11C-ER176 for Alzheimer's Disease

Overseen By Alireza Faridar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Antipsychotics, Antiepileptics, Corticosteroids, others

Disqualifiers: Infections, Cardiac dysfunction, Cancer, others

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

Compensation: Varies

Number of Visits: 2

Duration: 22 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dosage of Alzheimer's medications (like rivastigmine, galantamine, donepezil, memantine) for at least 4 weeks before screening and throughout the study. Other chronic medications must also be stable for at least 30 days before screening. Some medications, like certain antipsychotics and antiepileptics, are not allowed during the study.

What makes the drug 11C-ER176 unique for Alzheimer's disease?

The drug 11C-ER176 is unique because it is a radiotracer used in PET imaging to detect tau protein accumulation in the brain, which is a hallmark of Alzheimer's disease. This approach helps in diagnosing and understanding the progression of the disease, unlike traditional treatments that focus on symptom management. ^{1 2 3 4 5}

What is the purpose of this trial?

Inflammation could provide a new focus for therapeutic intervention. In this study, we will measure blood and cerebrospinal fluid (CSF) inflammation biomarkers and compare them to measurements of brain glial activation obtained by positron emission tomography (PET). In addition, we will determine the effect of low-dose interleukin-2 (IL-2) immunotherapy, given over 22 weeks, on these inflammation biomarkers.

Eligibility Criteria

This trial is for individuals with Alzheimer's Disease. It aims to explore the role of inflammation in AD by measuring biomarkers in blood and CSF, and brain glial activation via PET scans. Participants will also receive low-dose IL-2 immunotherapy over 22 weeks.

Inclusion Criteria

My INR is below 1.4 and I've been on a stable dose of my cognition medication for 4 weeks.

Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) less than or equal to two times normal

Formal education of eight or more years

Exclusion Criteria

Suspected or known allergy to any components of the study treatments

Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion

I am not taking certain medications during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-dose interleukin-2 (IL-2) immunotherapy to assess its effect on inflammation biomarkers

22 weeks

Visits every 2 or 4 weeks depending on group assignment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of brain glial activation and inflammation biomarkers

36 months

Treatment Details

Interventions

• 11C-ER176

Trial Overview The study tests how a marker called 11C-ER176 used in PET scans can show brain inflammation. Additionally, it examines the effects of a treatment with low-dose interleukin-2 on inflammation markers in patients with Alzheimer's Disease.

Participant Groups

Group I: IL-2 every 2 weeks Active Control 1 Intervention

Aldesleukin every 2 weeks

Group II: IL-2 every 4 weeks Active Control 1 Intervention

Aldesleukin every 4 weeks

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

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 study used [(11)C]BF-227 PET imaging to identify early brain changes in patients with mild cognitive impairment (MCI), revealing that abnormal BF-227 distribution in the lateral temporal cortex can predict progression to Alzheimer's disease (AD).

BF-227 uptake was strongly correlated with the density of amyloid-β plaques in the brain, indicating its potential as a reliable biomarker for identifying MCI patients at risk of converting to AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of amyloid positron emission tomography probe [C]BF-227 uptake in mild cognitive impairment and alzheimer's disease. Shao, H., Okamura, N., Sugi, K., et al.[2016]

The PET tracer 18F-PI-2620 effectively detects tau pathology in Alzheimer's disease patients, showing significantly higher binding in brain regions associated with tau deposition compared to healthy controls, indicating its potential as a diagnostic tool.

The administration of 18F-PI-2620 was found to be safe and well tolerated, with imaging results demonstrating a strong correlation between tau uptake and cognitive impairment, suggesting its utility in assessing disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. Mueller, A., Bullich, S., Barret, O., et al.[2022]

The novel compound [18F] JNJ-64326067 shows promise for detecting tau aggregates in the brain, with significant retention observed in 4 out of 5 participants with probable Alzheimer's disease, indicating its potential efficacy in identifying neurodegenerative changes.

The dosimetry results suggest that [18F] JNJ-64326067 has a low effective dose for both males and females, making it a safe option for imaging tau pathology in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. Schmidt, ME., Janssens, L., Moechars, D., et al.[2021]

In a study of 166 subjects with varying cognitive abilities, early-phase amyloid-PET scans (using 18F-florbetapir or 18F-flutemetamol) showed strong positive correlations with 18F-FDG-PET scans, indicating that they can effectively assess both amyloid deposition and neurodegeneration in Alzheimer's disease.

The early-phase amyloid-PET imaging demonstrated comparable ability to discriminate Alzheimer's patients from healthy controls, suggesting it could replace 18F-FDG-PET imaging in clinical practice, potentially reducing costs while maintaining diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-phase 18F-Florbetapir and 18F-Flutemetamol images as proxies of brain metabolism in a memory clinic setting. Boccalini, C., Peretti, DE., Ribaldi, F., et al.[2023]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of amyloid positron emission tomography probe [C]BF-227 uptake in mild cognitive impairment and alzheimer's disease. [2016]

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

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. [2021]

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

Early-phase 18F-Florbetapir and 18F-Flutemetamol images as proxies of brain metabolism in a memory clinic setting. [2023]