Anti-amyloid Immunotherapies for Alzheimer's Disease

Overseen By Casey McAdam

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Anti-amyloid immunotherapies

Disqualifiers: Pregnancy, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

135 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an imaging study of patients with mild Alzheimer's disease receiving amyloid-targeting therapy and under the care of neurologists at Mayo Clinic in Rochester, MN.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug 18F-flortaucipir for Alzheimer's disease?

Research shows that 18F-flortaucipir PET scans can help track the progression of Alzheimer's disease by measuring tau protein buildup in the brain, which is linked to cognitive decline. This drug has been approved by the FDA for its ability to provide valuable information about the near-term clinical progression of Alzheimer's disease. ^{1 2 3 4 5}

Is 18F-flortaucipir safe for humans?

The studies involving 18F-flortaucipir, used in PET imaging for Alzheimer's disease, do not report specific safety concerns, suggesting it is generally safe for human use in the context of these trials. ^{1 2 4 5 6}

What makes the drug 18F-flortaucipir unique for Alzheimer's disease?

18F-flortaucipir is unique because it is a PET imaging tracer that specifically binds to tau protein tangles in the brain, which are a hallmark of Alzheimer's disease. This allows for the visualization and measurement of tau distribution and density, aiding in the diagnosis and understanding of the disease's progression. ^{3 4 6 7 8}

Research Team

Petrice Cogswell, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for people aged 50-90 with mild cognitive impairment or early Alzheimer's, confirmed by amyloid presence. They must be able to consent and fit the criteria for anti-amyloid therapy. It excludes claustrophobic individuals, those with heart rhythm issues (prolonged QT interval), anyone unable to stay still for scans, and pregnant or breastfeeding women.

Inclusion Criteria

Amyloid positive via CSF or PET

Meets other eligibility criteria for anti-amyloid immunotherapy

I have mild memory loss or mild Alzheimer's disease.

Exclusion Criteria

I cannot stay still lying down for 10 minutes.

I am not pregnant and can stop breastfeeding for 24 hours.

Claustrophobic patients unable to tolerate the scans (no sedation can be offered)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-amyloid immunotherapy and undergo tau PET scans

18 months

Regular visits for treatment and PET scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 18F-flortaucipir

Trial Overview The study tests how tau PET imaging changes in patients taking anti-amyloid immunotherapies. Tau PET uses a tracer called 18F-flortaucipir to visualize brain changes associated with Alzheimer's disease.

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

Subjects with a diagnosis of mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease and amyloid positive, who are starting anti-amyloid immunotherapy.

Group II: Control Group Active Control 1 Intervention

Untreated historical controls enrolled in Mayo Clinic Study of Aging (IRB 14-004401), Mayo Alzheimer's Disease Research Center (IRB 712-98), and Brain Amyloid Imaging with Pittsburgh Compound B in Normal Aging, Mild Cognitive Impairment, and Dementia (IRB 08-005553).

18F-flortaucipir is already approved in United States, European Union for the following indications:

Approved in United States as Tauvid for:

• Diagnosis of Alzheimer's disease

Approved in European Union as Tauvid for:

• Diagnosis of Alzheimer's disease

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

This study found a strong correlation (Pearson r = 0.81) between flortaucipir PET imaging results and levels of abnormally phosphorylated tau (Ptau) in brain tissue from patients with dementia, suggesting that flortaucipir can effectively reflect tau pathology in Alzheimer's disease.

The research indicates that while flortaucipir PET correlates well with Ptau levels, it does not show a significant relationship with amyloid-β (Aβ1-42), highlighting its potential specificity for tau-related changes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. Pontecorvo, MJ., Keene, CD., Beach, TG., et al.[2021]

The FDA-approved radiotracer 18F-flortaucipir is increasingly used in PET imaging to visualize tau pathology in patients with cognitive impairment, particularly Alzheimer's disease.

An international consensus has been established to standardize the procedural use of 18F-flortaucipir PET imaging, which will enhance its application in clinical practice for diagnosing and managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. Tian, M., Civelek, AC., Carrio, I., et al.[2022]

In a study of 45 patients with various frontotemporal dementia (FTD) syndromes, 18F-flortaucipir PET imaging showed some elevated tau binding in specific brain regions, particularly in patients with nonfluent variant primary progressive aphasia (nfvPPA) and corticobasal syndrome (CBS).

However, the overall sensitivity and specificity of 18F-flortaucipir for detecting tau aggregates in FTD were limited, indicating a need for further research and the development of more specific imaging agents for FTD-related tau pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Tsai, RM., Bejanin, A., Lesman-Segev, O., et al.[2021]

In a study involving 202 participants aged 50 and older, flortaucipir PET imaging revealed a significant increase in tau burden over 18 months in individuals with amyloid-β, indicating a relationship between tau accumulation and cognitive decline in Alzheimer's disease.

The study found that both the initial tau levels and the changes in tau burden were strongly associated with cognitive performance, suggesting that monitoring tau levels could help predict cognitive deterioration in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. Pontecorvo, MJ., Devous, MD., Kennedy, I., et al.[2022]

Flortaucipir PET scans can effectively predict near-term clinical progression in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), with 70% of those showing an advanced AD pattern experiencing significant clinical deterioration over 18 months.

The study involved 364 participants, and those with an advanced AD pattern had a higher risk of clinical decline compared to those with a nonadvanced pattern, indicating that these scans can provide valuable prognostic information for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. Lu, M., Pontecorvo, MJ., Devous, MD., et al.[2022]

In a study involving 33 patients with progressive supranuclear palsy (PSP), 18 F-flortaucipir showed significantly elevated uptake in specific brain regions compared to normal controls (46 participants) and patients with Parkinson disease (26 participants), indicating its potential as a biomarker for tau pathology in PSP.

The globus pallidus region was particularly effective in distinguishing PSP patients from both controls and Parkinson disease patients, with high accuracy (AUC values of 0.872 and 0.893, respectively), suggesting that 18 F-flortaucipir could aid in the diagnosis of PSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. Schonhaut, DR., McMillan, CT., Spina, S., et al.[2022]

18F-Florbetapir PET imaging is effective for detecting β-amyloid plaques, while 18F-Flortaucipir PET is useful for visualizing tau protein tangles, both of which are critical for diagnosing Alzheimer's disease (AD).

Combining data from both amyloid and tau PET scans can enhance the accuracy of differential diagnosis and prognosis in patients with mild cognitive impairment or suspected AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series. James, OG., Linares, AR., Hellegers, C., et al.[2023]

In a study involving 25 participants (18 with Alzheimer's disease, 3 with mild cognitive impairment, and 4 healthy controls), the novel tau PET tracer [18F]RO948 demonstrated higher retention in the entorhinal cortex and lower off-target binding in other brain regions compared to [18F]flortaucipir.

Both tracers showed comparable binding in neocortical regions, but [18F]RO948's reduced off-target binding and stable retention over time suggest it may provide more accurate diagnostic information for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948. Smith, R., Schöll, M., Leuzy, A., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. [2022]

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

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. [2022]

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

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. [2022]

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

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948. [2021]