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
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
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.
Inclusion Criteria:
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.