Safety, Tolerability and Pharmacokinetics of CMS121, a Drug Candidate for Alzheimer's Disease, in Healthy Subjects

NCT05318040 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: VG-CMS121-101R01AG074447
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind study of CMS121 or placebo given as single and multiple escalating doses in normal healthy subjects. The study will be conducted in 4 parts: Part 1 will be a SAD study enrolling approximately 48 young subjects for a total duration of 36 days. Part 2 will be a MAD study enrolling approximately 32 young subjects for a total duration of 43 days, and Part 3 will be a MAD study enrolling approximately 8 elderly subjects for 43 days. Part 4 will be an open-label SAD cross-over cohort of approximately 12 young subjects in a fed or fasted state to evaluate the effect of food on the bioavailability of CMS121, for a duration of 36 days.

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Safety: Treatment-emergent adverse events (TEAEs)

  Number of participants with TEAEs

  From baseline through day 8 for SAD cohorts and through day 15 for MAD cohorts

Secondary Outcomes (3)

• Pharmacokinetics (PK): Blood concentration levels of CMS121

  From baseline on day 1 through day 4 for SAD cohorts and through day 10 for MAD cohorts

• Pharmacokinetics (PK): Urine concentration levels of CMS121

  From baseline on day 1 through day 4 for SAD cohorts and through day 10 for MAD cohorts.

• Safety: Effect on electrocardiographic parameters

  From baseline on day 1 and for 24hr post day 1 dose for SAD cohorts; from baseline on day 1 and for 24hr post-dose after day 7 dose for MAD cohorts.

Study Arms (7)

Single ascending dose - CMS121

EXPERIMENTAL

Subjects will receive a single oral dose of CMS121 under fed conditions.

Drug: CMS121

Single ascending dose - placebo

PLACEBO COMPARATOR

Subjects will receive a single oral dose of placebo under fed conditions.

Drug: Placebo

Multiple ascending dose - CMS121

EXPERIMENTAL

Subjects will receive multiple oral doses of CMS121 once daily (QD) for 7 days under fed conditions.

Drug: CMS121

Multiple ascending dose - placebo

PLACEBO COMPARATOR

Subjects will receive multiple oral doses of placebo once daily (QD) for 7 days under fed conditions.

Drug: Placebo

Multiple ascending dose - Elderly cohort - CMS121

EXPERIMENTAL

Subjects will receive multiple oral doses of CMS121 once daily (QD) for 7 days under fed conditions.

Drug: CMS121

Multiple ascending dose - Elderly cohort - placebo

PLACEBO COMPARATOR

Subjects will receive multiple oral doses of placebo once daily (QD) for 7 days under fed conditions.

Drug: Placebo

Food Effect - CMS121

EXPERIMENTAL

On Day 1 of each of 2 treatment periods, a single oral dose of CMS121 will be administered following either a standard high fat/high calorie meal (Treatment A) or an overnight fast (Treatment B), as per each subject's assigned randomization sequence (AB or BA). There will be a washout of at least 7 days between doses.

Drug: CMS121

Interventions

CMS121 DRUG

CMS121 is a small molecule to be delivered orally in capsule form and is a therapeutic drug candidate for treatment of Alzheimer's Disease

Food Effect - CMS121; Multiple ascending dose - CMS121; Multiple ascending dose - Elderly cohort - CMS121; Single ascending dose - CMS121

Placebo DRUG

Placebo will be provided as visually matching placebo capsules.

Multiple ascending dose - Elderly cohort - placebo; Multiple ascending dose - placebo; Single ascending dose - placebo

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects:
• Capable of understanding the written informed consent document; willingly provides valid, signed written informed consent; willing and able to comply with the study schedule, requirements, and restrictions.
• Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dosing.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit.
• In good general health, free from clinically significant medical or psychiatric illness, based on medical/surgical history, physical examination, and clinical laboratory tests.
• All laboratory parameters (serum chemistry, hematology, coagulation, and urinalysis) are within the reference range or considered not clinically significant by the PI, at the screening visit.
• Negative results for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) tests (as outlined in protocol) at the screening visit.
• Female subjects must have negative results for pregnancy test at the screening visit and the first check-in and must not be lactating.
• Able to swallow multiple capsules.
• Adequate venous access in the left or right arm to allow collection of the required blood samples.
• Parts 1 (SAD) and 2 (MAD):
• Healthy, adult, male or female, 19-60 years of age, inclusive, at the screening visit.
• Females of childbearing potential .
• Females of non-childbearing potential are defined as follows:
• Individuals who have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:

You may not qualify if:

• Subjects who meet any of the following criteria must be excluded from the study:
• All Subjects:
• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of malignancy within the past 2 years, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study in the opinion of the PI or designee.
• Evidence of clinically relevant medical illness including cardiovascular, hematological, psychiatric, gastrointestinal, hepatic, renal, rheumatologic, autoimmune, endocrine, pulmonary, neurologic or dermatologic disorder in the opinion of the PI or designee.
• History of skin rash(es) associated with the use of any medication(s).
• Any condition (e.g., chronic diarrhea) or prior surgery (e.g., gastric bypass) that could interfere with drug absorption, distribution, metabolism, or excretion.
• Clinically significant surgical procedure within 90 days prior to the screening visit.
• Clinically significant acute illness or infection within 14 days prior to the first dosing.
• History of significant drug allergies including a history of anaphylactic reaction.
• Family history of sudden death in an otherwise healthy individual.
• Positive urine cotinine at the screening visit or at first check-in.
• Excessive use of alcohol, defined as weekly intake in excess of 14 units of alcohol (1 unit = 12 fluid ounces of beer, 5 fluid ounces of wine, or 1.5 fluid ounces \[1 shot\] of distilled spirits or liquor), within 6 months prior to the screening visit.
• Positive test result for alcohol or drugs of abuse at the screening visit or first check-in, or history of alcohol and/or drug abuse within the past 2 years prior to the screening visit.

Sponsors & Collaborators

• Virogenics, Inc.: lead
• National Institute on Aging (NIA): collaborator
• Celerion: collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502-2040, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Scott Rasmussen, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double Blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 4-Part study. Parts 1, 2, and 3 are randomized, double blind, placebo-controlled investigations of SAD (Part 1) and MAD (Part 2) in healthy young adult subjects and multiple doses in healthy elderly subjects (Part 3) of orally administered CMS121. Part 4 is an open label, 2 way crossover study to assess the effect of food on a single oral dose of CMS121 in healthy young adult subjects.

Study Record Dates

• First Submitted: March 31, 2022
• First Posted: April 8, 2022
• Study Start: May 1, 2022
• Primary Completion: December 17, 2022
• Study Completion: December 17, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)