Phase 1 Study to Evaluate the Safety and Tolerability of 8M2D in Healthy People and Alzheimer's Patients

NCT07568041 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CN101
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is testing a new investigational drug called 8M2D to learn whether it is safe and well-tolerated in humans. 8M2D has not previously been given to people. Hypothesis: Researchers believe that 8M2D can be administered safely to healthy adults and to people with early Alzheimer's disease, and that it may reduce levels of amyloid beta. Amyloid beta is a protein that builds up in the brains of people with Alzheimer's disease and is thought to contribute to its progression. The study will be conducted in three parts. In the first two parts, healthy volunteers will receive either a single dose or multiple doses of 8M2D so researchers can understand how the drug moves through the body and whether it causes any side effects. In the third part, a small group of people with early Alzheimer's disease will receive multiple doses so researchers can also begin to assess whether the drug has any effect on amyloid beta levels. Doses will be increased gradually and carefully. An independent safety board will review safety information before any dose increase is allowed. The information gathered in this study will be used to identify the appropriate dose of 8M2D and to help design future studies in people with Alzheimer's disease.

Conditions

Alzheimer's Disease (AD)

Keywords

Alzheimer's disease; amyloid beta; Alzheimer's disease treatment; Alzheimer's disease prevention; Phase 1a/b clinical trial; Single Ascending Dose; Multiple Ascending Dose; first-in-human; safety, tolerability, and pharmacokinetics; exploratory immunogenicity

Outcome Measures

Primary Outcomes (14)

• Number of participants reporting treatment-emergent adverse events

  A treatment-emergent adverse event is defined as any adverse event that has an onset on or after the first dose of the trial medication, or any pre-existing condition that has worsened on or after the first dose of the trial intervention.

  Baseline to Day 44

• Number of participants reporting treatment-emergent adverse events that require discontinuation of therapy due to intolerable side effects

  Evaluation of the number of participants withdrawn from study medication due to treatment-emergent adverse events.

  Baseline to Day 14

• Number of participants reporting injection site reactions

  Evaluation of skin reactions at the injection site, including pain, itching, and swelling or redness around the injection site.

  Baseline to Day 22

• Number of participants demonstrating abnormal laboratory findings

  Evaluation of laboratory results outside the documented normal range as defined by the clinical laboratory.

  Baseline to Day 14

• Number of participants demonstrating abnormal vital signs

  Evaluation of absolute vital sign value and the changes from baseline that are outside the normal range.

  Baseline to Day 22

• Number of participants demonstrating abnormal vital electrocardiogram (ECG) parameters

  Evaluation of 12-lead ECG parameters.

  Baseline to Day 15

• Number of participants demonstrating adverse changes in physical and/or neurologic examinations

  Evaluation of the physical and/or neurological examinations conducted by site clinicians during the study period.

  Baseline to Day 22

• Number of participants reporting changes in Columbia-Suicide Severity Rating Scale (C-SSRS) from baseline

  The C-SSRS is a suicidal ideation and behavior rating scale to evaluate suicide risk. The total score ranges from 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent).

  Baseline to Day 22

• Maximum observed concentration (Cmax) of 8M2D

  Maximum concentration of 8M2D, determined directly from individual concentration-time data determined through plasma and CSF analysis.

  Baseline to Day 14

• Time to maximum observed concentration (tmax) of 8M2D

  Time of the maximum concentration of 8M2D determined through plasma and CSF analysis.

  Baseline to Day 14

• Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC-last) of 8M2D

  Evaluated from time-zero to the time of the last quantifiable concentration of 8M2D determined through plasma and CSF analysis.

  Baseline to Day 14

• Terminal phase half-life (t1/2)

  The observed terminal half-life of 8M2D determined through plasma and CSF analysis.

  Baseline to Day 14

• Area under the concentration-time curve from time 0 to infinity (AUC-inf)

  Area under the concentration-time curve from time-zero extrapolated to infinity.

