NCT07633470 - A Study of Zunveyl on Safety, Tolerability, Neuropsychiatric Symptoms, and Caregiver Distress in Alzheimer's Disease (RESOLVE) | Crick | Crick
A Study of Zunveyl on Safety, Tolerability, Neuropsychiatric Symptoms, and Caregiver Distress in Alzheimer's Disease (RESOLVE)
The primary purpose of this study is to evaluate the safety and tolerability of Zunveyl® over 12 weeks of routine clinical use in adults with mild to moderate Alzheimer's disease.
Inclusion Criteria:
1. Male and female outpatients aged 50 years and greater at the time of informed consent.
2. Diagnosis of probable Alzheimer's disease in accordance with the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, supported by biomarker confirmation using the Fujirebio Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio test.
3. Cognitive impairment consistent with mild-to-moderate Alzheimer's disease, confirmed at Screening by the Saint Louis University Mental Status (SLUMS) examination, with scores meeting the following criteria based on education level:
1. Less than high school education: SLUMS score 10 -18
2. High school education or higher: SLUMS score 10 - 20
4. The participant must be capable of providing informed consent; if not, a legally authorized representative (LAR)/caregiver may provide consent in compliance with federal and Institutional Review Board (IRB) regulations.
5. Participant currently receiving non-exclusionary chronic medications are eligible, provided doses have been stable for greater than or equal to \[\>=\] 4 weeks.
6. Any recent medication changes at baseline (less than 8 weeks) should be reviewed to confirm they are not expected to confound efficacy or safety assessments.
7. Availability of a reliable full-time caregiver or study partner who serves as a knowledgeable informant and:
1. Has at least 20 hours per week of direct contact with the participant;
2. Is capable of consistently completing tolerability assessments and the Neuropsychiatric Inventory (NPI) across study visits;
3. Can observe and accurately report tolerability, neuropsychiatric symptoms (including sleep), and caregiver distress;
4. Is available and willing to participate in all required study visits and assessments.
8. Participants must not have received disallowed concomitant medications within 2 weeks or 5 half-lives (whichever is longer) prior to baseline.
9. Compliance with washouts will be confirmed by medication history review.
10. The participant and caregiver must be willing and able to comply with all study procedures, including visits, assessments, and follow-up in an outpatient setting.
Exclusion Criteria:
1. Dementia due to causes other than Alzheimer's disease, including but not limited to vascular dementia, frontotemporal dementia, or substance/medication-induced dementia, Parkinson's disease dementia and Lewy body dementia, Huntington's dementia, or any other types.
2. Negative biomarkers result on the Fujirebio Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio test, indicating lack of biomarker support for a diagnosis of probable Alzheimer's disease according to the 2024 NIA-AA criteria.
3. Hospitalization in a psychiatric or mental health facility (For example \[e.g.\], psychiatric hospital, inpatient ward) at screening or within 3 months prior to screening.
4. Any concurrent or unstable medical condition that, in the investigator's judgment, could interfere with study conduct, confound interpretation of study data, or pose an undue risk to the participant's safety. Includes but is not limited to:
1. Malignancy within the past 2 years, except for adequately treated non-melanotic skin cancer, localized prostate cancer or cervical cancer in situ (other non-metastatic malignancies may be allowed with medical monitor approval).
2. Hematologic, endocrine, metabolic, cardiovascular, pulmonary, renal, hepatic, gastrointestinal, or neurologic disorders that are unstable or progressive.
3. Cardiovascular examples: three documented episodes of blood pressure greater than (\>)185/100 millimeters of mercury (mmHg), unstable ischemic heart disease, dilated cardiomyopathy, unstable valvular disease, cardiac conduction abnormalities, or bradycardia (participants will be excluded if resting (awake) heart rate (HR) less than (\<) 50 beats per minute (bpm) confirmed on repeat, or any symptomatic bradycardia.
5. Current active clinical diagnosis of delirium, psychosis or psychotic disorder, per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
6. Active major depression requiring initiation or recent change of antidepressant therapy within 2 months prior to Screening.
7. Active symptoms of diarrhea, nausea, vomiting, or abdominal pain/discomfort or any Gastrointestinal (GI) condition that may impact IP absorption, e.g. gastric bypass surgery during screening or scheduled or prn medications to treat these conditions (e.g., loperamide, ondansetron, antispasmodic drugs).
8. History of seizure disorder, anorexia nervosa, or bulimia.
9. Acute delirium at baseline (e.g., positive Confusion Assessment Method \[CAM\]) that has not been resolved prior to enrollment.
10. Known hypersensitivity or contraindication to Zunveyl® or galantamine-containing products.
11. Use of an investigational drug or device for neuropsychiatric symptoms within 30 days or 5 half-lives, whichever is longer prior to Baseline.
12. Life expectancy \<12 months, or a hospice/palliative plan of care inconsistent with study participation.
13. Any medical, neurological, or psychiatric condition that, in the investigator's judgment, may place the participant at risk, interfere with assessments, or compromise study participation.
14. Any participant currently receiving or who has ever received Zunveyl®.
15. Weight loss of \>10 in the 6-month period prior to screening.
16. Any planned general surgery during the duration of the study.
17. History of Stevens-Johnson Syndrome (TENS).
18. Significantly abnormal labs including Estimated Glomerular Filtration Rate (eGFR) \<10 or Liver function Tests (LFTs) \>2\*Upper Limit of Normal (ULN).
19. Concomitant medications that cannot be stopped including strong Cytochrome P450 (CYP) inhibitors/inducers of 3A4 or 2D6 or a high anticholinergic burden defined as an Anticholinergic Cognitive Burden (ACB) score \> 3 within 28 days prior to baseline. Any new neuropsychiatric medication that would need to be initiated during the study.
Locations (1)
Tekton Research Saint Louis Psychiatry
St Louis, Missouri, United States
RECRUITING
Outcomes
Primary Outcomes
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Week 1 up to Week 12
Percentage of Participants who Discontinued due to AEs
Time frame: From Week 1 up to Week 12
Number of Participants with Treatment Interruptions or Dose Reductions
Time frame: From Week 1 up to Week 12
Global Tolerability Score
Functional Assessment of Chronic Illness Therapy (FACIT) General Physical Well-Being domain Item 5 (GP5) will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much). Higher scores indicate greater bother from treatment side effects and worse treatment toxicity.
Time frame: At Weeks 1, 2, 4, 6, 8 12, and 17
Secondary Outcomes
Change from Baseline in Neuropsychiatric Symptoms as Measured by Neuropsychiatric Inventory - 12 Domain (NPI-12) Total Score up to Week 12
The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. NPI: Total score ranges from 0 to 144, with higher scores indicating worse neuropsychiatric symptoms. Each domain is scored as frequency × severity (0-12 per domain). Assesses 12 domains including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep and night-time behavior disorders, and appetite/eating abnormalities.
Time frame: Baseline up to Week 12
Change from Baseline in Total Caregiver Distress Score up to Week 12
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The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. NPI: Total score ranges from 0 to 144, with higher scores indicating worse neuropsychiatric symptoms. Each domain is scored as frequency × severity (0-12 per domain). Assesses 12 domains including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep and night-time behavior disorders, and appetite/eating abnormalities.