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

28 avril 2026 mis à jour par: Cenna Biosciences Inc.

A Phase Ia (SAD/MAD), Randomized, Double-Blind, Placebo-Controlled Trial and Phase Ib Open-Label Trial to Evaluate Safety, Tolerability, PK, and Exploratory Immunogenicity of Single and Multiple Doses of 8M2D in Healthy Participants and Early AD Participants.

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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Description détaillée

Trial Rationale: This is a three-part Phase 1a/b clinical trial. Phase Ia is a first-in-human (FIH), 2-part (Part I [SAD] and Part II [MAD]) clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), 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 (PD) of multiple doses of 8M2D in participants with early AD.

Data from this trial will be used to identify doses of 8M2D that show safety and tolerability and PD effects on amyloid beta (Aβ), to aid in the design of future trials in patients with AD. Prior to this trial, 8M2D has not been administered to humans. Safety and tolerability evaluations will be conducted over a range of single and multiple doses of 8M2D and dose escalation will not proceed until safety and tolerability data and PK parameters from previous doses have been reviewed by an independent Data and Safety Monitoring Board (DSMB).

This trial will aim to assess a maximum-tolerated dose (MTD), or a maximum feasible dose (based on tolerability of the subcutaneous [SC] injections), or a maximum pharmacologically active dose, based on safety, tolerability and PK data as well as on model-based prediction of the anticipated Aβ lowering. The data generated in this trial will be used to help design subsequent clinical trials in participants with early AD.

Type d'étude

Interventionnel

Inscription (Estimé)

54

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Oui

La description

Inclusion Criteria:

Part I (Single Ascending Dose) and Part II (Multiple Ascending Dose):

  1. Voluntarily consents to participate in this trial and provides written informed consent before the start of any trial assessments.
  2. Healthy male and female adults, 18 and 55 years of age (inclusive).
  3. Participants with a body mass index (BMI) ≥ 18 and ≤ 32 kg/m2 (inclusive) and weigh a minimum of 50 kg.
  4. Participants with a normal 12-lead ECG at Screening.
  5. Participant has normal renal function.
  6. 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).

  7. 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.
  8. 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:

  1. Participant is able to provide written informed consent prior to the performance of any trial -specific procedures.
  2. 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.
  3. Participants with a BMI of ≥ 18.0 and ≤ 32.0 kg/m2 (inclusive) and weigh a minimum of 50 kg.
  4. 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.
  5. 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).

  6. 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.
  7. 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.
  8. Participant meets the diagnostic criteria of mild cognitive impairment (MCI) of probable Alzheimer's disease consistent with National Institute On Aging - Alzheimer's Association (NIA-AA) research framework.
  9. Participant with a qualifying amyloid score.
  10. Participant with a Mini-Mental State Examination (MMSE) score between 20 and 28 inclusive at screening and baseline.

Exclusion Criteria:

Part I (Single Ascending Dose) and Part II (Multiple Ascending Dose):

  1. 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.
  2. Participant has abnormal laboratory values detected at Screening or on clinic admission (Day -1) that suggest a clinically significant underlying disease.
  3. 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).
  4. 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.
  5. Participant smokes cigarettes or uses other nicotine-containing products in the past 3 months prior to Screening.
  6. 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).
  7. 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.
  8. 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.
  9. Participation in any clinical trial and/or recipient of investigational trial medication within 90 days prior to the first dose of 8M2D.
  10. Participant with a loss of ≥ 500 mL (1 unit) of blood within 90 days prior to receiving the first dose of 8M2D.
  11. 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:

  1. 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.).
  2. Participant with history or presence of unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney, or liver disease.
  3. Participant with any active or unstable clinically significant medical or psychiatric condition as judged by the Investigator.
  4. Participant who has current serious or unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the Investigator's opinion, could interfere with the analyses of safety and efficacy in this trial.
  5. Participant with any evidence of a condition other than AD that may affect cognition such as other dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or infections with neurological sequelae.
  6. Participant with history within the past 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate specific antigen post-resection.
  7. Participant with history of intracranial hemorrhage, cerebrovascular aneurysm, or arteriovenous malformation, carotid artery occlusion, stroke, or epilepsy.
  8. 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).
  9. Participant with positive serology for HBsAg, HBcAb, HCV, or HIV at Screening.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 8M2D Single Ascending Dose (SAD) - healthy participants, Part I

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.

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

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.

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).
Comparateur placebo: Placebo - healthy participants (Parts I & II combined)

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.

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

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of participants reporting treatment-emergent adverse events
Délai: Baseline to Day 44
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
Délai: Baseline to Day 14
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
Délai: Baseline to Day 22
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
Délai: Baseline to Day 14
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
Délai: Baseline to Day 22
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
Délai: Baseline to Day 15
Evaluation of 12-lead ECG parameters.
Baseline to Day 15
Number of participants demonstrating adverse changes in physical and/or neurologic examinations
Délai: Baseline to Day 22
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
Délai: Baseline to Day 22
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
Délai: Baseline to Day 14
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
Délai: Baseline to Day 14
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
Délai: Baseline to Day 14
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)
Délai: Baseline to Day 14
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)
Délai: Baseline to Day 14
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
Délai: Baseline to Day 14
Evaluation of biomarkers of AD through plasma and CSF collected from all participants in Part III (AD) of the study.
Baseline to Day 14

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Assessment of the presence of anti-8M2D antibody in participants of all cohorts.
Délai: Baseline to Day 22
Evaluation of anti-8M2D antibody presence in blood samples collected from all participants.
Baseline to Day 22

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Nazneen Dewji, PhD, Cenna Biosciences

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

15 septembre 2026

Achèvement primaire (Estimé)

1 septembre 2027

Achèvement de l'étude (Estimé)

1 décembre 2027

Dates d'inscription aux études

Première soumission

20 avril 2026

Première soumission répondant aux critères de contrôle qualité

28 avril 2026

Première publication (Réel)

5 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

5 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 avril 2026

Dernière vérification

1 avril 2026

Plus d'information

Termes liés à cette étude

Plan pour les données individuelles des participants (IPD)

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Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

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Étudie un produit d'appareil réglementé par la FDA américaine

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produit fabriqué et exporté des États-Unis.

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Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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