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Alzheimer DiseasePhase 1CMS121NCT05318040

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

A Phase 1 study testing CMS121 in people with Alzheimer Disease, run by Virogenics, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease
What is being tested?
CMS121
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
99 participants
Where
1 siteUnited States
Study dates
1 May 2022to 17 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • To qualify for enrollment, subjects must meet all of the following inclusion criteria:
  • 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.
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  • 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:
  • hysteroscopic sterilization;
  • bilateral tubal ligation or bilateral salpingectomy;
  • hysterectomy;
  • bilateral oophorectomy. or
  • Individuals who are postmenopausal (PMP) with amenorrhea for at least 1 year prior to the first dosing and follicle stimulating hormone (FSH) serum levels consistent with PMP status.
  • Females of childbearing potential and male subjects must follow protocol-specified contraception guidance.
  • Vital signs must be within the protocol-specified ranges.
  • No presence of a clinically significant ECG abnormality as judged by the PI or qualified designee and as per protocol-specified ranges.
  • Part 3 (Elderly):
  • Healthy, adult, male or female, 65-85 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:
  • hysteroscopic sterilization;
  • bilateral tubal ligation or bilateral salpingectomy;
  • hysterectomy;
  • bilateral oophorectomy. or
  • Individuals who are postmenopausal (PMP) with amenorrhea for at least 1 year prior to the first dosing and follicle stimulating hormone (FSH) serum levels consistent with PMP status.
  • or
  • Individuals who are PMP with amenorrhea for at least 1 year prior to the first dosing and FSH serum levels consistent with PMP status.
  • Females of childbearing potential and male subjects must follow protocol specified contraception guidance.
  • Vital signs must be within the protocol-specified ranges.
  • QTcF interval is ≤450 msec (males) or ≤470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit and prior to the first dosing.
  • Part 4 (Food Effect):
  • 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:
  • hysteroscopic sterilization;
  • bilateral tubal ligation or bilateral salpingectomy;
  • hysterectomy;
  • bilateral oophorectomy. or
  • Individuals who are PMP with amenorrhea for at least 1 year prior to the first dosing and FSH serum levels consistent with PMP status.
  • Females of childbearing potential and male subjects must follow protocol specified contraception guidance.
  • Vital signs must be within the protocol-specified ranges.
  • QTcF interval is ≤450 msec (males) or ≤470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit and prior to the first dosing.
  • Able to completely consume a standardized high-fat/high-calorie breakfast as required by the study protocol.

Who cannot join

  • 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.
Show all 60Show fewer
  • 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.
  • Heavy caffeine drinker (defined as consumption of >5 servings of caffeinated beverages [e.g., coffee, tea, cola, energy drinks] per day).
  • Refusal to refrain from strenuous physical activity from screening until first check-in.
  • Unwillingness to avoid sun and/or phototherapy exposure for 72 hours after the last dose of study drug.
  • Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing.
  • Use of any investigational drug or device within 30 days or biologics for 90 days (or 5 half-lives of the drug, whichever is the longer) prior to the first dosing, or currently participating in another study of an investigational drug or biologics, or a medical device.
  • Loss or donation of >500 mL blood within 56 days prior to study drug administration, or donation of plasma within 30 days prior to the first dosing.
  • Employee or family member of the PI, study site personnel, or Sponsor.
  • Any other reason that, in the opinion of the PI, would render the subject unsuitable for study enrollment.
  • Parts 1 (SAD):
  • History or presence of:
  • risk factors for Torsade de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome or sudden unexpected cardiac death at a young age);
  • sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities;
  • ischemic heart disease, symptomatic arrhythmias, or poorly controlled hypertension.
  • conditions predisposing to QT prolongation including pathological Q-wave.
  • Unable to refrain from or anticipates the use of:
  • any drugs, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing;
  • any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to the first dosing. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of PK/pharmacodynamic (PD) interaction with study drug;
  • any drugs that prolong the QT/QTc interval within 14 days (or 5 half-lives, whichever is longer) prior to the first dosing.
  • Allergy to band aids, adhesive dressing, or medical tape.
  • Glomerular filtration rate (GFR) ≤ 80 mL/min/1.73 m2, as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
  • Part 2 (MAD):
  • History or presence of:
  • risk factors for Torsade de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome or sudden unexpected cardiac death at a young age);
  • sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities;
  • ischemic heart disease, symptomatic arrhythmias, or poorly controlled hypertension.
  • conditions predisposing to QT prolongation including pathological Q-wave.
  • Unable to refrain from or anticipates the use of:
  • any drugs, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing;
  • any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to the first dosing. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of PK/PD interaction with study drug;
  • any drugs that prolong the QT/QTc interval within 14 days (or 5 half-lives, whichever is longer) prior to the first dosing.
  • Is at risk of suicide. Has attempted suicide in the past 12 months or Is at risk of suicide, as determined by the PI, psychiatric interview and/or the baseline C-SSRS.
  • Allergy to band aids, adhesive dressing, or medical tape.
  • GFR ≤ 80 mL/min/1.73 m2, as estimated by the CKD-EPI equation.
  • Part 3 (Elderly):
  • Is at risk of suicide. Has attempted suicide in the past 12 months or Is at risk of suicide, as determined by the PI, psychiatric interview and/or the baseline C-SSRS.
  • Unable to refrain from or anticipates the use of:
  • any drugs, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing. Thyroid hormone replacement medication (refer to protocol) will be allowed;
  • any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to the first dosing. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of PK/PD interaction with study drug.
  • GFR ≤ 70 mL/min/1.73 m2, as estimated by the CKD-EPI equation.
  • Part 4 (Food Effect):
  • Is lactose intolerant.
  • Unable to refrain from or anticipates the use of:
  • any drugs, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing;
  • any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to the first dosing. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of PK/PD interaction with study drug.
  • GFR ≤ 80 mL/min/1.73 m2, as estimated by the CKD-EPI equation.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Celerion

