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

• ClinicalTrials.gov Identifier: NCT04639050
• Recruitment Status: Recruiting
• First Posted: November 20, 2020
• Last Update Posted: May 15, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Alzheimers Disease	Drug: RO7126209; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: January 31, 2025
• Estimated Study Completion Date: January 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: Dose Level 1 of RO7126209; Participants will receive multiple doses of RO7126209 at dose level 1 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period.	Drug: RO7126209; RO7126209 will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Placebo Comparator: Cohort 1: Placebo; Participants will receive matching placebo to dose level 1 Q4W for 28 weeks followed by a 28-week safety follow-up period.	Drug: Placebo; Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.; Other Name: RO727-5887, F01-01
Experimental: Cohort 2: Dose Level 2 of RO7126209; Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: RO7126209; RO7126209 will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Placebo Comparator: Cohort 2: Placebo; Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: Placebo; Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.; Other Name: RO727-5887, F01-01
Experimental: Cohort 3: Dose Level 3 of RO7126209; Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: RO7126209; RO7126209 will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Placebo Comparator: Cohort 3: Placebo; Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: Placebo; Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.; Other Name: RO727-5887, F01-01
Experimental: Cohort 4: Dose Level 4 of RO7126209; Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: RO7126209; RO7126209 will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Placebo Comparator: Cohort 4: Placebo; Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.	Drug: Placebo; Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.; Other Name: RO727-5887, F01-01

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Adverse Events (AEs), Including Dose-Limiting Adverse Events (DLAEs) [ Time Frame: Up to 56 weeks ]

Secondary Outcome Measures :

1. Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Week 12 (Cohorts 3 and 4 only), Week 28 ]
2. Plasma Concentration of RO7126209 [ Time Frame: Up to 32 weeks ]
3. Cerebral Spinal Fluid (CSF) Concentration of RO7126209 [ Time Frame: Baseline, Week 25 ]
4. Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209 [ Time Frame: Up to 56 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key inclusion criteria:

• 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

Key exclusion criteria:

• 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

Contacts and Locations

Contacts

Contact: Reference Study ID Number: BP42155 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Locations

United States, Florida

JEM Research LLC; Active, not recruiting

Atlantis, Florida, United States, 33462

Brain Matters Research, Inc.; Withdrawn

Delray Beach, Florida, United States, 33445

Progressive Medical Research; Withdrawn

Port Orange, Florida, United States, 32127

United States, Michigan

Quest Research Institute; Recruiting

Farmington Hills, Michigan, United States, 48334

United States, Pennsylvania

Abington Neurological Associates; Completed

Abington, Pennsylvania, United States, 19001

United States, Texas

Kerwin Research Center, LLC; Recruiting

Dallas, Texas, United States, 75231

Australia, Victoria

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre; Recruiting

Heidelberg West, Victoria, Australia, 3081

Alfred Hospital; Department of Neurology; Recruiting

Melbourne, Victoria, Australia, 3004

Poland

Osrodek Badan Klinicznych Euromedis; Recruiting

Szczecin, Poland, 70-111

NZOZ WCA; Recruiting

Wroc?aw, Poland, 53-659

Spain

Hospital General De Catalunya; Servicio de Neurologia; Recruiting

Sant Cugat del Valles, Barcelona, Spain, 8195

Fundación ACE; Servicio de Neurología; Active, not recruiting

Barcelona, Spain, 08028

Hospital Clinic i Provincial; Servicio de Neurologia; Completed

Barcelona, Spain, 08036

Hospital Universitario Dr. Peset; Servicio de Neurologia; Recruiting

Valencia, Spain, 46017

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04639050
• Other Study ID Numbers: BP42155; 2020-002477-98 ( EudraCT Number )
• First Posted: November 20, 2020
• Last Update Posted: May 15, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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