NCT05965414

Safety and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of CS6253 in Healthy Volunteers

A Phase 1 Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of CS6253 in Healthy Volunteers and in APOE4 Carriers

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 66 (actual)
• Sponsor: Artery Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

Summary

* Phase 1A SAD: Five or more cohorts of 8 healthy volunteers (HVs) will receive a single IV bolus injection of study drug or placebo. The first 4 cohorts will be male only. The last cohort will be repeated with the max safe dose of the previous cohorts in healthy elderly subjects (male and female of non childbearing potential, \> 50years) * Phase 1B MAD: Two or more cohorts of 8 male and female HVs will receive multiple (4) IV bolus injections of study drug or placebo every 72 hours. * Phase 1 Subcutaneous SC Cohort: One cohort of 6 male and 6 female HVs will receive one SC injection of study drug.

Detailed description

This is a randomized, double-blind, placebo-controlled study in HV and in APOE4 carriers. Phase 1A Single Ascending Dose (SAD): In 5 or more sequential SAD cohorts of 8 (6 active:2 placebo) HVs a single IV bolus injection (CS6253 1, 2.4, 6, and 10 mg/kg or placebo) will be administered and PK, safety, and biomarkers will be assessed. The first 4 cohorts will include males only. In the fifth cohort 8 (6 active:2 placebo) subjects, male and female of non-childbearing potential and at least 50 years old, will be administered CS6253 at equal to or lower doses than the maximum safe SAD dose in HV. CSF will not be collected in the first 2 SAD cohorts. In the following cohorts, CSF will be collected before dosing and over 24 hours after dosing. Additional cohorts may be added as needed and deemed safe and appropriate by the Data Safety Monitoring Board (DSMB). Phase 1B Multiple Ascending Dose (MAD): In 2 or more sequential MAD cohorts of 8 (6 active:2 placebo) male and female HVs at least 50 years old on average ≥ 3/sex/cohort; ≥ 4 APOE4 carriers/cohort, will be administered multiple IV bolus injections. Cohort 1 will be administered CS6253 at 75% of the maximum safe SAD dose in subjects at least 50 years old or placebo, and if no Treatment Emerging Adverse Events (TEAEs), in Cohort 2 at 100% of the maximum safe SAD dose or placebo will be administered every 72 hours x 4 doses and PK, safety, and biomarkers will be assessed. Plasma PK will be assessed after first and fourth dose in all cohorts. CSF will be collected before dosing and over 24 hours in conjunction with the fourth dose. Cohorts of 8 subjects (6 active:2 placebo) may be added at doses equal to or lower than the maximum safe MAD dose to further explore CS6253 brain exposure and Pharmacodynamics (PD) dependency on APOE4 isoform and sex. Phase 1 Subcutaneous SC Cohort: One cohort of 6 (\>=4) male and 6 (\>=4) female HVs will receive one SC injection of study drug. From these 12 subjects (\>=4) female and (\>=4) male subjects need to be an APOE4 carrier.

Conditions

• Alzheimer's Disease

Interventions

Type	Name	Description
DRUG	CS6253 Solution for Injection	Solution for intra-venous injection, 50mg CS6253 /mL. Single-use vials containing 100 mg CS6253 (2 mL of 50 mg/mL concentration)
DRUG	Placebo	Physiological saline solution for intra-venous injection

Timeline

• Start date: 2023-10-23
• Primary completion: 2024-07-31
• Completion: 2024-07-31
• First posted: 2023-07-28
• Last updated: 2025-05-11

Locations

1 site across 1 country: Spain

Regulatory

• FDA-regulated drug study