Safety, Tolerability and Pharmacokinetic Study of LTI-03 in Healthy Adult Subjects

NCT04233814 | Completed Phase 1 FDA Drug

• 1 other identifier: LTI-03-1001
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The current study will investigate the initial safety, tolerability, and PK profile of inhaled LTI-03 in healthy volunteers. In order to minimize exposure, the study will first test single ascending doses (SAD) of LTI-03 followed by multiple ascending dose (MAD) cohorts. Findings from this study will direct the clinical development of LTI-03 for the treatment of IPF The study subject population will include normal healthy male and female volunteers between 18 and 55 years of age (inclusive). Consistent with other trials involving inhaled medication, subjects must have normal pulmonary function at Screening and will be excluded if they have a history of active or recurring allergies, asthma, chronic obstructive pulmonary disease (COPD), chronic sinus drainage, chronic or acute cough or other respiratory condition deemed exclusionary by the Investigator. History of liver dysfunction or elevated bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values at Screening will also be grounds for exclusion.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (TEAE)

  Incidence of TEAE by system-organ class and dose group as assessed by the Toxicity Grading Scale for Healthy Adult Volunteers

  up to 49 days

Study Arms (9)

Placebo

SHAM COMPARATOR

Matching placebo is a micronized lactose powder administered by inhalation through a dry powder inhaler (DPI)

Drug: Placebo

SAD Cohort 1

EXPERIMENTAL

LTI-03 20 mg delivered qd x 1 day via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

SAD Cohort 2

EXPERIMENTAL

LTI-03 40 mg delivered qd x 1 day via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

SAD Cohort 3

EXPERIMENTAL

LTI-03 80 mg delivered qd x 1 day via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

MAD Cohort 1

EXPERIMENTAL

LTI-03 dose at 20mg once daily x 14 days via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

MAD Cohort 2

EXPERIMENTAL

LTI-03 dose at 40mg once daily x 14 days via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

MAD Cohort 3

EXPERIMENTAL

LTI-03 dose at 2.5 mg once daily x 14 days via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

MAD Cohort 4

EXPERIMENTAL

LTI-03 dose at 5 mg once daily x 14 days via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

MAD Cohort 5

EXPERIMENTAL

LTI-03 dose at 5 mg twice daily x 14 days via DPI

Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03)

Interventions

Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) DRUG

LTI-03, a Caveolin-1 scaffold protein-derived 7-amino acid peptide to be administered as a dry powder by inhalation through a dry powder inhaler.

MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; MAD Cohort 4; MAD Cohort 5; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3

Placebo DRUG

Matching placebo is micronized lactose powder administered by inhalation through a dry powder inhaler.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoker (no use of tobacco products within 6 months prior to dosing) with a negative urine cotinine test at Screening or Day -1
• Age of 18-55 years (inclusive)
• Body mass index (BMI) of 18 - 30.5 kg/m2 (inclusive)
• Body weight \> 50 kg
• Willing and able to provide written informed consent

You may not qualify if:

• History of asthma
• Pulmonary infiltrate or pneumonia within 6 months prior to dosing or acute infection within 14 days prior to dosing
• History of significant allergy or anaphylaxis
• Any clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease (excluding hay fever), as determined by the Investigator or designee
• Any current clinically relevant abnormalities identified by a detailed medical history, complete physical examination including blood pressure and heart rate measurement, and clinical laboratory tests (hematology, coagulation, urinalysis, clinical chemistries) at Screening or Day -1, as determined by the Investigator or designee
• Any clinically significant illness and/or surgery within 28 days prior to dosing
• Febrile illness within 7 days prior to dosing
• Weight loss \> 5 kg within 28 days prior to dosing
• Clinically significant 12-lead electrocardiogram (ECG) abnormalities or vital sign abnormalities (systolic blood pressure \< 90 mmHg or \> 140 mmHg, diastolic blood pressure \< 50 mmHg or \> 90 mmHg, or heart rate \< 45 beats per minute \[bpm\] or \> 100 bpm) at Screening or Day -1, as determined by the Investigator or designee
• History of, or existing severe, acute, chronic, and/or psychiatric medical condition(s), laboratory abnormality, or other medical concerns that may increase the risk associated with study participation or IMP administration which, in the judgment of the Investigator, would make the subject inappropriate for entry into the study
• History of cancer with the exception of adequately treated basal cell or squamous cell carcinoma of the skin
• Hemoglobin \< lower limit of normal (LLN)
• Abnormal liver function- alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 times the upper limit of the normal range (ULN)
• \- total bilirubin \> 1.5 times ULN
• Abnormal renal function: estimated glomerular filtration rate (eGFR) (modification of diet and renal disease \[MDRD\]) \< 55 mL/min/1.73 m2

Sponsors & Collaborators

• Rein Therapeutics: lead

Study Sites (1)

Celerion

Belfast, BT9 6AD, United Kingdom

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Devinda Weeraratne, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The Sponsor, Investigator, and study personnel working on behalf of the Investigator and Sponsor will remain blinded. Study medication will be dispensed by unblinded pharmacy staff to study staff in a blinded manner. Other than the pharmacist(s), all study staff will remain blinded to study medication assignment.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The first part of the study will follow a Single Ascending Dose design. Subjects receive a single dose of double-blind study medication (investigational medicinal product LTI-03 or placebo) on Day 1. For each dose level cohort, two eligible sentinel subjects will be randomized in a 1:1 ratio to receive active:placebo study medication. If no tolerability issues are observed by the Investigator within 48 hours post-dose, dosing will commence for the remaining six subjects in the cohort, who will be randomized in a 5:1 ratio to receive active:placebo study medication. The second part of the study will follow a Multiple Ascending Dose design. Subjects receive double-blind study medication (LTI-03 or placebo) once-daily from Day 1 to Day 14. For each dose level cohort, eight eligible subjects will be randomized in a 6:2 ratio to receive active:placebo study medication.

Study Record Dates

• First Submitted: January 12, 2020
• First Posted: January 18, 2020
• Study Start: January 20, 2020
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: March 7, 2022

Record last verified: 2022-03

Locations

GB (1)