    Lincoln, Nebraska, 68502-2040

Other trials in United States

About this study

Official title: Phase 1 Study Evaluating Safety and Tolerability of Escalating Single and Multiple Doses of CMS121 and Food Effect in Healthy Volunteers

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.

Read the detailed description

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 approximately 36 days. Part 2 will be a MAD study enrolling approximately 32 young subjects for a total duration of approximately 43 days, and Part 3 will be a MAD study enrolling approximately 8 elderly subjects for a total duration of approximately 43 days. Part 4 will be an open-label SAD cross-over cohort of approximately 12 young subjects in fed and fasted states to evaluate the effect of food on the bioavailability of CMS121, for a duration of 36 days. Safety will be assessed by periodic measurement of vital signs, physical examinations, electrocardiograms (ECGs), blood and urine lab analyses and occurrence of adverse events (AEs).

Being tested
CMS121, Placebo
Keywords
Alzheimer's Disease
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CMS121Drug

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

  • PlaceboDrug

    Placebo will be provided as visually matching placebo capsules.

Study groups in NCT05318040
Study groupRoleWhat they receive
Single ascending dose - CMS121ExperimentalSubjects will receive a single oral dose of CMS121 under fed conditions.
Receives: Drug: CMS121
Single ascending dose - placeboPlacebo comparatorSubjects will receive a single oral dose of placebo under fed conditions.
Receives: Drug: Placebo
Multiple ascending dose - CMS121ExperimentalSubjects will receive multiple oral doses of CMS121 once daily (QD) for 7 days under fed conditions.
Receives: Drug: CMS121
Multiple ascending dose - placeboPlacebo comparatorSubjects will receive multiple oral doses of placebo once daily (QD) for 7 days under fed conditions.
Receives: Drug: Placebo
Multiple ascending dose - Elderly cohort - CMS121ExperimentalSubjects will receive multiple oral doses of CMS121 once daily (QD) for 7 days under fed conditions.
Receives: Drug: CMS121
Multiple ascending dose - Elderly cohort - placeboPlacebo comparatorSubjects will receive multiple oral doses of placebo once daily (QD) for 7 days under fed conditions.
Receives: Drug: Placebo
Food Effect - CMS121ExperimentalOn 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.
Receives: Drug: CMS121

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety: Treatment-emergent adverse events (TEAEs)

    Number of participants with TEAEs

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

Secondary outcomes (3)

  1. Pharmacokinetics (PK): Blood concentration levels of CMS121

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

  2. Pharmacokinetics (PK): Urine concentration levels of CMS121

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

  3. Safety: Effect on electrocardiographic parameters

    CMS121 concentration and effect on interval change in QTc (dQTc) from baseline

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2022
  2. Study start1 May 2022
  3. Primary completion17 Dec 2022
  4. Study completion17 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
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.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
99 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05318040
Sponsor's protocol ID
VG-CMS121-101
Other IDs
R01AG074447
Acronym
CMS121
Status last verified
Feb 2023
First submitted
31 Mar 2022
Last updated
16 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CMS121 in people with Alzheimer Disease, run by Virogenics, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 53 inclusion and 60 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety: Treatment-emergent adverse events (TEAEs) (time frame: From baseline through day 8 for SAD cohorts and through day 15 for MAD cohorts). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05318040.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023.

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