A Randomized Double-blind Trial to Evaluate the Efficacy, Tolerability, Safety and Dose Response of LYT-100 in Patients with Idiopathic Pulmonary Fibrosis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Puretech Lyt 100 Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

17 Jan 2023 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

PureTech LYT 100, Inc.

External identifiers

EU CT number

2024-511330-13-00

EudraCT number

2021-006820-41

WHO UTN

U1111-1304-7131

ClinicalTrials.gov

NCT05321420

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety, Others

To obtain clinical data establishing the safety, tolerability, efficacy, and dosing regimen of LYT-100 in patients with IPF

Secondary objectives 2

1. Part B: Assess the safety and tolerability of long-term treatment with LYT-100 in the IPF population
2. Part B: Compare the rate of change in 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

Conditions and MedDRA coding

Idiopathic Pulmonary Fibrosis

Study design 8 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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)
2. Male or female, age of ≥40 years at the time of informed consent
3. Able to perform and willing to comply with all study procedures and requirements
4. 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
5. IPF on high-resolution computed tomography (HRCT), performed within 12 months of Visit 1 as confirmed by central readers
6. 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
7. 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.
8. FVC ≥45% of predicted normal
9. 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)
10. 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
11. Males will not donate sperm for at least 90 days after the last dose of study medication
12. Female partners of male participants and female participants will report pregnancy occurring within 30 days from cessation of study medication
13. Part B: Signed informed consent for Part B prior to any study-mandated procedures
14. Part B: Participant must have completed Part A of the study through Day 183 of treatment
15. Part B: In the opinion of the investigator, the participant is a good candidate for continued treatment

Exclusion criteria 29

1. Participants who, in the judgement of the investigator, are unlikely to be able to fulfill study participation requirements
2. 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.
3. Significant clinical worsening (as per Investigator’s discretion) of IPF between Screening and Baseline Visits
4. A current immunosuppressive condition (eg, HIV)
5. Active alcohol or drug abuse
6. Use of smoked (burnt) tobacco products or vaping/e-cigarettes
7. 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
8. Participants with a documented hypersensitivity to LYT-100
9. Participants with a documented lactose or galactose intolerance
10. Part B: Participants must not meet any exclusion criteria listed for Part A
11. Part B: Participants who discontinued study medication and started receiving commercially available antifibrotic medication during Part A will not be eligible for Part B
12. Primary obstructive airway physiology (pre-bronchodilator forced expiratory volume in the first second [FEV1]/FVC <0.7 at Visit 1)
13. Part B: Participants whose treatment assignment is unblinded during Part A will not be eligible for Part B
14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) at Visit 1
15. Part B: Any known factor or disease that interferes with treatment compliance, study conduct, or interpretation of the results, as judged by the investigator
16. 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
17. 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.]
18. Participants with underlying chronic liver disease (Child-Pugh B or C hepatic impairment)
19. Current or prior treatment with pirfenidone
20. Other investigational therapy received within 1 month prior to randomization (Visit 2)
21. 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
22. 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
23. Major surgical procedures during Screening or study periods, with the exception of pre-planned procedures that will not interfere with study participation
24. 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
25. In the opinion of the investigator, other clinically significant pulmonary abnormalities, including prior or current lung cancer (treated within the past 5 years)
26. Major extrapulmonary physiological restriction (eg, chest wall abnormality, large pleural effusion)
27. 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
28. Prior hospitalization within 3 months prior to Visit 1 for confirmed COVID-19, acute exacerbation of IPF, or any lower respiratory tract infection
29. Known symptoms of dysphagia or known difficulty in swallowing capsules or tablets and/or total gastrectomy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of decline in FVC (in mL) over Part A (26 weeks)

Secondary endpoints 22

1. Rate of decline in FVC % predicted (FVCpp) over Part A (Week 26)
2. Time to IPF progression through 26 weeks (the end of Part A), as defined by a decline from baseline in FVCpp of 5% or greater, or death
3. Time to hospitalization due to respiratory cause (as determined by the investigator) or all cause mortality through 26 weeks
4. Time to hospitalization due to respiratory cause (as determined by the investigator) through 26 weeks
5. Time to all-cause mortality through 26 weeks
6. Change from baseline to Week 26 in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) total score
7. Change from baseline to Week 26 in St. George’s Respiratory Questionnaire – IPF Version (SGRQ-I)
8. Change from baseline to Week 26 in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ-5D)
9. Change in serum biomarkers from baseline through Week 26
10. Number and duration of respiratory hospitalizations or pulmonary exacerbations (as determined by the investigator) through 26 weeks
11. Rate of hospitalization due to respiratory cause (as determined by the investigator) through 26 weeks
12. Part B: Rate of decline in FVCpp from the end of Part A (Week 26) to the end of Part B Period 1 (Week 52) Change in FVCpp from the end of Part A (Week 26) to the end of Part B Period 1 (Week 52)
13. Part B: Rate of decline in FVC (in mL) from the end of Part A (Week 26) to the end of Part B Period 1 (Week 52) using the values obtained from spirometry assessments
14. Part B: Time to IPF progression in Part B, as defined by a decline from the end of Part A (Week 26) to the end of Part B Period 1 (Week 52) in FVCpp of 5% or greater, or death
15. Part B: Time to hospitalization due to respiratory cause (as determined by the investigator) from the start of Part B (Week 26) through the end of Part B Period 1 (Week 52)
16. Part B: Time to all-cause mortality from the start of Part B (Week 26) through the end of Part B Period 1 (Week 52)
17. Part B: Time to hospitalization due to respiratory cause (as determined by the investigator) or all-cause mortality from the start of Part B (Week 26) through the end of Part B Period 1 (Week 52)
18. Part B: Total duration on assigned dose from the start of Part B through the end of Part B Period 1 (Week 52)
19. Part B: Change in EQ-5D from the end of Part A (Week 26) through the end of Part B Period 1 (Week 52)
20. Part B: Change in serum and plasma biomarkers from the end of Part A (Week 26) through the end of Part B Period 1 (Week 52)
21. Part B: Number and duration of respiratory hospitalizations or pulmonary exacerbations(as determined by the investigator) from the start of Part B (Week 26) through the end of Part B Period 1 (Week 52)
22. Part B: Rate of hospitalization due to respiratory cause (as determined by the investigator) from the start of Part B (Week 26) through the end of Part B Period 1 (Week 52)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Puretech Lyt 100 Inc.

Sponsor organisation

Puretech Lyt 100 Inc.

Address

6 Tide Street Suite 400

City

Boston

Postcode

02210-2412

Country

United States

Scientific contact point

Organisation

Puretech Lyt 100 Inc.

Contact name

Sarah Santipadri

Public contact point

Organisation

Puretech Lyt 100 Inc.

Contact name

Sarah Santipadri

Third parties 11

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications