Tau Radioligand Imaging for Alzheimer's Disease

Recruiting at 1 trial location

Overseen By Catie Fisher, BS, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Investigational drugs

Disqualifiers: Stroke, Traumatic brain injury, HIV, others

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

Compensation: Varies

Number of Visits: 3

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore new imaging techniques to better understand Alzheimer's disease by testing three experimental drugs—18F-GTP1, 18F-MK6240, and [18F]RO-948—that help create clearer brain scans. Researchers will compare these drugs to current imaging methods to determine if they provide better images of tau protein build-up, a key feature of Alzheimer's. Suitable candidates for this trial include those diagnosed with probable Alzheimer's disease, who have stable medication use, and can tolerate PET scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new imaging drugs.

Do I need to stop my current medications for the trial?

The trial requires that any medications you are taking should be stable for at least 4 weeks before starting the study, and you should not expect to change the use or dose during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the tau radioligands—18F-GTP1, 18F-MK6240, and 18F-RO948—are generally safe for humans.

18F-GTP1 has been used in studies with both Alzheimer's patients and healthy individuals. Although detailed safety information remains limited, these studies suggest it is safe for imaging.

18F-MK6240 has not presented any safety issues in people. It was well tolerated, meaning it did not cause major side effects during brain scans.

18F-RO948 is known for its ability to specifically target Alzheimer's disease tau. While detailed safety data is limited, previous studies suggest it is safe for diagnostic imaging.

Overall, these radioligands are in early trials, so researchers continue to closely monitor safety. However, based on current studies, they appear well-tolerated in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these tau radioligand imaging agents—18F-GTP1, 18F-MK6240, and [18F]RO-948—because they offer a novel way to visualize tau protein accumulation in the brain, a hallmark of Alzheimer's disease. Unlike current treatments that generally focus on managing symptoms with medications like cholinesterase inhibitors and memantine, these imaging agents help in early detection by directly targeting tau proteins. This method could potentially lead to earlier and more precise interventions, allowing for a better understanding of disease progression and the effectiveness of future therapies.

What evidence suggests that this trial's radioligands could be effective for imaging taupathy in Alzheimer's disease?

Research has shown that certain imaging tools, called tau PET tracers, hold promise for studying Alzheimer's disease. In this trial, participants will receive different tracers, including 18F-GTP1, 18F-MK6240, and 18F-RO948, to highlight areas in the brain where tau protein accumulates, a common feature of Alzheimer's. For instance, 18F-GTP1 can pinpoint tau accumulation in the brain. 18F-MK6240 tracks tau buildup over time, even in the disease's early stages. 18F-RO948 excels at distinguishing Alzheimer's from other brain disorders by specifically targeting tau proteins. Researchers aim to determine if these tracers can improve diagnosis and monitor Alzheimer's progression. ^{2 3 4 5 6}

Who Is on the Research Team?

Dean F Wong

Principal Investigator

Head Researcher/Professor of Radiology

Are You a Good Fit for This Trial?

This trial is for men and women aged 50-100 with probable Alzheimer's Disease (AD) who can undergo PET scans. AD participants must have a positive amyloid test, while older controls need normal cognitive function. Women of childbearing age must use contraception, and all subjects should be able to consent or have a representative do so.

Inclusion Criteria

I am between 50 and 100 years old.

Subjects who in the opinion of the investigator based on medical history and physical exam can tolerate the PET scan procedures, and can safely tolerate tracer administration and the scanning procedures

My current medications and their doses have been stable for at least 4 weeks.

Exclusion Criteria

I have not completed 2 COVID-19 vaccine shots.

I haven't lost or donated more than 450 mL of blood in the last 4 months, nor have I donated plasma in the last 14 days. I also don't have a bleeding disorder or take blood thinners.

I do not have a history of drug or alcohol abuse, or I am on prescribed narcotics with a positive drug screen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive PET scans with 18F-RO948, 18F-MK6240, and 18F-GTP1 to compare imaging capabilities

37-44 days

Up to 3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-GTP1
• 18F-MK6240
• [18F]RO-948

Trial Overview

The study tests three new TAU radioligands (18F-MK6240, [18F]RO-948, 18F-GTP1) against the first-generation radioligand in imaging tauopathy in AD patients and healthy controls. Participants will receive up to three PET scans with these tracers to compare their effectiveness.

How Is the Trial Designed?

Group I: Cohort 3: (A+; CDR = 0, .5, 1; AD) Experimental Treatment 3 Interventions

Unblinded and randomized to receive 18F-RO948or 18F-MK6240 or \[18F\]GTP1for PET Scan #1. PET scan #2 will be 18F-RO948or 18F-MK6240 or \[18F\]GTP1NOT received in PET scan #1. PET scan # 3 will be 18F-RO948or 18F-MK6240 or \[18F\]GTP1NOT received in PET scan #1 or #2. Efforts will be made to include about 1/3 CDR = 0; 1/3 CDR = .5; 1/3 CDR = 1 in Cohort 3. Efforts will also be made to completethe study with about equal numbers of subjects whose PET scan #1 start with each of the three tracers.

Group II: Cohort 2: (A-; CDR=0; OC) Experimental Treatment 3 Interventions

Unblinded and randomized to receive either 18F-RO948or 18F-MK6240 for PET Scan #1. PET scan #2 will be either 18F-RO948or 18F-MK6240 NOT received in PET scan#1.If a 3rdPET scan occurs, this third scan will always be \[18F\]GTP1.

