0.7 at Visit 1)
- Part B: Participants whose treatment assignment is unblinded during Part A will not be eligible for Part B
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) at Visit 1
- Part B: Any known factor or disease that interferes with treatment compliance, study conduct, or interpretation of the results, as judged by the investigator
- Total bilirubin >1.5 × ULN at Visit 1. Exceptions may be made on a case-by-case basis for participants with Gilbert’s syndrome in consultation with the medical monitor
- Creatinine clearance <30 mL/min calculated by Cockcroft–Gault formula at Visit 1 [Note: Laboratory parameters from Visit 1 will be used to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results may be available only after randomization. If the Visit 2 results no longer satisfy the entry criteria, the investigator will determine whether it is justified that the participant remains on study drug. The justification for this decision needs to be documented.]
- Participants with underlying chronic liver disease (Child-Pugh B or C hepatic impairment)
- Current or prior treatment with pirfenidone
- Other investigational therapy received within 1 month prior to randomization (Visit 2)
- Significant pulmonary hypertension (PH) defined by any of the following: a. Previous clinical or echocardiographic evidence of significant right heart failure b. History of right heart catheterization showing a cardiac index ≤2 L/min/m² c. PH requiring inhaled, subcutaneous, or intravenous therapy with epoprostenol/treprostinil d. In the principal investigator's opinion, the study participant’s symptoms are more related to their PH than to their IPF
- Known explanation for interstitial lung disease, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer
- Major surgical procedures during Screening or study periods, with the exception of pre-planned procedures that will not interfere with study participation
- Diagnosis of any connective tissue disease, including but not limited to scleroderma/systemic sclerosis, Sjogren’s disease, mixed connective tissue diseases, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
- In the opinion of the investigator, other clinically significant pulmonary abnormalities, including prior or current lung cancer (treated within the past 5 years)
- Major extrapulmonary physiological restriction (eg, chest wall abnormality, large pleural effusion)
- Cardiovascular diseases, any of the following: a. Uncontrolled hypertension, within 3 months of Visit 1 b. Myocardial infarction within 6 months of Visit 1 c. Unstable cardiac angina within 6 months of Visit 1
- Prior hospitalization within 3 months prior to Visit 1 for confirmed COVID-19, acute exacerbation of IPF, or any lower respiratory tract infection
- Known symptoms of dysphagia or known difficulty in swallowing capsules or tablets and/or total gastrectomy
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 28 Jan 2023 | 8 |
 Romania | Not Recruiting | 28 Jan 2023 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo to match lyt-100 and pirfenidone capsules | Placebo | N/A | — | — | — | N/A |
PIRFENIDONE | Comparator | — | ORAL | 2403 | 26 | SUB09907MIG |
DeupirfenidoneLYT-100 | Test | TABLET | ORAL | 2475 | 26 | PRD11176048 |
DeupirfenidoneLYT-100 | Test | CAPSULE | ORAL | 2475 | 26 | PRD8262215 |