Healthy Volunteer
Conditions
Brief summary
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).
Detailed description
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.)
Interventions
DRUGA-005
Single oral dose of A-005
DRUGPlacebo
A-005 matched placebo
Sponsors
Alumis Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of nonserious adverse events (AE), serious adverse events (SAE), and AE in single oral dose administration of A-005 in healthy adult subjects. | 4 days |
| Incidence of nonserious adverse events (AE), serious adverse events (SAE), and AE in multiple oral dose administration of A-005 in healthy adult subjects | 17 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following single oral dose administration of A-005 in healthy subjects via area under the concentration time curve (AUC) | 4 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following single oral dose administration of A-005 in healthy subjects via time of maximum plasma concentration (Tmax) | 4 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following single oral dose administration of A-005 in healthy subjects via maximum plasma concentration (Cmax) | 4 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following single oral dose administration of A-005 in healthy subjects via terminal elimination half-life (t1/2) | 4 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following multiple oral dose administration of A-005 in healthy subjects via area under the concentration time curve (AUC) | 17 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following multiple oral dose administration of A-005 in healthy subjects via time of maximum plasma concentration (Tmax) | 17 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following multiple oral dose administration of A-005 in healthy subjects via maximum plasma concentration (Cmax) | 17 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in plasma following multiple oral dose administration of A-005 in healthy subjects via terminal elimination half-life (t1/2) | 14 days | — |
| To assess the pharmacokinetics (PK) parameters of A-005 in urine following single oral dose administration of A-005 in healthy subjects via cumulative amounts of unchanged A-005 | 4 days | — |
| Change from baseline in ECG parameter ΔQTc interval in Part A: SAD | 24 hours | — |
| Change from baseline in ECG parameter ΔQTc interval in Part B: MAD | 48 hours | — |
| Assess the PK parameters of A-005 via area under the concentration time curve (AUC) | 4 days | Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples. |
| Assess the PK parameters of A-005 via time of maximum plasma concentration (Tmax) | 4 days | Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples. |
| Assess the PK parameters of A-005 via the maximum plasma concentration (Cmax) | 4 days | Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples. |
Countries
United States
Contacts
STUDY_DIRECTORJorn Drappa, Medical Director
Alumis Inc
Outcome results
None listed