  Baseline to Day 14

• Assessment of changes from baseline after 14 days of dosing in plasma and CSF biomarkers of AD [such as Aβ42, Aβ40, p-tau217, and np-tau217

  Evaluation of biomarkers of AD through plasma and CSF collected from all participants in Part III (AD) of the study.

  Baseline to Day 14

Secondary Outcomes (1)

• Assessment of the presence of anti-8M2D antibody in participants of all cohorts.

  Baseline to Day 22

Study Arms (4)

8M2D Single Ascending Dose (SAD) - healthy participants, Part I

EXPERIMENTAL

Part I (SAD) is a Phase Ia, First-in-Human, single-center, randomized, double-blind, placebo-controlled, dose escalating, SAD part of the clinical trial designed to evaluate the safety, tolerability, PK, and exploratory immunogenicity of single doses of 8M2D in healthy adult participants. Part I (SAD) will evaluate up to 5 dose levels of 8M2D. Approximately 30 eligible participants will be enrolled and assigned to 1 of 5 cohorts, with 6 participants per SAD cohort. In each of the SAD cohorts, 6 participants will be randomized in a 4:2 ratio (4 active: 2 placebo) to receive a single SC dose of 8M2D or matching placebo on Day 1. The intervention will be administered by subcutaneous injection.

Drug: 8M2D

8M2D Multiple Ascending Dose (MAD) - healthy participants, Part II

EXPERIMENTAL

Part II (MAD) is a Phase Ia, single-center, randomized, double-blind, placebo-controlled, dose escalating, MAD part of the clinical trial designed to evaluate the safety, tolerability, PK, and exploratory immunogenicity of multiple doses of 8M2D in healthy adult participants. Part II (MAD) will evaluate up to 3 dose levels of 8M2D. Approximately 18 eligible participants will be enrolled and assigned to 1 of 3 cohorts, with 6 participants per MAD cohort. In each of the MAD cohorts, 6 participants will be randomized in a 4:2 ratio (4 active: 2 placebo) to receive once-daily (QD) SC doses of 8M2D or matching placebo on Days 1 to 7. The intervention will be administered by subcutaneous injection.

Drug: 8M2D

Placebo - healthy participants (Parts I & II combined)

PLACEBO COMPARATOR

Study Parts I and II each include a placebo arm. Part I (SAD) will evaluate up to 5 dose levels of 8M2D. Approximately 30 eligible participants will be enrolled and assigned to 1 of 5 cohorts, with 6 participants per SAD cohort. In each of the SAD cohorts, 6 participants will be randomized in a 4:2 ratio (4 active: 2 placebo) to receive a single SC dose of 8M2D or matching placebo on Day 1. Part II (MAD) will evaluate up to 3 dose levels of 8M2D. Approximately 18 eligible participants will be enrolled and assigned to 1 of 3 cohorts, with 6 participants per MAD cohort. In each of the MAD cohorts, 6 participants will be randomized in a 4:2 ratio (4 active: 2 placebo) to receive once-daily (QD) SC doses of 8M2D or matching placebo on Days 1 to 7. Placebo will be administered by subcutaneous injection.

Drug: Placebo

8M2D Multiple Dose (Open-Label) - Early Alzheimer's Disease - Part III

EXPERIMENTAL

Part III (AD) will consist of a single cohort of participants with early AD. Approximately 6 eligible participants with early AD will be enrolled into a single cohort and will receive QD SC doses of 8M2D from Days 1 to 14. The intervention will be administered by subcutaneous injection.

Drug: 8M2D

Interventions

8M2D DRUG

8M2D administered by subcutaneous injection. Evaluated across single ascending doses (Part I) and multiple ascending doses (Part II) in healthy participants, and as multiple doses in participants with early Alzheimer's disease (Part III).

8M2D Multiple Ascending Dose (MAD) - healthy participants, Part II; 8M2D Multiple Dose (Open-Label) - Early Alzheimer's Disease - Part III; 8M2D Single Ascending Dose (SAD) - healthy participants, Part I

Placebo DRUG

Matching placebo administered by subcutaneous injection in healthy participants across the single ascending dose (Part I) and multiple ascending dose (Part II) parts of the study.

