An Investigational Study to Evaluate the Safety and Tolerability of Single and Multiple Ascending Doses of A-005

A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of A-005 in Healthy Adult Subjects

This is a 3-part study. Parts A and B are randomized, double-blind, placebo-controlled, multi-cohort investigations to assess the safety, PK, and PD of single ascending doses (SAD; Part A) and multiple ascending doses (MAD; Part B) of orally-administered A-005. Part C is optional and will be an open-label, one-cohort, single dose study to assess the penetration of orally-administered A-005 into the CSF (Cerebrospinal fluid).

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4) (A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.)

Inclusion Criteria:

• Healthy, adult, male or female 19-55 years of age, inclusive, at the screening visit.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit.
• Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, and vital signs
• No ECG findings of clinical significance
• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

• History or evidence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
• Creatinine phosphokinase levels > ULN at the screening visit.
• Clinically significant laboratory abnormalities in white blood cell count, absolute neutrophil count, or absolute lymphocyte count at the screening visit.
• Triglyceride levels > ULN at the screening visit.
• Clinically significant abnormalities on urinalysis at the screening visit.
• Any history of malignant disease excluding surgically resected skin squamous cell or basal cell carcinoma.
• Presence of clinically relevant immunosuppression from immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Presence or evidence of recent sunburn, scar tissue, tattoo (more than 25% of body area), open sore, or branding that, in the opinion of the PI or designee, would interfere with interpretation of skin adverse reaction assessments, and, for Part C only, with the lumbar puncture.
• Positive test results for active human immunodeficiency virus (HIV-1 and HIV-2), hepatitis B surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb), or hepatitis C virus (HCV) antibodies at the screening visit.
• Any positive responses within the past 12 months and in the opinion of the PI or designee on the C-SSRS at the screening visit or at first check-in (Day -1).
• Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Exception: cholecystectomy is allowed.
• Use of any vaccinations, other than the COVID-19 vaccination, within 30 days prior to the first dosing. For the COVID-19 vaccination, the first or second vaccination must be received at least 15 days prior to the dosing.
• Participation in another investigational clinical trial within 30 days (or 5 half-lives of the investigational agent) (whichever is longer) for small molecules and within 60 days for biologic compounds (or for the anticipated duration of the biologic compound's PD effects, whichever is longer), prior to the first dosing.
• Any other condition or prior therapy that in the opinion of the PI or designee would make the subject unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
• For Part C only: Subjects with bleeding disorders, relevant lab abnormalities (Screening international normalized ratio greater than 1.4, platelets less than 50), prior intolerance of lumbar puncture, anatomical reasons preventing safe or successful collection of fluid (skin infection at site of puncture, relevant spine surgery, spinal deformity, etc.), known intracranial space-occupying lesions with mass effect, posterior fossa masses, or relevant brain malformations (Arnold-Chiari malformation, etc.), exam findings suggestive of increased intracranial pressure, or known allergy/sensitivity to lidocaine or its derivatives will not be eligible.