Group III: Cohort 1: (A+; CDR = .5, 1; AD) Experimental Treatment 3 Interventions

Unblinded and randomized to receive either 18F-RO948or 18F-MK6240 for PET Scan #1. PET scan #2 will be either 18F-RO948or 18F-MK6240 NOT received in PET scan #1. If a 3rdPET scanoccurs,this third scanwill always be \[18F\]GTP1.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Published Research Related to This Trial

The rising incidence of Alzheimer's disease (AD) among the elderly highlights the urgent need for early and accurate diagnosis, as current disease-modifying drugs are still in clinical trials and are expected to be most effective in the early stages of the disease.

This review emphasizes the importance of developing tau-specific positron emission tomography (PET) radioligands, which could significantly aid in the early detection and diagnosis of AD, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Radioligands for Imaging of Tau Pathology: Current Status. Choe, YS., Lee, KH.[2020]

3H-MK6240, a second-generation tau PET tracer, shows high binding affinity for neurofibrillary tangles in Alzheimer's disease (AD) brain tissue, with significantly higher binding observed in AD patients compared to controls.

The study found that 3H-MK6240 has distinct binding characteristics compared to first-generation tau tracers, indicating its potential for more accurate detection of tau deposits in AD, particularly in early-onset cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of MK6240, a tau PET tracer, in autopsy brain tissue from Alzheimer's disease cases. Malarte, ML., Nordberg, A., Lemoine, L.[2021]

The novel PET tracer 18F-RO-948 shows superior binding characteristics for detecting tau pathology in Alzheimer's disease compared to other tracers 11C-RO-963 and 11C-RO-643, based on human evaluations involving amyloid PET-positive AD subjects and healthy controls.

In the study, 18F-RO-948 effectively discriminated between Alzheimer's patients and healthy individuals, revealing significant differences in tau accumulation across multiple brain regions, indicating its potential as a valuable tool for diagnosing and understanding Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects. Wong, DF., Comley, RA., Kuwabara, H., et al.[2019]

The PET imaging agent [18F]MK6240 effectively detects tau aggregates in the brain, showing a wide dynamic range of uptake in subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), which aligns with known patterns of tau deposition.

While various quantification methods for [18F]MK6240 were tested, including compartmental and reference tissue models, caution is advised in using simplified methods for high binding cases due to potential underestimation of tau levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. Guehl, NJ., Wooten, DW., Yokell, DL., et al.[2023]

The modified synthesis of [18F]AV1451 allows for the production of high-yield doses (202 ± 57 mCi) with excellent radiochemical purity (98 ± 1%), making it suitable for clinical imaging of tau deposits in Alzheimer's disease.

This new method simplifies the production process by using only 0.5 mg of precursor and automating the synthesis, which enhances efficiency and accessibility for clinical tau PET studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated radiosynthesis of [18F]AV1451 for tau PET imaging. Mossine, AV., Brooks, AF., Henderson, BD., et al.[2022]

The novel radioligand 18F-RO-948 effectively identifies tau positivity in patients with mild Alzheimer's disease, demonstrating its potential for quantitative imaging of tau in the brain.

In a study involving 11 Alzheimer's patients and 10 control subjects, 18F-RO-948 showed excellent reproducibility and successfully distinguished Alzheimer's patients from older and younger controls, particularly in specific brain regions associated with tau accumulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 18F-RO-948 PET for Quantitative Assessment of Tau Accumulation in the Human Brain. Kuwabara, H., Comley, RA., Borroni, E., et al.[2019]

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

Three novel compounds (RO6958948, RO6931643, and RO6924963) have been identified as high-affinity binders to tau aggregates in Alzheimer's disease, showing potential as PET tracers for imaging these aggregates in the brain.

In vivo studies in tau-naïve baboons demonstrated that these compounds have good brain uptake and favorable metabolism, indicating their suitability for future use in human imaging studies of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease. Honer, M., Gobbi, L., Knust, H., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34852837/

Baseline [ 18 F]GTP1 tau PET imaging is associated with ...

Our results suggest that [ 18 F]GTP1 tau PET represents a prognostic biomarker in AD and are consistent with data from other tau PET tracers.

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0197458019301824

Cross-sectional associations between [18F]GTP1 tau PET ...

[18F]GTP1 selectively binds to tau pathology in AD. It demonstrates significant uptake (suggesting substantial tau deposition) in AD subjects but no uptake in ...

3.

alz-journals.onlinelibrary.wiley.com

alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.055090

A comparison of longitudinal [18F]GTP1 tau pet with other ...

We sought to assess the longitudinal performance of tau PET imaging and to determine the relationships between the multiple imaging and ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02640092

Longitudinal Evaluation of [18F]GTP1 as a PET ...

The overall goal of this protocol is to evaluate the longitudinal change in tau burden using [18F]GTP1, a tau targeted radiopharmaceutical. Official Title.

5.

frontiersin.org

frontiersin.org/journals/neuroimaging/articles/10.3389/fnimg.2024.1355402/full

Evaluation of partial volume correction and analysis ...

We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [ 18 F]GTP1 tau positron-emission ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8569333/

Tau-PET imaging as a molecular modality for Alzheimer's ...

Considering the evolving literature in AD and PET imaging, it has become clear that PET can play a role in the diagnosis and prognosis of AD.