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

Alzheimers Disease Clinical Trial

Official title:

A Phase Ib/IIa, Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Patients With Prodromal or Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04639050
• Other study ID #: BP42155
• Secondary ID: 2020-002477-9820
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 15, 2021
• Est. completion date: September 30, 2027

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP42155 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of multiple-ascending intravenous (IV) doses of RO7126209 in participants with prodromal or mild to moderate Alzheimer's disease (AD), who are amyloid positive based on amyloid positron emission tomography (PET) scan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 285
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Key inclusion criteria for part 1, 2 and 3:

• Ability to provide written consent signed by the participant

• Availability of a person (referred to as the "study partner") who: consents to participate throughout the duration of study, in the Investigator's judgment, has frequent and sufficient contact with the participant, is fluent in the language of the tests used at the study site

• Willingness and ability to complete all aspects of the study (including magnetic resonance imaging [MRI], lumbar puncture, clinical genotyping, and positron emission tomography [PET] imaging)

• Capable of completing assessments either alone or with the help of the study partner

• Adequate visual and auditory acuity, in the Investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)

• Probable mild to moderate AD dementia (consistent with National Institute on Aging-Alzheimer's Association [NIA-AA] core clinical criteria for probable AD dementia) or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)

• Screening Mini-Mental State Examination (MMSE) score of 18 to 28 points, inclusive, within 84 days before baseline

• Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 84 days before baseline

• Positive amyloid PET scan (cut-off: >50 Centiloid units) within 12 months before baseline

• In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least 8 weeks prior to baseline and until randomization

• Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug

• Agreement not to participate in other research studies for the duration of this study

• Agree to apolipoprotein E (APOE) genotyping

Inclusion criteria for Part 4:

• Completed the treatment period in Part 1, Part 2, or Part 3 of the study

Key exclusion criteria for part 1, 2 and 3:

• Any evidence of other relevant neurological condition, including other (non-AD) neurodegenerative and neuropsychiatric conditions, neurovascular brain disorders, seizure disorders, inflammatory and infectious disorders of the central nervous system, trauma and delirium, among several others

• Other relevant medical conditions including significant hematological diseases, any clinically significant ophthalmologic diseases, decreased visual acuity in either eye, with a BCVA letter score of less than 20 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or the Snellen equivalent of 20/400 if the ETDRS chart is not used

• Clinically significant cardiovascular diseases, chronic kidney disease, confirmed and unexplained impaired hepatic function, abnormal thyroid function, among several others

• History of hypersensitivity to biologic agents or any of the excipients in the formulation

• Clinically significant abnormalities (as judged by the Investigator) in laboratory test results (including complete blood count, chemistry panel, routine cerebrospinal fluid [CSF] parameters and urinalysis)

• MRI exclusion criteria: >2 lacunar infarcts, any territorial infarct >1 cm^3, any white matter lesion that corresponds to an overall Fazekas score of 3 that requires at least one confluent hyperintense lesion on the fluid-attenuated inversion recovery (FLAIR) sequence, which is =20 mm in any dimension

• Combined number of microhemorrhages and focal areas of leptomeningeal hemosiderosis (i.e., cumulative amyloid-related imaging abnormality-microhemorrhage/hemosiderin deposition [ARIA-H]) on MRI more than 5 (and should not include more than 3 focal areas of leptomeningeal hemosiderosis) based on the review performed by the central MRI reader prior to randomization

• Presence of any other significant cerebral abnormalities, including amyloid-related imaging abnormality-edema/effusion (ARIA-E), as assessed on MRI

• Inability to tolerate MRI procedures or contraindication to MRI

• Inability to undergo ophthalmological assessments

• Contraindication to lumbar puncture

• Contraindication to having a PET scan

Exclusion criteria for Part 4:

• Prematurely discontinued from the treatment period for study (i.e., before the start of the follow-up period of Part 1, Part 2, or Part 3) for any reason or meeting discontinuation criteria before the baseline visit of Part 4.

