Aducanumab + Exablate BBB Disruption for Alzheimer's Disease

Overseen by Ali Rezai

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Ali Rezai

Must be taking: Monoclonal antibodies

Disqualifiers: Cardiac disease, Liver disease, Depression, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for early Alzheimer's disease and mild cognitive impairment. It combines a special drug with a technique to help the drug enter the brain more effectively. The goal is to see if this combination is safe and if it can reduce harmful brain proteins.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Aducanumab for Alzheimer's disease?

Aducanumab has been shown to reduce clinical decline in patients with mild cognitive impairment and mild Alzheimer's disease by targeting and reducing brain amyloid plaques, as demonstrated in the phase 3 clinical trial EMERGE. ^{1 2 3 4 5}

What safety data exists for Aducanumab and Exablate treatments?

Aducanumab has been associated with amyloid-related imaging abnormalities, which are significant treatment-related side effects. Its long-term safety is still being evaluated in ongoing studies. There is no specific safety data available for Exablate treatments in the provided research articles. ^{1 2 3 4 6}

What makes the drug Aducanumab + Exablate BBB Disruption unique for Alzheimer's disease?

This treatment is unique because it combines Aducanumab, a drug that targets and helps clear amyloid beta plaques in the brain, with Exablate BBB Disruption, a technique that temporarily opens the blood-brain barrier to potentially enhance drug delivery to the brain, which is not a feature of other Alzheimer's treatments. ^{2 4 5 6 7}

Research Team

Ali Rezai

Principal Investigator

WVU Rockerfeller Neuroscience Institute

Eligibility Criteria

This trial is for people with mild Alzheimer's or cognitive impairment who can communicate during the procedure, have certain scores on mental and depression scales, a specific type of PET scan result, and a reliable caregiver. It excludes those with significant heart disease, liver issues, bleeding disorders, severe depression risk of suicide, untreated sleep apnea, epilepsy, impaired kidney function or are in another clinical trial.

Inclusion Criteria

Short form Geriatric Depression Scale (GDS) score of <= 7

Amyloid PET scan consistent with the presence of β-amyloid (A+)

Able and willing to give informed consent

Exclusion Criteria

A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)

Significant depression (GDS > 7) and/or potential risk of suicide (C-SSRS > 2)

Known sensitivity/allergy to gadolinium (gadobutrol), DEFINITY or its components, or 18F-florbetaben

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks followed by blood-brain barrier opening using the Exablate Model 4000 Type 2 device

Variable, based on standard of care

Every 2-4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurological and cognitive/behavioral examinations and MRI assessments

Up to 5 years post last treatment

Treatment Details

Interventions

• Aducanumab (Monoclonal Antibodies)
• Exablate Model 4000 Type 2 (Blood-Brain Barrier Disruption)

Trial Overview The study tests the safety of combining Aduhelm (Aducanumab) infusions with Exablate Model 4000 Type 2 device to open the blood-brain barrier in patients. The goal is to see if this combination is safe and feasible for treating mild Alzheimer's disease or cognitive impairment.

Participant Groups

Group I: Infusion plus Exablate BBBO Treatment Experimental Treatment 3 Interventions

Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.

Aducanumab is already approved in Canada, Japan for the following indications:

Approved in Canada as Aducanumab for:

• Not approved due to insufficient evidence of efficacy

Approved in Japan as Aducanumab for:

• Not approved due to insufficient evidence of efficacy

Who Is Running the Clinical Trial?

Ali Rezai

Lead Sponsor

Trials

6

Recruited

90+

InSightec

Industry Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Findings from Research

Aducanumab, the first FDA-approved therapy for Alzheimer's disease, has been shown to reduce clinical decline in patients with mild cognitive impairment and mild dementia, based on data from the phase 3 EMERGE trial.

Long-term modeling predicts that aducanumab treatment can lead to significant benefits, including an increase of 0.65 quality-adjusted life-years (QALYs) per patient and a delay in the progression to more severe stages of Alzheimer's, providing both clinical and socioeconomic advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. Herring, WL., Gould, IG., Fillit, H., et al.[2022]

Aducanumab, a monoclonal antibody targeting amyloid β, was approved by the FDA in June 2021 for treating Alzheimer's disease in patients with mild cognitive impairment or mild dementia, based on clinical trials conducted in this specific population.

The long-term safety and tolerability of aducanumab are currently being assessed in a multinational phase 3b clinical study, as there is no data on its effectiveness or safety for patients at different stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab: First Approval. Dhillon, S.[2021]

In the phase 3 studies EMERGE and ENGAGE, high-dose aducanumab showed significant treatment effects in EMERGE but not in ENGAGE, with post-hoc analyses revealing that differences were influenced by a small number of rapidly progressing patients and lower exposure to the target dose in ENGAGE.

The results were consistent in later enrolled patients who received the target dose of 10 mg/kg, indicating that proper dosing and patient selection are crucial for the efficacy of aducanumab in treating early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. Mallinckrodt, C., Tian, Y., Aisen, PS., et al.[2023]

Aducanumab, a monoclonal antibody recently approved for treating mild cognitive impairment and mild Alzheimer's disease, was found to be hypothetically suitable for 57% of patients with positive cerebrospinal fluid biomarkers in a study of 70 patients.

The study emphasizes the importance of developing resources to administer Aducanumab and similar anti-amyloid therapies, especially as they may soon be licensed in the European Union.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential eligibility for Aducanumab therapy in an Irish specialist cognitive service-Utilising cerebrospinal fluid biomarkers and appropriate use criteria. Togher, Z., Dolphin, H., Russell, C., et al.[2022]

Aducanumab is a monoclonal antibody that targets aggregated amyloid β (Aβ) in Alzheimer's disease, showing an objective reduction in Aβ levels but conflicting results regarding its clinical efficacy in improving symptoms.

The most significant safety concern associated with aducanumab treatment is the occurrence of amyloid-related imaging abnormalities, which raises questions about its overall risk-benefit profile despite its recent accelerated approval by the FDA for mild Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab for the treatment of Alzheimer's disease. Tagliapietra, M.[2022]

Aducanumab, a monoclonal antibody targeting amyloid beta, was generally well tolerated at doses up to 30 mg/kg in patients with mild-to-moderate Alzheimer's disease, with no severe adverse events reported.

At the highest dose of 60 mg/kg, some patients experienced serious adverse events related to amyloid-related imaging abnormalities, but these resolved within 8 to 15 weeks, indicating a need for careful monitoring at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. Ferrero, J., Williams, L., Stella, H., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Aducanumab: First Approval. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Investigating Partially Discordant Results in Phase 3 Studies of Aducanumab. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Aducanumab Use in Symptomatic Alzheimer Disease Evidence in Focus: A Report of the AAN Guidelines Subcommittee. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Potential eligibility for Aducanumab therapy in an Irish specialist cognitive service-Utilising cerebrospinal fluid biomarkers and appropriate use criteria. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Aducanumab for the treatment of Alzheimer's disease. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. [2020]