Placebo - healthy participants (Parts I & II combined)

Eligibility Criteria

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

You may qualify if:

• Part I (Single Ascending Dose) and Part II (Multiple Ascending Dose):
• Voluntarily consents to participate in this trial and provides written informed consent before the start of any trial assessments.
• Healthy male and female adults, 18 and 55 years of age (inclusive).
• Participants with a body mass index (BMI) ≥ 18 and ≤ 32 kg/m2 (inclusive) and weigh a minimum of 50 kg.
• Participants with a normal 12-lead ECG at Screening.
• Participant has normal renal function.
• Females participants must meet one of the following criteria:
• a. Females must either be of non-childbearing potential, or if of childbearing potential, must agree to use contraceptives throughout the study period and have a negative pregnancy test at both Screening and Check-in (Day -1).
• Males with a sexual partner who is a female of childbearing potential must be surgically sterile, or agree to use condoms with spermicide or abstain from sexual intercourse, starting from Screening until 90 days after the last dose of the trial medication.
• Participant is willing and able to complete all trial assessments in compliance with the protocol and is able to remain in the inpatient treatment unit for the entire duration of the confinement period and return for outpatient visits.
• Part III Alzheimer's Disease:
• Participant is able to provide written informed consent prior to the performance of any trial -specific procedures.
• Male or female participants with early Alzheimer's disease between 55 and 80 years of age (inclusive) in good health as determined by the Investigator.
• Participants with a BMI of ≥ 18.0 and ≤ 32.0 kg/m2 (inclusive) and weigh a minimum of 50 kg.
• Participants with a 12-lead ECG at screening which, in the opinion of the Investigator, has no abnormalities that compromise participant's safety in this study.

You may not qualify if:

• Part I (Single Ascending Dose) and Part II (Multiple Ascending Dose):
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the participant or the validity of the trial results.
• Participant has abnormal laboratory values detected at Screening or on clinic admission (Day -1) that suggest a clinically significant underlying disease.
• Participant who shows evidence of suicidal ideation as assessed by the C-SSRS at screening and at Day -1 or history of suicide attempt (lifetime).
• Participant with positive serology for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) at Screening.
• Participant smokes cigarettes or uses other nicotine-containing products in the past 3 months prior to Screening.
• Participant with regular alcohol consumption within 6 months prior to the trial defined as an average weekly intake of \> 20 units for males or \> 16 units for females (8g ethanol = 1 unit).
• Participant tests positive in the urine test for alcohol, cotinine, and/or screen for drugs of abuse at the time of screening or Day -1.
• Participant with a history of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM V criteria or later) within the 2 years prior to study entry.
• Participation in any clinical trial and/or recipient of investigational trial medication within 90 days prior to the first dose of 8M2D.
• Participant with a loss of ≥ 500 mL (1 unit) of blood within 90 days prior to receiving the first dose of 8M2D.
• In addition to the above criteria, those judged by the Investigator as not suitable for participating in this clinical trial
• Part III Alzheimer's Disease:
• Participant with history or presence of any uncontrolled systemic disease (e.g., hypertension (systolic BP ≥ 150 mmHg/diastolic BP ≥ 100 mmHg), diabetes mellitus (HbA1c ≥ 8% at the time of screening) etc.).
• Participant with history or presence of unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney, or liver disease.

Sponsors & Collaborators

• Cenna Biosciences Inc.: lead

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Nazneen Dewji, PhD

  Cenna Biosciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly Schafer, MS

CONTACT

619-912-7475; kims@cennabiosciences.com

Study Design

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

Model Details: Phase Ia is a first-in-human, 2-part (Part I single ascending dose and Part II multiple-ascending dose) clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and exploratory immunogenicity of single and multiple doses of 8M2D in healthy participants. Phase Ib will consist of Part III (Alzheimer's Disease \[AD\]), designed to evaluate the safety, tolerability, PK, exploratory immunogenicity, and pharmacodynamics of multiple doses of 8M2D in participants with early AD.

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: May 5, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share