A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7812653 in Participants With Early Symptomatic Alzheimer's Disease (eAD)

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7812653 Following Intrathecal Administration in Participants With Early Symptomatic Alzheimer's Disease

This study aims to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics following administration of RO7812653 in participants with eAD.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: RO7812653; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP45770 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Recruiting
      • Brain Research Center Amsterdam
• Spain
  • Córdoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia
• Sweden
  • Mlndal, Sweden, 43180
    • Recruiting
    • Sahlgrenska Universitetssjukhuset
  • Solna, Sweden, 171 76
    • Recruiting
    • Karolinska Universitetssjukhuset
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • National Hospital For Neurology and Neurosurgery
  • Greater London
    • London, Greater London, United Kingdom, SE5 8AF
      • Recruiting
      • Institute of Psychiatry, Psychology and Neuroscience;Department of Old Age Psychiatry
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • Southampton General Hospital
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G21 3UW
      • Recruiting
      • Queen Elizabeth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Probable AD dementia (consistent with National Institute on Aging and Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia) [McKhann et al 2011] or Mild Cognitive Impairment (MCI) due to AD (consistent with the NIA-AA core clinical criteria for mild cognitive impairment due to AD) [Albert et al 2011]).
• Willingness and ability to complete all aspects of the study. The participant should be capable of completing assessments either alone or with the help of the study partner.
• Fluency in the language of the tests used at the study site.
• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eyewear and hearing aids are permitted).
• If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 8 weeks prior to screening and until randomization is required.
• Agreement not to participate in other research studies for the duration of this study.

Exclusion Criteria:

• Any medical history or evidence of a condition other than AD that may affect cognition.
• Presence of any significant cerebral abnormalities that would contraindicate lumbar puncture, as assessed on MRI
• Any other significant cerebral abnormalities that the Investigator considers clinically significant
• History of schizophrenia, schizoaffective disorder, major depression or bipolar disorder.'
• Presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological medical conditions which are not stable and adequately controlled or which in the opinion of the investigator could affect the subject's safety in the study or interfere with the study assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7812653; Participants will receive a dose of RO7812653	Drug: RO7812653; Participants will receive RO7812653 as per the schedule in the protocol
Placebo Comparator: Placebo; Participants will receive a dose of placebo	Drug: Placebo; Participants will receive placebo as per the schedule in the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Adverse Events		Up to approximately 40 weeks
Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores	C-SSRS measures 4 constructs as follows: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories. Numeric ratings are provided for intensity of ideation (if present), from 1 to 5, with 1 being the least severe and 5 being the most severe.	Up to approximately 40 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of RO7812653	Up to approximately 40 weeks
Cerebral Spinal Fluid (CSF) Concentration of RO7812653	Up to approximately 40 weeks
Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7812653	Up to approximately 40 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): April 19, 2028
• Study Completion (Estimated): March 5, 2030

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: BP45770; 2025-522101-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No