Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants With Prodromal or Mild to Moderate Alzheimer's Disease

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

27 Jun 2024 → ongoing

Decision date (initial)

2024-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-509678-52-00

EudraCT number

2020-002477-98

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Others

To evaluate the safety and tolerability of multiple-ascending dose of RO7126209 (Part 1 and 2), of intravenous dose of RO7126209 (Part 3) and of long-term administration of IV doses (Part 4)
To evaluate the pharmacodynamic (PD) effects of multiple doses of RO7126209 (Part 3)

Secondary objectives 7

1. 1. To evaluate the PD effects of multiple doses (Part 1-2) of RO7126209
2. 2. To evaluate the PD effects of long-term administration of RO7126209 (Part 4)
3. 3. To investigate the multiple (Part 1-4) and single (Part 3) IV dose pharmacokinetics of RO7126209 in plasma
4. 4. To investigate the pharmacokinetics and CSF penetration of a selected dose of RO7126209 in plasma (Part 4)
5. 5. To investigate the CSF penetration after multiple doses of RO7126209 (Part 1-3)
6. 6. To evaluate the immunogenicity of single (Part 3) and multiple doses (Part 1-3) of RO7126209
7. 7. To evaluate the immunogenicity of long-term administration of RO7126209 (Part 4)

Conditions and MedDRA coding

Alzheimer's disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Age 50 to 85 years (inclusive) at screening
2. 2. Probable mild to moderate AD dementia (consistent with NIA-AA core clinical criteria for probable AD dementia) (McKhann et al 2011) or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD) (Albert et al 2011)
3. 3. Mini-Mental State Examination (MMSE) score of 18 to 28 points, inclusive, within 84 days before baseline
4. 4. Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 84 days before baseline
5. 5. Positive amyloid PET scan (cut-off: > 50 Centiloid units) within 12 months before baseline
6. 6. In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least 8 weeks prior to baseline and until randomization

Exclusion criteria 6

1. 1. Any condition other than AD that may affect cognition
2. 2. Significant cerebral abnormalities
3. 3. History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition
4. 4. History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder, Cancer, unless cured or currently not needing treatment. Note: History of major depression is acceptable, if participant has had no episode within the past year, or is considered in remission, or depression is controlled by treatment
5. 5. History of any clinically significant hematological diseases, clinically significant ophthalmologic disease or chronic kidney disease
6. 6. Atrial fibrillation, cardiovascular disease or uncontrolled hypertension

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Nature, frequency, severity, and timing of AEs, including – for Part 1 only – DLAEs. Significant assessments reported as AEs include clinical laboratory assessments and vital signs, physical and neurological examination, 12-lead ECG, and brain MRI findings (including the occurrence of vasogenic edema and hemorrhage) (Part 1-4)
2. 2. Change from baseline in brain amyloid load, as measured by amyloid PET scan (Part 3)

Secondary endpoints 4

1. 1. Change from baseline in brain amyloid load, as measured by amyloid PET scan (Part 1, 2 and 4 only)
2. 2. Plasma Concentration of RO7126209 at specified timepoints
3. 3. CSF concentration of RO7126209
4. 4. Incidence and titer of anti-RO7126209 ADAs over time

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

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 8

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

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

Documents 67 files

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

Application history

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