Clinical trial NCT05999084: Georgia Memory Net Anti-Amyloid Monoclonal Antibody Registry
Official title: Georgia Memory Net Center for Medicare and Medicaid Services Registry for Anti-Amyloid Monoclonal Antibody Coverage with Evidence Development
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer Disease
Keywords: Monoclonal antibodies
Amyloid
Mild Cognitive Impairment
Lecanemab
Leqembi
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Medicare and Medicaid Services
First posted: 2023-08-21
Enrollment: 735
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study includes patients receiving care through the Emory Cognitive Neurology Clinic and Georgia Memory Net (GMN) clinics, and their caregivers.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Quick Dementia Rating System (QDRS) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Change in Functional Activities Questionnaire (FAQ) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Change in Lawton-Brody Activities of Daily Living (ADL) Physical Self-Maintenance Scale (PSMS) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Change in Lawton-Brody Instrumental Activities of Daily Living (IADL) Scale Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
Secondary outcomes:
measure: Change in Care Needs Assessment Tool (CNAT) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Change in Zarit Burden Interview Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
measure: Change in Patient-Reported Outcomes Measurement Information System Global Health (PROMIS 10) Score
timeFrame: Baseline and every 6 months until end of study (up to 5 years)
Other outcomes:
Locations:
city: Albany
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Albany
state: Georgia
city: Atlanta
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Augusta
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Augusta
state: Georgia
city: Gainesville
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Gainesville
state: Georgia
city: Macon
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Macon
state: Georgia
city: Savannah
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Savannah
state: Georgia
city: Vidalia
country: United States
facility: Georgia Memory Net Memory Assessment Clinic - Vidalia
state: Georgia
Study officials:
affiliation: Emory University
name: James J Lah, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: