What is the mechanism of action of this treatment?

The most common treatments for Alzheimer's Disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and amyloid-targeting therapies. Cholinesterase inhibitors work by increasing cholinergic transmission, providing modest symptomatic relief in cognition and global functioning. Amyloid-targeting therapies, such as monoclonal antibodies (e.g., aducanumab), aim to reduce amyloid-beta plaques in the brain, which are believed to play a key role in AD pathogenesis. These treatments are significant for AD patients as they offer potential disease-modifying effects, potentially slowing disease progression and improving quality of life.

What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease that target amyloid plaques, such as aducanumab, often have side effects including amyloid-related imaging abnormalities (ARIA), which can manifest as brain swelling or microhemorrhages. Other reported side effects include headache, falls, diarrhea, confusion, and hypersensitivity reactions like angioedema and urticaria. These treatments may also lead to the development of antibodies against the drug. Additionally, cholinesterase inhibitors, another class of Alzheimer's treatments, can cause gastrointestinal issues, muscle cramps, and insomnia.

What prior FDA approvals exist?

The FDA has approved several treatments for Alzheimer's Disease that target amyloid plaques to modify disease progression. Notably, aducanumab (Aduhelm) was approved in 2021 as the first therapy to reduce amyloid-beta plaques in the brain, which are believed to play a central role in Alzheimer's pathology. Another drug, lecanemab (Leqembi), received accelerated approval in 2023 for its ability to target and clear amyloid plaques. These treatments aim to slow the progression of Alzheimer's by addressing one of its core pathological features.

What other types of research exist?

Promising alternatives to RO7126209 for Alzheimer's Disease treatment include therapies targeting Tau protein. These approaches involve blocking Tau aggregation, inhibiting Tau phosphorylation, using microtubule-stabilizing agents, and enhancing Tau degradation pathways. These strategies aim to reduce Tau-mediated neurodegeneration, offering a novel and potentially more effective treatment avenue.

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Monoclonal Antibodies

RO7126209 for Alzheimer's Disease

Phase 1 & 2

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Probable mild to moderate Alzheimer's Disease (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)

Adequate visual and auditory acuity, sufficient to perform neuropsychological testing

Must not have

Contraindication to lumbar puncture

Any evidence of other relevant neurological condition

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial is testing a drug called RO7126209 in people with early to moderate Alzheimer's disease. The goal is to see if the drug is safe, effective, and how the body processes it.

Who is the study for?

This trial is for people with early or moderate Alzheimer's who can perform tests with a study partner's help. They must have stable Alzheimer's medication use, good vision and hearing for testing, an MMSE score of 18-28, and a positive amyloid PET scan. Those with other neurological conditions or significant medical issues, MRI contraindications, or hypersensitivity to biologic agents cannot join.

What is being tested?

The trial is testing RO7126209 via IV against a placebo in those with mild to moderate Alzheimer's. It aims to assess the drug’s safety and effects on the body (pharmacokinetics) and its impact on the disease (pharmacodynamics), including how well it is tolerated by patients over multiple doses.

What are the potential side effects?

Potential side effects are not specified but may include reactions related to IV infusion, immune responses due to biological nature of RO7126209, changes in brain imaging results from MRIs or PET scans used during the study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with mild to moderate Alzheimer's or early-stage Alzheimer's.

Select...

I can see and hear well enough to take tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I cannot have a lumbar puncture due to health risks.

Select...

I have a diagnosed neurological condition.

Select...

My brain MRI does not show significant abnormalities.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2020 Phase 1 trial • 36 Patients • NCT04023994

75%

Back pain

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

RO7126209 (0.1 mg/kg)

RO7126209 (0.4 mg/kg)

RO7126209 (1.2 mg/kg)

RO7126209 (3.6 mg/kg)

RO7126209 (7.2 mg/kg)

Trial Design

21Treatment groups

Experimental Treatment

Placebo Group

Group I: Part 4: Open Label Extension (OLE) phase Arm 1: RO7126209Experimental Treatment1 Intervention

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.

Group II: Part 4 OLE Phase Arm 3: RO7126209Experimental Treatment1 Intervention

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.

Group III: Part 4 OLE Phase Arm 2: RO7126209Experimental Treatment1 Intervention

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.

Group IV: Part 3 Dose/Frequency/PD Relationship: Dose Level 2: RO7126209Experimental Treatment1 Intervention

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.

Group V: Part 3 (Dose/Frequency/Pharmacodynamic (PD) Relationship): Dose Level 1: RO7126209Experimental Treatment1 Intervention

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.

Group VI: Part 2 (Expansion) Cohort 3: Dose Level 3 of RO7126209Experimental Treatment1 Intervention

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.

Group VII: Part 2 (Expansion) Cohort 2: Dose Level 2 of RO7126209Experimental Treatment1 Intervention

Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group VIII: Part 2 (Expansion) Cohort 1: Dose Level 1 of RO7126209Experimental Treatment1 Intervention

Participants will receive multiple doses of RO7126209 at dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group IX: Part 1 (Dose Finding) Cohort 5: Dose Level 5 of RO7126209Experimental Treatment1 Intervention

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.

Group X: Part 1 (Dose Finding) Cohort 4: Dose Level 4 of RO7126209Experimental Treatment1 Intervention

Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XI: Part 1 (Dose Finding) Cohort 3: Dose Level 3 of RO7126209Experimental Treatment1 Intervention

Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XII: Part 1 (Dose Finding) Cohort 2: Dose Level 2 of RO7126209Experimental Treatment1 Intervention

Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XIII: Part 1 (Dose Finding) Cohort 1: Dose Level 1 of RO7126209Experimental Treatment1 Intervention

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.

Group XIV: Part 2 (Expansion) Cohort 2: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XV: Part 2 (Expansion) Cohort 3: PlaceboPlacebo Group1 Intervention

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.

Group XVI: Part 1 (Dose Finding) Cohort 5: PlaceboPlacebo Group1 Intervention

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.

Group XVII: Part 1 (Dose Finding) Cohort 1: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 1 Q4W for 28 weeks followed by a 28-week safety follow-up period.

Group XVIII: Part 1 (Dose Finding) Cohort 2: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XIX: Part 1 (Dose Finding) Cohort 3: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XX: Part 1 (Dose Finding) Cohort 4: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group XXI: Part 2 (Expansion) Cohort 1: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo to dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

RO7126209

2019

Completed Phase 1

~40

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Alzheimer's Disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and amyloid-targeting therapies. Cholinesterase inhibitors work by increasing cholinergic transmission, providing modest symptomatic relief in cognition and global functioning. Amyloid-targeting therapies, such as monoclonal antibodies (e.g., aducanumab), aim to reduce amyloid-beta plaques in the brain, which are believed to play a key role in AD pathogenesis. These treatments are significant for AD patients as they offer potential disease-modifying effects, potentially slowing disease progression and improving quality of life.

Preventive and Therapeutic Strategies in Alzheimer's Disease: Focus on Oxidative Stress, Redox Metals, and Ferroptosis.