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

Phase 1

Conditions: Idiopathic Pulmonary Fibrosis (IPF)
MedDRA version: 21.1Level: PTClassification code 10021240Term: Idiopathic pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2021-006820-41-GR

Lead Sponsor: PureTech LYT 100, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1. Written or electronic informed consent from the participant prior to
any study procedures in a manner approved by an IRB, IEC, or 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 ATS/ ERS/JRS/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 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 90 days from cessation of study
medication
Part B:
1. Signed informed consent for Part B prior to any study-mandated
procedures
2. Participant must have completed Part A of the study, through Day 183
of treatment
3. In the opinion of the investigator, the participant is a good candidate
for continued treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1.Participants who, in the judgement of the investigator, are unlikely to
be able to fulfill study participation requirements
2.Significant clinical worsening (as per investigator's discretion) of IPF
between Screening and Baseline Visits
3.AST or ALT>1.5 × ULN at Visit 1
4.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
5.Creatinine clearance <30 mL/min calculated by Cockcroft–Gault
formula at Visit 1
6.Participants with underlying chronic liver disease (Child-Pugh B or C
hepatic impairment)
7.Current or prior treatment with pirfenidone
8.Other investigational therapy received within 1 month prior to
randomization visit (Visit 2)
9.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 inhaled requiring 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
10.Primary obstructive airway physiology (pre-bronchodilator FEV1/FVC
<0.7 at Visit 1)
11.Known explanation for interstitial lung disease, including but not
limited to radiation, sarcoidosis, hypersensitivity pneumonitis,
bronchiolitis obliterans organizing pneumonia, HIV, viral hepatitis, and
cancer
12.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
13.In the opinion of the investigator, other clinically significant
pulmonary abnormalities, including prior or current lung cancer (treated
within the past 5 years)
14.Major extrapulmonary physiological restriction (eg, chest wall abnormality, large pleural effusion)
15.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
16.Prior hospitalization within 3 months prior to Visit 1 for
confirmed COVID-19, acute exacerbation of IPF, or any lower
respiratory tract infection
17.Known symptoms of dysphagia or known difficulty in swallowing
capsules or tablets and/or total gastrectomy
18.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 teriflunomide (inducers of CYP1A2)
b.Medications associated with substantial risk for prolongation of the
QTc interval (including but not limited to moxifloxacin, quinidine,
procainamide, amiodarone, sotalol)
c.Immunosuppressant medications such as azathioprine,
cyclophosphamide, cyclosporin A, methotrexate, prednisone at a steady
dose >10mg/day or equivalent
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 dysfunction are
allowed), guanylate cyclase stimulators (eg, riociguat), prostacyclin
analogs (eg, epoprostenol, treprostnil, iloprost), or prostacyclin receptor
agonists (

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To obtain clinical data establishing the efficacy, tolerability, safety, and dosing regimen of LYT-100 in patients with IPF.;Secondary Objective: Part B Objectives:<br>• Assess the safety and tolerability of long-term treatment with LYT-100<br>in the IPF population<br>• Compare the rate of change in FVC through the end of Part B Period 1<br>to that observed during Part A, by Part A treatment group assignment<br>and by Part B LYT-100 target dose;Primary end point(s): Rate of decline in FVC (in mL) over Part A (26 weeks);Timepoint(s) of evaluation of this end point: at week 26

Secondary Outcome Measures

Name	Time	Method

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