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A Phase 2 Study of LTI-03 in Patients With Idiopathic Pulmonary Fibrosis

R

Rein Therapeutics

Status and phase

Active, not recruiting
Phase 2

Conditions

Idiopathic Pulmonary Fibrosis (IPF)

Treatments

Device: Dry Powder Inhaler
Drug: Placebo
Drug: LTI-03

Study type

Interventional

Funder types

Industry

Identifiers

NCT06968845
LTI-03-2001 (RENEW)

Details and patient eligibility

About

Rationale: LTI-03 is an experimental medication breathed into the lungs using an inhaler. It is being studied for the treatment of Idiopathic Pulmonary Fibrosis (IPF). IPF is a progressive, fatal lung disease caused by the death of lung cells involved in oxygen uptake and by progressive fibrosis (scarring) of the lungs. As the disease progresses, patients experience loss of lung function and increased breathing problems. LTI-03 is hypothesized to treat IPF by protecting and restoring the function of the oxygen uptake cells and by controlling lung fibrosis which may result in improving lung scarring.

The purpose of this research is to evaluate LTI-03 including: its safety, whether it causes side effects, whether it improves lung scarring, and whether it improves IPF symptoms. LTI-03 will be compared to placebo in patients diagnosed with IPF within the last 5 years. Patients on a stable dose of nintedanib, pirfenidone, or nerandomilast (if available by prescription) may participate.

Trial Design: This is a Phase 2, randomized, double-blind, placebo-controlled, multi-center study that includes a 28-day Screening Period, a 24-week Treatment Period, and 4-week Follow-up Period.

Study Assessments: Up to 9 visits to the study clinic will be required.

Safety and tolerability will be evaluated with the following assessments: physical examination; collection of vital sign data (heart rate, blood pressure, respiratory rate and peripheral oxygen saturation [SpO2] via pulse oximetry); heart data collected by 12-lead electrocardiogram; and collection of blood samples for safety laboratory tests. In addition, participants will be asked about any adverse events (side effects) they have experienced between clinic visits, if they have changed any medications, and if they are able to properly use their study drug inhaler.

Participants will undergo a lung function test (spirometry) at every visit, which will be used to evaluate both safety and efficacy. Another test measuring the diffusion capacity of the lungs for carbon monoxide (DLCO) will be required at Screening only.

Blood samples will also be collected at each visit to measure disease biomarkers. At select visits patients will be asked to complete the Living with Pulmonary Fibrosis questionnaire to evaluate their IPF symptoms. Participants will also undergo a specialized lung scan (HRCT) at Baseline and at the End of Treatment to measure changes in lung fibrosis.

Interventions: LTI-03 and placebo are provided in powder-filled capsules that participants will self- administer using an inhaler. Placebo capsules look like LTI-03 capsules but have no active ingredients. Approximately 120 participants will be randomly assigned in a blinded manner to one of study drug treatment groups.

Enrollment

120 estimated patients

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Male or female age 40 years or older.
  2. Willing and able to provide written informed consent.
  3. Diagnosis of IPF within 5 years of Screening as confirmed by a centrally read HRCT of the chest as defined by the ATS/ERS/JRS/ALAT guideline. HRCT lung fibrosis by central read during screening must involve ≥ 10% of the lung and be greater than emphysema involvement of the lung.
  4. Forced vital capacity (FVC) percent predicted ≥ 45%.
  5. Diffusion capacity of the lungs for carbon monoxide (DLCO), hemoglobin-corrected percent predicted ≥ 30% within 8 weeks prior to Randomization.
  6. Participants receiving nintedanib, pirfenidone, or nerandomilast (where approved for marketing) for IPF treatment must have been on a stable prescribed dose for at least 12 weeks prior to Randomization.
  7. Participants who previously received nintedanib, pirfenidone, or nerandomilast must have discontinued treatment at least 8 weeks prior to Randomization.
  8. Able to adequately self-administer study drug using the protocol-specified inhaler device.

Exclusion criteria

  1. Forced expiratory volume in 1 second (FEV1)/FVC < 0.7.

  2. Use of N-acetyl cysteine or other supplements including but not limited to quercetin, omega-3 fatty acids, dehydroepiandrosterone, polyphenols, and phytochemicals within 7 days prior to Randomization and through Week 24.

  3. Use of systemic corticosteroids at doses > 10 mg/day of prednisone or equivalent within 28 days prior to Randomization.

  4. Active smoker.

  5. Pulmonary exacerbation within 3 months prior to Screening.

  6. Febrile pulmonary illness requiring antibiotic treatment within 28 days prior to Randomization.

  7. Participation in a clinical study or treatment with an investigational drug or device within 28 days of the Screening Visit (or 5 half-lives of the investigational agent, whichever is longer).

  8. History or evidence at Screening of significant renal impairment with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2.

  9. History or evidence at Screening of significant hepatic impairment with bilirubin > 3 mg/dL (> 51.3 μmol/L) and albumin < 2.8 g/dL (<28 g/L) and PT prolongation > 6 sec or INR > 2.3 while not on anticoagulant medication.

  10. Active or history of malignancies within 5 years prior to Randomization, with the exception of localized nonmetastatic basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or prostate cancer.

  11. Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol; or an expected survival of less than 24 weeks.

    Contraception and Pregnancy

  12. Positive pregnancy test in female participants of childbearing potential (defined below).

  13. Female participants who are lactating.

  14. Females of childbearing potential (FOCBP) and men with partners of childbearing potential who do not agree to use an acceptable form of contraception for the duration of study treatment and for at least 90 days after the last dose of study drug. Male participants who do not agree to refrain from donating sperm during this same period.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

120 participants in 4 patient groups, including a placebo group

(1) 2.5 mg LTI-03 capsule BID
Experimental group
Description:
Caveolin-1-Scaffolding-Protein-Derived Peptide
Treatment:
Drug: LTI-03
Device: Dry Powder Inhaler
(2) 2.5 mg LTI-03 capsules BID
Experimental group
Description:
Caveolin-1-Scaffolding-Protein-Derived Peptide
Treatment:
Drug: LTI-03
Device: Dry Powder Inhaler
(1) Placebo capsule BID
Placebo Comparator group
Description:
Lactose powder
Treatment:
Drug: Placebo
Device: Dry Powder Inhaler
(2) Placebo capsules BID
Placebo Comparator group
Description:
Lactose powder
Treatment:
Drug: Placebo
Device: Dry Powder Inhaler

Trial contacts and locations

2

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Central trial contact

Shawna H. Evans; Steven A. Shoemaker, MD

Data sourced from clinicaltrials.gov

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