Georgia Memory Net Anti-Amyloid Monoclonal Antibody Registry

Emory University

Status: Enrolling

Conditions: Alzheimer Disease

Treatments: Drug: Anti-amyloid Monoclonal Antibodies (mAbs); Combination Product: Standard of Care

Study type: Observational

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT05999084

STUDY00006475

Details and patient eligibility

About

The purpose of this registry is to compile information on patients who are receiving FDA-approved anti-amyloid mAbs in the course of their clinic visits in the Emory Cognitive Neurology Clinic and in Georgia Memory Net Memory Assessment Clinics.

Full description

Alzheimer's disease is a devastating neurodegenerative illness impacting millions of Americans including patients and caregivers. Treatments have been limited to symptomatic therapies leading to the pervasive sentiment that 'nothing can be done'; however, recent advances in the field have created excitement and hope for patients, families, and healthcare providers. On 6 January 2023, the anti-amyloid monoclonal antibody (mAb) lecanemab received accelerated approval from the Food and Drug Administration (FDA). A similar medication, donanemab, also recently demonstrated positive results in a large trial. Despite the positive trials, questions remain about anti-amyloid mAbs efficacy as well as how they will perform in a real-world setting. The Centers for Medicare & Medicaid Services (CMS) released a National Coverage Analysis (NCA) Memo with a framework for deploying anti-amyloid mAbs in a way that improves understanding of benefit and harm.

This registry will be managed through Georgia Memory Net (GMN), an initiative that was launched in 2018 to build statewide capacity for early and specific diagnosis of Alzheimer's disease and related dementias (ADRD), improve patient and caregiver support, and provide access to emerging disease modifying therapies. The GMN supports Memory Assessment Clinics (MACs) geographically distributed at 7 sites around the state with common data elements modeled on best practices developed in the Emory University Cognitive Neurology Memory Assessment Clinic over the past 25 years. The GMN infrastructure and care model provides an optimal real-world testing ground for evidence development on the effectiveness, safety, and appropriate use of anti-amyloid mAbs in the Medicare population.

The clinical data for patients treated with anti-amyloid mAbs will be compared to historical clinical data from comparable patients who were seen in GMN clinics prior to availability of anti-amyloid mAbs. Patients in the registry will be followed for the duration of their initial treatment as specified by FDA for specific anti-amyloid monoclonal antibody and subsequent maintenance treatment which is currently unspecified.

The objectives of this registry are to:

1. Monitor clinical use of FDA approved anti-amyloid mAbs to report health outcomes for patients in broad community practice.
2. Understand how patient characteristics, treating clinicians, and clinical settings impact benefits and harms (brain hemorrhage and edema) of FDA approved anti-amyloid mAbs.
3. Define how benefits and harms of FDA approved anti-amyloid mAbs change over time.

Enrollment: 735 estimated patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 50-90, inclusive

2. Diagnosis: Mild Cognitive Impairment (MCI) or mild AD dementia with positive cerebrospinal fluid (CSF) or amyloid PET

3. Objective measurement of baseline cognition and function within past 3 months:

   • Cognitive: Mini-Mental State Examination (MMSE) ≥ 22, MoCA ≥ 16
   • Function: Independence in basic ADLs
   • Function: FAQ ≤ 9 may justify inclusion with lower cognitive score if felt to be impacted by prominent language impairment or other factors affecting score

4. MRI brain within last year and no exclusionary criteria

5. Complete blood count (CBC), comprehensive metabolic panel (CMP), B12, thyroid stimulating hormone (TSH), prothrombin time (PT), partial thromboplastin time (PTT), and International Normalized Ratio (INR) without clinically significant abnormality

6. Informant/care partner/family available to attend follow-up visits to provide information regarding patient's cognitive and functional abilities

7. Agree to MRI, PET, and testing clinical diagnostic requirements and drug label / FDA recommendations to determine drug eligibility and appropriateness, including Apolipoprotein E (APOE) testing

Exclusion criteria

1. Any contraindication to MRI

2. MRI exclusion criteria:

   • Acute or sub-acute hemorrhage
   • Prior macro hemorrhage (>1 cm), subarachnoid hemorrhage, or known aneurysm
   • >4 microhemorrhages
   • Superficial siderosis
   • Any finding that might be a contributing cause of the subject's dementia that could pose a risk to the subject or prevent safety MRIs.

3. Seizure within the past 6 months or history of refractory epilepsy.

4. Unstable severe psychiatric illness in past 6 months

5. History of bleeding disorder, blood clotting, or clinically significant abnormal results on coagulation profile (platelet count <50,000; INR >1.5)

6. Uncontrolled diabetes (HgbA1c >9%)

7. Uncontrolled hypertension

8. History of unstable angina, myocardial infarction (MI), advanced heart failure, or clinically significant conduction abnormalities within past year.

9. End stage renal disease

10. Receiving active treatment for cancer (e.g., chemotherapy, biologics, or radiation therapy) with exceptions for maintenance therapies for cancer in remission (e.g., anti-estrogen for breast cancer)

11. Systemic illness or serious infection, e.g., pneumonia, sepsis, Coronavirus disease 2029 (COVID-19), in past 30 days

12. Immunological disease requiring immunosuppression, immunoglobulins, monoclonal antibodies, or plasmapheresis

13. Exclude if breastfeeding or if female patients of childbearing potential unable to practice highly effective contraception

14. History of severe allergic or anaphylactic reactions or hypersensitivity to inactive ingredients (arginine hydrochloride, histidine, histidine hydrochloride monohydrate, polysorbate 80)

Trial design

735 participants in 3 patient groups

Anti-amyloid Monoclonal Antibodies (mAbs)

Description:

Patients with Mild Cognitive Impairment (MCI) or mild AD dementia who are receiving treatment with anti-amyloid mAbs, per standard of care. Patients seen in the Emory and GMN MACs are evaluated with standard instruments for cognitive and functional abilities.

Treatment:

Drug: Anti-amyloid Monoclonal Antibodies (mAbs)

Historical Comparator Group

Description:

Available historical data from biomarker-confirmed patients with MCI or mild dementia due to AD who have been followed in the Emory Cognitive Neurology Clinic will serve as a comparator group. Patients seen in the Emory and GMN MACs are evaluated with standard instruments for cognitive and functional abilities.

Treatment:

Combination Product: Standard of Care

Caregivers of Patients Receiving Anti-amyloid Monoclonal Antibodies (mAbs)

Description:

Caregivers of patients with Mild Cognitive Impairment (MCI) or mild AD dementia who are receiving treatment with anti-amyloid mAbs, per standard of care. Caregivers of patients seen in the Emory and GMN MACs are evaluated with standard instruments for cognitive and functional abilities.

Treatment:

Drug: Anti-amyloid Monoclonal Antibodies (mAbs)