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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of 18F-flortaucipir, an anti-amyloid immunotherapy, for individuals with mild Alzheimer's disease. The goal is to determine if this treatment can help by targeting amyloid, a protein linked to Alzheimer's, in the brain. Participants will either receive the treatment or be compared to historical data from individuals with Alzheimer's who did not receive the treatment. Suitable candidates have mild memory issues due to Alzheimer's and confirmed amyloid build-up through tests like PET scans. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that 18F-flortaucipir is likely to be safe for humans?

Research has shown that 18F-flortaucipir is approved by the FDA for brain scans, aiding doctors in checking for Alzheimer's disease. This approval confirms its safety in these scans. Reports indicate it is generally well-tolerated, with most people not experiencing serious side effects. However, as with any medical treatment, some risks exist. Common issues may include headaches or reactions at the injection site. Always discuss any concerns with your doctor to understand how this treatment might affect you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about 18F-flortaucipir because it offers a unique approach to tackling Alzheimer's disease. Unlike standard treatments which often focus on managing symptoms, 18F-flortaucipir is designed to target and visualize tau protein tangles in the brain, a hallmark of Alzheimer's disease progression. This imaging agent allows for a more precise understanding of disease progression, potentially leading to more tailored and effective treatment strategies. By providing a clearer picture of what's happening inside the brain, it could revolutionize how we diagnose and monitor Alzheimer's disease, paving the way for more targeted interventions.

What evidence suggests that 18F-flortaucipir might be an effective treatment for Alzheimer's?

Research has shown that 18F-flortaucipir effectively identifies tau proteins, which are linked to Alzheimer's disease. In studies, PET scans using 18F-flortaucipir have demonstrated that tau buildup patterns align more closely with Alzheimer's severity than amyloid plaques alone. This could help identify disease progression. Early results suggest this method provides a clearer view of the brain's condition, potentially improving Alzheimer's monitoring. While it doesn't treat Alzheimer's, it helps doctors understand brain changes, crucial for managing the disease. Participants in this trial will join either a treatment group receiving anti-amyloid immunotherapy or a control group of untreated historical controls. ^{6 7 8 9 10}

Who Is on the Research Team?

Petrice Cogswell, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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 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]

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]

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]

Citations

1. nature.com nature.com/articles/s41598-023-35389-w

Deep learning application for the classification of ... - Nature This study aimed to evaluate the utility of 18 F-flortaucipir-PET images and multimodal data integration in the differentiation of CU from MCI or AD through DL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11960607/

Development and Validation of a 18F-Flortaucipir PET ... A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. Brain ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02016560?term=AV-1451-A05%20&rank=3

Analysis of 18F-AV-1451 PET Imaging in Cognitively ... To accomplish this goal, the protocol investigated flortaucipir results in younger and older cognitively healthy normal volunteers and patients with clinical ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251403

Integrating 18F-flortaucipir (TAUVID) PET/CT/MRI into Clinical ... NFT deposition patterns correlate more closely with cognitive decline and AD severity compared to amyloid plaque presence and decreased brain ...

5. academic.oup.com academic.oup.com/brain/article/142/6/1723/5476105

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

6. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/tauvid

Tauvid | European Medicines Agency (EMA) Tauvid is a diagnostic medicine that is used during brain scans in adults with cognitive impairment (memory and thinking problems) who are being evaluated for ...

7. pi.lilly.com pi.lilly.com/us/tauvid-uspi.pdf

tauvid-uspi.pdf The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. Preliminary non- clinical and clinical investigations ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/212123s000lbl.pdf

1 This label may not be the latest approved by FDA. For ... TAUVID contains flortaucipir fluorine 18 (F 18). Chemically, flortaucipir F ... dementia, 1 had mild cognitive impairment, and 14 had no cognitive impairment on ...

9. go.drugbank.com go.drugbank.com/drugs/DB14914

Flortaucipir F-18: Uses, Interactions, Mechanism of Action It is used as a marker in positron emission tomography (PET) imaging of patients suspected of having Alzheimer's disease. After crossing the blood-brain barrier ...

10. jnm.snmjournals.org jnm.snmjournals.org/content/61/10/1411

Brain Tau Imaging: Food and Drug Administration Approval of ... The FDA approved 18 F-flortaucipir, a new PET molecular entity designed to estimate the density and distribution of the aggregated intracellular NFTs.