• Received any active investigational treatment other than RO7126209 during or since completion of Part 1, Part 2 or Part 3

• Any passive immunotherapy (immunoglobulin) since completion of Part 1, Part 2, or Part 3 that is meant to prevent or postpone cognitive decline.

• Use of anti-coagulation medications - Evidence of ongoing ARIA-E. In this case participant may enroll into Part 4 once the ARIA-E is resolved - Evidence of ongoing infusion-related reaction (IRR) or hypersensitivity reaction. In this case participant may enroll into Part 4 once the IRR is resolved.

• Any drop in hemoglobin of > 20% compared to predose on Day 1 or hemoglobin value below 10 g/dL

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimers Disease

Intervention

Drug:
• RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
• Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Locations

Country	Name	City	State
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	Alfred Hospital; Department of Neurology	Melbourne	Victoria
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	Toronto Memory Program	Toronto	Ontario
Chile	Centro de Investigación Clínica UC-CICUC	Santiago
Chile	Hospital Clinico Univ de Chile	Santiago
Japan	Yokohama City Minato Red Cross Hospital	Kanagawa
Japan	Koseikai Takeda Hospital	Kyoto
Japan	National Hospital Organization Utano National Hospital; Neurology	Kyoto
Japan	Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital	Tokyo
Japan	Keio University Hospital; Neurology	Tokyo
Japan	Tokyo Metropolitan Geriatric Hospital	Tokyo
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Samsung Medical Center	Seoul
Poland	Vitamed Ga?aj i Cichomski Spó?ka Jawna	Bydgoszcz
Poland	Clinical Research Center Sp. z o.o. MEDIC-R Spó?ka Komandytowa	Pozna?
Poland	Osrodek Badan Klinicznych Euromedis	Szczecin
Poland	NZOZ WCA	Wroc?aw
Spain	Fundación ACE; Servicio de Neurología	Barcelona
Spain	Hospital Clinic i Provincial; Servicio de Neurologia	Barcelona
Spain	Policlínica Guipuzcoa; Servicio de Neurología	Donostia-san Sebastian	Guipuzcoa
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona
Spain	Hospital Universitario Dr. Peset; Servicio de Neurologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
United Kingdom	Re-Cognition	Birmingham
United Kingdom	Recognition Health Bristol	Bristol
United Kingdom	RE:Cognition Health	London
United Kingdom	UCL Institute of Neurology; QSMSC, RSH	London
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	JEM Research LLC	Atlantis	Florida
United States	K2 Medical Research-Winter Garden	Clermont	Florida
United States	Columbus Memory Center	Columbus	Georgia
United States	Kerwin Research Center, LLC	Dallas	Texas
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Center for Advanced Research & Education	Gainesville	Georgia
United States	K2 Medical Research - The Villages	Lady Lake	Florida
United States	K2 Medical Research, LLC	Maitland	Florida
United States	Alzheimer's Memory Center	Matthews	North Carolina
United States	Optimus U Corp	Miami	Florida
United States	Advent Health Orlando	Orlando	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	Alzheimer's Research and Treatment Center	Stuart	Florida
United States	Charter Research - Lady Lake/The Villages	The Villages	Florida
United States	Alzheimer?s Research and Treatment Center	Wellington	Florida
United States	Charter Research - Winter Park/Orlando	Winter Park	Florida
United States	Conquest Research, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Japan,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs)		Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks
Primary	Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan		Up to approximately 24 weeks
Secondary	Part 1, 2, and 4: Change From Baseline in Brain Amyloid Load as Measured by Amyloid PET Scan		Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 101 weeks
Secondary	Part 1, 2, 3, and 4: Plasma Concentration of RO7126209		Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 105 weeks
Secondary	Part 1, 2, 3, and 4: Cerebral Spinal Fluid (CSF) Concentration of RO7126209		Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 101 weeks
Secondary	Part 1, 2, 3, and 4: Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209		Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks