2-Hydroxybenzylamine (2-HOBA) Study in Early Alzheimer's Patients

NCT06432166 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MTI2024-CS01RC-201910-2019696IRB 231544
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators propose a phase 1b/2a, randomized, double-blind, placebo-controlled, parallel group dose finding and biomarker study to evaluate the safety, tolerability, and biomarker activity of 2-HOBA in 48 MCI/AD participants. Participants will be randomized 1:1:1:1 to receive 250, 500, 750 mg 2-HOBA acetate TID or placebo for 16 weeks. Blood and cerebral spinal fluid (CSF) will be collected to measure markers of protein modification by dicarbonyls (IsoLGs- \& MDA), pTau-181, YKL-40, and NF-L.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Mild Cognitive Impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Safety/Tolerability (adverse events)

  Rates of adverse events will be compared between active and placebo arms and presented as summary statistics.

  Baseline to week 16

• Change in dicarbonyl protein adducts

  Change in CSF levels of the dilysyl-malondialdehyde crosslink and the lysyl-levuglandin adduct of CSF proteins in a dose-responsive relationship

  Baseline to week 16

Secondary Outcomes (6)

• Compliance

  Baseline to week 16

• Measurement of biomarker, p-Tau181

  Baseline to week 16

• Measurement biomarker, human cartilage glycoprotein 39 (YKL-4)

  Baseline to week 16

• Measurment of biomarker, neurofilaments light chain protein (NF-L)

  Baseline to week 16

• Measurement of biomarker, F2-Isoprostanes

  Baseline to week 16

Other Outcomes (3)

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  Baseline to Week 16

• Activities of Daily Living (ADL)

  Baseline to Week 16

• Quantitative Electroencephalography (EEG)

  Baseline to Week 16

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo treatment TID for 16 weeks.

Other: Placebo

250 mg 2-HOBA acetate

ACTIVE COMPARATOR

250 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Drug: 2-hydroxybenzylamine acetate

500 mg 2-HOBA acetate

ACTIVE COMPARATOR

500 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Drug: 2-hydroxybenzylamine acetate

750 mg 2-HOBA acetate

ACTIVE COMPARATOR

750 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Drug: 2-hydroxybenzylamine acetate

Interventions

2-hydroxybenzylamine acetate DRUG

2-hydroxybenzylamine acetate (2-HOBA) is taken three times per day for 16 weeks

Also known as: 2-HOBA

250 mg 2-HOBA acetate; 500 mg 2-HOBA acetate; 750 mg 2-HOBA acetate

Placebo OTHER

Placebo taken three times per day for 16 weeks.

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MCI due to AD:
• Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent.
• Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
• Mini-Mental State Exam31 score between 24 and 30, inclusive
• Clinical Dementia Rating (CDR)32 Global = 0.5. Memory Box score must be at least 0.5.
• Mild AD:
• Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent.
• Mild dementia of the Alzheimer's type according to the NIA-AA 2018 criteria.
• CDR global score of 0.5 and CDR of 0.5 or more in at least one of the three instrumental activities of daily living categories (personal care, home \& hobbies, community affairs) Or CDR global score of 1.0
• MMSE ≥20
• Age 55-85 (inclusive)
• Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised:
• Less than or equal to 11 for 16 or more years of education
• Less than or equal to 9 for 8 - 15 years of education
• Less than or equal to 6 for 0 - 7 years of education

You may not qualify if:

• Any other significant neurologic disease including Parkinson's disease, multi- infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
• Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation, or behavioral problems within 3 months, which could lead to difficulty complying with the protocol.
• History of schizophrenia (DSM V criteria).
• History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria).
• Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic (Class C defined by Child-Pugh criteria), endocrine, or other systemic disease in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
• Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment.
• Clinically significant abnormalities in screening laboratories or ECG.
• Residence in a skilled nursing facility.
• Use of any excluded medication as described in Section 6.10, including:
• Use centrally acting anti-cholinergic drugs.
• Use of any investigational drugs within 4 weeks or 5 half-lives, whichever is longer, prior to screening.
• A current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening.
• Contraindications for MRI studies, including claustrophobia, the presence of metal(ferromagnetic) implants, or cardiac pacemaker.
• Participants whom the Site PI deems to be otherwise ineligible.

Sponsors & Collaborators

• MTI Biotech Inc: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

Center for Cognitive Medicine, Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

2-(aminomethyl)phenol

Condition Hierarchy (Ancestors)

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

Study Officials

• Paul Newhouse, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• John A. Rathmacher, Ph.D.

  MTI Biotech Inc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John A. Rathmacher, Ph.D.

CONTACT

515-296-9916; rathmacher@mtibiotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Treatment will be supplied in capsules of the same size and color.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A phase 1b/2a, randomized, double-blind, placebo-controlled, parallel group dose finding and biomarker study.

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 29, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 8, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)