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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: A-005; Drug: A-005; Drug: Placebo

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.)

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Single Ascending Dose (SAD)	Drug: A-005; Single oral dose of A-005; Drug: A-005; Multiple doses of A-005; Drug: Placebo; A-005 matched placebo
Experimental: Part B: Multiple Ascending Dose (MAD)	Drug: A-005; Single oral dose of A-005; Drug: A-005; Multiple doses of A-005; Drug: Placebo; A-005 matched placebo
Experimental: Part C: Lumbar Puncture	Drug: A-005; Single oral dose of A-005; Drug: A-005; Multiple doses of A-005

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples.	4 days
Assess the PK parameters of A-005 via time of maximum plasma concentration (Tmax)	Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples.	4 days
Assess the PK parameters of A-005 via the maximum plasma concentration (Cmax)	Relative bioavailability and food effect assessment via collection and comparison of PK plasma samples.	4 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess A-005 penetration in the CSF	Measurement of A-005 in the CSF	4 days

Collaborators and Investigators

• Sponsor: Alumis Inc
• Investigators: Study Director: Jorn Drappa, Medical Director, Alumis Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: A-005-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The Sponsor Alumis Inc. is a clinical-stage pharmaceutical company that has not yet adopted an Individual Participant Data (IPD) sharing plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No