Tau Radioligand Imaging for Alzheimer's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Dean F Wong

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Investigational drugs

Disqualifiers: Stroke, Traumatic brain injury, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is an open label study to compare three new generation TAU radioligands, 18F-RO948 (formerly known as 18F-6958948), 18F-MK6240, and \[18F\]GTP1for imaging of taupathy and demonstrate their absence of off-target binding in patients with Alzheimer disease (AD) and older healthy controls (OC). The study will directly compare AD and OC with these three next-generation TAU radioligands and compare each of them with historical data of the current most widely used first generation radioligand, 18F-AV1451. Upto38 (30 AD (Amyloid +)and 8 OC (Amyloid -), matched for age and sex with A+ subjects) male and female subjects aged 50-100 will be enrolled in this study protocol: up to 8 for Cohort 1, up to 8 for Cohort 2, and up to 22 for Cohort 3. The study consists of three cohorts: Cohort 1: Up to8 AD subjects (A+; CDR 0.5 and 1)will receive two PET scans in random order, with receiving either18F-RO948 or18F-MK6240 at the first scan. A third scan with 18F-GTP1is possible, depending on timing and radiotracer availability Cohort 2:Up to8 OC (A-; CDR=0)subjects will receive two PET scans in random order, with receiving either18F-RO948or 18F-MK6240 at the first scan. A third scan with 18F-GTP1is possible, depending on timing and radiotracer availability Cohort 3:Up to 22 (A+; CDR = 0, .5 and 1) subjects will receive three PET scans in random order, with receiving 18F-RO94818F-MK6240 or18F-GTP1at the first scan. Efforts will be made to include about 1/3 CDR = 0, 1/3 CDR .5, and 1/3 CDR 1 in Cohort 3.

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.

What data supports the effectiveness of the drug 18F-GTP1 and similar radioligands for imaging tau in Alzheimer's disease?

Research shows that radioligands like 18F-MK6240 and 18F-RO-948 are effective in identifying tau deposits in the brain, which are linked to Alzheimer's disease. These radioligands have been shown to accurately differentiate between Alzheimer's patients and healthy individuals, suggesting their potential usefulness in diagnosing and studying the disease. ^{1 2 3 4 5}

Is the tau radioligand imaging treatment safe for humans?

The tau radioligand imaging treatment, including variants like [18F]MK6240 and 18F-RO-948, has undergone preclinical safety evaluations and initial human studies, which suggest it is generally safe for use in brain imaging. These studies have shown good brain entry, rapid washout, and favorable metabolism patterns, indicating a promising safety profile. ^{1 2 3 6 7}

How does the tau radioligand imaging treatment differ from other Alzheimer's treatments?

Tau radioligand imaging is unique because it uses PET scans to visualize tau protein build-up in the brain, which is a hallmark of Alzheimer's disease. Unlike other treatments that may focus on symptoms or amyloid plaques, this approach helps in early and accurate diagnosis by specifically targeting tau aggregates, potentially improving patient outcomes. ^{1 2 3 5 8}

Research Team

Dean F Wong

Principal Investigator

Head Researcher/Professor of Radiology

Eligibility Criteria

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 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 have not completed 2 COVID-19 vaccine shots.

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

Trial Timeline

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

Treatment Details

Interventions

• 18F-GTP1 (Radiopharmaceutical)
• 18F-MK6240 (Radiopharmaceutical)
• [18F]RO-948 (Radiopharmaceutical)

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.

Participant Groups

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University School of Medicine Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2027

Patients Recruited

2,353,000+

Roche Pharma AG

Industry Sponsor

Trials

413

Patients Recruited

430,000+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

References

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

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. [2023]

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

Evaluation of 18F-RO-948 PET for Quantitative Assessment of Tau Accumulation in the Human Brain. [2019]

3. United States 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. [2022]

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

An updated radiosynthesis of [18F]AV1451 for tau PET imaging. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

PET Radioligands for Imaging of Tau Pathology: Current Status. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Characterization of MK6240, a tau PET tracer, in autopsy brain tissue from Alzheimer's disease cases. [2021]

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

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]

8. United States 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. [2019]