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

NCT05965414 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: ATI-CS-0011R44AG076299
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (14)

• Safety and tolerability of CS6253

  All treatment emerging Adverse Events (TAEs) will be recorded until the SAD: Day 4 and MAD: Day 13

  SAD: After dosing and until 72 hours after dosing; MAD: After dosing until day 13 (72 hours after the last dosing on day 10)

• SAD-Plasma: AUC0-last

  Area under the concentration-time curve until the last quantifiable concentration

  Pharmacokinetics (PK) samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: AUC0-inf

  Area under the concentration time curve from time 0 extrapolated to infinity

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: Cmax

  Maximum observed plasma concentration (eg C0)

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: Kel

  Terminal elimination rate constant

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: t1/2

  Terminal elimination half-life

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: Clearance (CL/F)

  Apparent clearance

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Plasma: Vd/F

  Apparent volume of distribution

  PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:

• SAD-Cerebrospinal Fluid (CSF): AUC0-last

  In cohorts 3-5:Area under the concentration-time curve in CSF until the last quantifiable concentration

  PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.

• SAD-CSF: Cmax

  In cohorts 3-5:Maximum observed CSF concentration (eg C0)concentration

  PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.

• MAD-Plasma: AUC0-last

  Area under the concentration-time curve until the last quantifiable concentration

  PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.

• MAD-Plasma: Cmax

  Maximum observed plasma concentration (eg C0)

  PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.

• MAD-CSF:AUC0-last

  Area under the concentration-time curve until the last quantifiable concentration

  CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.

• MAD-CSF: Cmax

  Maximum observed CSF concentration (eg C0)

  CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.

Study Arms (2)

CS6253 Solution for Injection

ACTIVE COMPARATOR

SAD: Single ascending doses: CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution MAD: Multiple ascending doses (4x every 72 hours): CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution

Drug: CS6253 Solution for Injection

Placebo

PLACEBO COMPARATOR

SAD and MAD: Placebo control will be provided from vials containing physiological saline for injection in an equal amount as necessary for the active arm.

Drug: Placebo

Interventions

CS6253 Solution for Injection DRUG

Solution for intra-venous injection, 50mg CS6253 /mL. Single-use vials containing 100 mg CS6253 (2 mL of 50 mg/mL concentration)

CS6253 Solution for Injection

Placebo DRUG

Physiological saline solution for intra-venous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male HVs at least 18 years old.
• a) Cohort 5 only: Male and female HVs at least 50 years old and if female be of non-childbearing potential, i.e. meet at least one of the following criteria: postsurgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or postmenopausal (amenorrheic for at least 2 years and a serum follicle-stimulating hormone (FSH) \> 30 IU/L).
• b) If subject is male, must be willing to use acceptable contraception from Day 1 until 30 days after the last dose of study drug.
• The subject has a body mass index (BMI) within 18-32 kg/m² (inclusive).
• The subject is in reasonably good health as determined by medical history and physical examination and clinical laboratory tests.
• The subject is willing and able to speak, read, and understand Spanish and give signed informed consent.
• The subject must agree to comply with a lumbar catheterization and collection of blood and CSF samples (SAD Cohorts 3-5 only and MAD cohorts).
• The subject is willing and able to comply with all testing and requirements defined in the protocol.
• The subject is willing, deemed compliant, and able to remain at the Clinical Research Unit (CRU) for the duration of the confinement period and return for all outpatient visits.
• Phase 1B MAD
• The eligibility criteria for the Phase 1B MAD study are the same as described for Phase 1A SAD, with the following exceptions:
• At least 50 years old and female need to be of non-childbearing potential
• Known to have at least 1 APOE4 allele (homozygous or heterozygous). Note: this criterion applies to on average for the MAD at least 4 APOE4 subjects per cohort.

You may not qualify if:

• Subjects who meet any of the following criteria will not be enrolled:
• The subject has any clinically significant deviations from normal in physical examination, ECG, or clinical laboratory tests, as determined by the investigator.
• The subject has an increased bleeding risk or is treated with anti-coagulation therapies including but not limited to aspirin, coumarin, warfarin and heparin.
• The subject has had a clinically significant illness within 30 days of check-in, as determined by the investigator.
• The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease.
• History of Type 2 diabetes mellitus or hemoglobin A1c (HbA1c) \> 7%.
• Fasting triglycerides \> 400 mg/dL
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 (Cockcroft-Gault formula)
• The subject has changed the frequency or dose of chronic medication within the last 8 weeks.
• The subject has a history of substance abuse or a positive alcohol or urine drug screen at screening or at check-in.
• The subject has a positive serum hepatitis B surface antigen or positive anti-hepatitis C virus test at the Screening Visit.
• Have positive test results for, or evidence of active infection with, human immunodeficiency virus type 1 or 2, or hepatitis B, or C.
• The subject has received an investigational drug within 30 days of Check-in.

Sponsors & Collaborators

• Artery Therapeutics, Inc.: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

La Paz University Hospital

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Injections

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Alberto M. Borobia Perez, MD, Ass.Prof

  Universidad Autónoma de Madrid, Farmacología y Terapéutica / Facultad de Medicina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Neither the investigator nor the subject will know who has received the study drug or the placebo, The injections will be prepared by an unblinded pharmacist according to the randomization list.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SAD: 5 cohorts 8 of healthy volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo). MAD: 2 or more cohorts 8 of healthy male and female volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo). The subjects will be stratified on their APOE4 status. Each cohort needs to have at least 4 APOE4 carriers.

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: July 28, 2023
• Study Start: October 23, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)