A study to evaluate the safety and long-term biomarker effects of RO7269162 in participants at risk for or at the prodromal stage of Alzheimer’s Disease (AD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

29 Mar 2024 → ongoing

Decision date (initial)

2024-03-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety

1. To investigate the safety and tolerability of daily oral dosing of RO7269162 and to assess the effect of daily oral dosing of RO7269162 on brain amyloid accumulation

Secondary objectives 2

1. 1. To assess the effect of daily oral dosing of RO7269162 on pharmacodynamic (PD) biomarkers related to Aβ metabolism in CSF and plasma
2. 2. To investigate the pharmacokinetic (PK) of daily oral dosing of RO7269162 (and its metabolite[s] as appropriate) in plasma and CSF

Conditions and MedDRA coding

Alzheimer’s Disease

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Body Mass Index (BMI) between 18 to 35 kg/m2 inclusive, at screening
2. 2. Participants must be either cognitively unimpaired or with a diagnosis of MCI due to AD, according to the NIA – AA workgroups on diagnostic guidelines for AD, and/or according to the updated NIA-AA research framework
3. 3. Clinical Dementia Rating-Global Score (CDR-GS) of 0 or 0.5
4. 4. Positive amyloid PET scan based on a cut-off of ≥24 CL units
5. 5. Availability of a person (referred as a “study partner” throughout the protocol) who: (a) has frequent and sufficient contact (e.g., minimum twice a week in-person, via telephone, video calls, by e-mail or other electronic means) with the participant, and is willing and able to provide accurate information regarding the participant’s cognitive and functional abilities, signs the necessary ICF(s), and has sufficient cognitive capacity to accurately report on the participant’s cognitive and functional abilities; (b) is in sufficient good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the duration of the study; and (c) is fluent in the language of the tests used at the study site. Please note that the study partner does not need to be a family member. Every effort should be made to keep the same study partner throughout the study.
6. 6. In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least eight weeks prior to first IMP intake

Exclusion criteria 6

1. 1. Any medical history or evidence of a condition other than AD that may affect cognition
2. 2. History or presence of significant cardiovascular conditions and/or significant hematological disease
3. 3. History or presence of chronic kidney disease and/or impaired hepatic function
4. 4. Uncontrolled/poorly controlled diabetes
5. 5. History of or activate inflammatory bowel disease
6. 6. Have received any passive or active immunotherapy (immunoglobulin) or other long-acting biologic agent that is under evaluation or approved to prevent or postpone cognitive decline administered within 1 year prior to first IMP intake, and/or any other investigational treatment within five half-lives or 16 weeks prior to screening, whichever is longer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Nature, incidence, severity, and outcome of AEs
2. 2. Changes from baseline in vital signs, ECG parameters, Columbia-Suicide Severity Rating Scale (C-SSRS) and safety laboratory findings
3. 3. Change from baseline in brain amyloid load, as measured by amyloid PET scan

Secondary endpoints 3

1. 1. Change from baseline in Aβ37, Aβ38, Aβ40 and Aβ42 in CSF and Aβ40 and Aβ42 in plasma
2. 2. Plasma concentrations of RO7269162 (and its metabolite[s] as appropriate)
3. 3. CSF concentrations of RO7269162 (and its metabolite[s] as appropriate)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 9

Locations

6 EU/EEA countries · 44 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications