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

Sponsor

Lung Therapeutics, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT04233814

Collaborator

(none)

Enrollment

Location

Arms

23.1

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

71 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

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.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.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

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.

Primary Purpose:

Other

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Ph 1a, First-in-Man, Single Ascending Dose & Multiple Ascending Dose Safety, Tolerability and PK Study of a Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) in Healthy Adult Subjects

Actual Study Start Date :

Jan 20, 2020

Actual Primary Completion Date :

Dec 23, 2021

Actual Study Completion Date :

Dec 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Placebo Matching placebo is a micronized lactose powder administered by inhalation through a dry powder inhaler (DPI)	Drug: Placebo Matching placebo is micronized lactose powder administered by inhalation through a dry powder inhaler.
Experimental: SAD Cohort 1 LTI-03 20 mg delivered qd x 1 day via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: SAD Cohort 2 LTI-03 40 mg delivered qd x 1 day via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: SAD Cohort 3 LTI-03 80 mg delivered qd x 1 day via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: MAD Cohort 1 LTI-03 dose at 20mg once daily x 14 days via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: MAD Cohort 2 LTI-03 dose at 40mg once daily x 14 days via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: MAD Cohort 3 LTI-03 dose at 2.5 mg once daily x 14 days via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: MAD Cohort 4 LTI-03 dose at 5 mg once daily x 14 days via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.
Experimental: MAD Cohort 5 LTI-03 dose at 5 mg twice daily x 14 days via DPI	Drug: Caveolin-1-Scaffolding-Protein-Derived Peptide (LTI-03) 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.

Outcome Measures

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events (TEAE) [up to 49 days]
Incidence of TEAE by system-organ class and dose group as assessed by the Toxicity Grading Scale for Healthy Adult Volunteers

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

History of asthma
Presence 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 or designee
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
Pulmonary function outside the normal range, including forced expiratory volume 1 (FEV1), forced vital capacity (FVC) each < 80% of predicted or FEV1/FVC ratio of ≤ 0.7 at Screening
Inability to use study inhaler device appropriately.
Positive test results for human immunodeficiency virus (HIV) HIV-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAG) or hepatitis C virus antibody (HCV-AB) Concurrent Intake of Other Substances
History of alcohol abuse within one year prior to Screening or regular use of alcohol of ≥ 14 units of alcohol per week for females and ≥ 21 units of alcohol for males (1 unit = 150 mL wine, 360 mL beer or 45 mL of 40% alcohol) within 6 months prior to dosing or a positive urine alcohol test at Screening or Day -1
History of drug abuse or misuse within 5 years prior to dosing or a positive urine drug test at Screening or Day -1
Inability or unwillingness to abstain from alcohol or any drug of abuse for 48 hours prior to the first dose until completion of the Day 8 visit for the SAD and Day 21 visit for the MAD
Exposure to any live vaccines within 28 days prior to dosing
Treatment with an investigational product within 30 days or 5 half-lives (whichever is longer) prior to dosing
Use of prescription or non-prescription medications and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements must be discontinued 28 days prior to dosing. Approved medications taken for contraception are permitted.
Positive serum pregnancy test in female subjects
Female subjects who are lactating
Female subjects 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 medication. Male subjects who do not agree to refrain from donating sperm during this same period.
Not eligible to receive study medication within 2 weeks of receiving a COVID-19 vaccination, including an initial, second, or booster injection.

NOTE: Female who is surgically sterile or post-menopausal for at least 12 months with follicle stimulating hormone (FSH) > 30 mIU/ml, are not considered to be of childbearing potential.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Belfast		United Kingdom	BT9 6AD

Sponsors and Collaborators

Lung Therapeutics, Inc

Investigators

Principal Investigator: Devinda Weeraratne, MD, Celerion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Lung Therapeutics, Inc

ClinicalTrials.gov Identifier:

NCT04233814

Other Study ID Numbers:

LTI-03-1001

First Posted:

Jan 18, 2020

Last Update Posted:

Mar 7, 2022

Last Verified:

Mar 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis

Study Results

No Results Posted as of Mar 7, 2022