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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04639050




Registration number
NCT04639050
Ethics application status
Date submitted
17/11/2020
Date registered
20/11/2020

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-002477-98
Secondary ID [2] 0 0
BP42155
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimers Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO7126209
Treatment: Drugs - Placebo

Experimental: Part 1 (Dose Finding) 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.

Placebo comparator: Part 1 (Dose Finding) 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.

Experimental: Part 1 (Dose Finding) 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.

Placebo comparator: Part 1 (Dose Finding) 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.

Experimental: Part 1 (Dose Finding) 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.

Placebo comparator: Part 1 (Dose Finding) 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.

Experimental: Part 1 (Dose Finding) 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.

Placebo comparator: Part 1 (Dose Finding) 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.

Experimental: Part 1 (Dose Finding) Cohort 5: Dose Level 5 of RO7126209 - Participants will receive a total of 2 doses of RO7126209 at dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Placebo comparator: Part 1 (Dose Finding) Cohort 5: Placebo - Participants will receive a total of 2 doses of matching placebo to dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Experimental: Part 2 (Expansion) Cohort 1: Dose Level 1 of RO7126209 - Participants will receive multiple doses of RO7126209 at dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Placebo comparator: Part 2 (Expansion) 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.

Experimental: Part 2 (Expansion) 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.

Placebo comparator: Part 2 (Expansion) 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.

Experimental: Part 2 (Expansion) Cohort 3: Dose Level 3 of RO7126209 - Participants will receive a total of 2 doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Placebo comparator: Part 2 (Expansion) Cohort 3: Placebo - Participants will receive a total of 2 doses of matching placebo to dose level 3, Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Experimental: Part 3 (Dose/Frequency/Pharmacodynamic (PD) Relationship): Dose Level 1: RO7126209 - Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 1, Q4W, for 24 weeks followed by a 28-week safety follow-up period.

Experimental: Part 3 Dose/Frequency/PD Relationship: Dose Level 2: RO7126209 - Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 2, Q12W, for 24 weeks followed by a 28-week safety follow-up period.

Experimental: Part 4: Open Label Extension (OLE) phase Arm 1: RO7126209 - Participants who completed Part 1, 2, or 3 and have reached amyloid negativity (= 24 centiloids) in either of the Study Parts or at the OLE baseline visit will receive RO7126209 Q12W for 101 weeks. The dose level will depend on the dose level in Part 1, 2, and 3.

Experimental: Part 4 OLE Phase Arm 2: RO7126209 - Participants who completed Part 1, 2, or 3 and who are amyloid positive (=24 centiloids) will receive RO7126209 Q4W for 12 weeks and will have to reach amyloid negativity (= 24 centiloids) before they can switch to Q12W dosing in an open-label treatment period of 89 weeks. The dose level will depend on the dose level received in Part 1,2, and 3.

Experimental: Part 4 OLE Phase Arm 3: RO7126209 - Participants who completed Part 1, 2, or 3 and who are amyloid positive (=24 centiloids) at week 12 of OLE will receive RO7126209 Q4W for an additional 12 weeks, before to switch to Q12W dosing for the remaining 77 weeks in an open-label treatment period. The dose level will depend on the dose level received in Part 1,2, and 3.


Treatment: Drugs: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.

Treatment: Drugs: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks
Primary outcome [2] 0 0
Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan
Timepoint [2] 0 0
Up to approximately 24 weeks
Secondary outcome [1] 0 0
Part 1, 2, and 4: Change From Baseline in Brain Amyloid Load as Measured by Amyloid PET Scan
Timepoint [1] 0 0
Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 101 weeks
Secondary outcome [2] 0 0
Part 1, 2, 3, and 4: Plasma Concentration of RO7126209
Timepoint [2] 0 0
Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 105 weeks
Secondary outcome [3] 0 0
Part 1, 2, 3, and 4: Cerebral Spinal Fluid (CSF) Concentration of RO7126209
Timepoint [3] 0 0
Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 101 weeks
Secondary outcome [4] 0 0
Part 1, 2, 3, and 4: Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209
Timepoint [4] 0 0
Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks

Eligibility
Key inclusion criteria
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
* More than 4 microhemorrhages on MRI and/or presence of any focal area 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
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.
* MRI evidence of any of the following at OLE baseline: evidence of ongoing ARIA-E, any ARIA-H (leptomeningeal hemosiderosis or microhemorrhages) that would require permanent discontinuation of study treatment, > 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 FLAIR sequence, which is = 20 mm in any dimension
* Any drop in hemoglobin of > 20% compared to predose on Day 1 or hemoglobin value below 10 g/dL

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2028
Actual
Sample size
Target
285
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [2] 0 0
Alfred Hospital; Department of Neurology - Melbourne
Recruitment postcode(s) [1] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
British Columbia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Chile
State/province [10] 0 0
Santiago
Country [11] 0 0
Japan
State/province [11] 0 0
Kanagawa
Country [12] 0 0
Japan
State/province [12] 0 0
Kyoto
Country [13] 0 0
Japan
State/province [13] 0 0
Tokyo
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Incheon
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Poland
State/province [16] 0 0
Bydgoszcz
Country [17] 0 0
Poland
State/province [17] 0 0
Pozna?
Country [18] 0 0
Poland
State/province [18] 0 0
Szczecin
Country [19] 0 0
Poland
State/province [19] 0 0
Wroc?aw
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Guipuzcoa
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Birmingham
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Bristol
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BP42155 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04639050