Study of Daratumumab in Patients With Mild to Moderate Alzheimer's Disease (DARZAD)

  • STATUS
    Recruiting
  • End date
    Jun 1, 2023
  • participants needed
    15
  • sponsor
    Marc L Gordon, MD
Updated on 17 February 2022
positron emission tomography
dementia
mini-mental state examination
alzheimer's disease
amyloid
amyloidosis
mental state examination
memantine
donepezil
cholinesterase inhibitors
rivastigmine
galantamine
cholinesterase
vitamin b12

Summary

This is an open-label, pilot study designed to explore whether daratumumab may have a clinically meaningful effect in patients with mild to moderate Alzheimer's disease.

Description

Daratumumab is a human antibody that targets CD38. It is FDA-approved for the treatment of multiple myeloma, has broad-ranging immunomodulatory effects on nonplasma cells that express CD38, and is able to cross the blood-brain barrier. CD38 expression on CD8+ T-cells is significantly increased in the blood of early AD patients as compared with age-matched controls, and activated T-cells are capable of trafficking into the central nervous system and exerting toxic effects. This study is designed to explore whether treatment with Daratumumab may have a clinically meaningful effect on patients with mild to moderate Alzheimer's disease.

Details
Condition Alzheimer Disease
Treatment Daratumumab Injection
Clinical Study IdentifierNCT04070378
SponsorMarc L Gordon, MD
Last Modified on17 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Each subject must be 55 to 85 years of age at the screening visit
Each subject must have a diagnosis of probable AD dementia according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
Each subject must have a Mini-Mental State Examination (MMSE) score 15 and 26 at the screening visit
Each subject must have a Magnetic Resonance Imaging (MRI) scan performed during the screening period that is consistent with a diagnosis of AD
Each subject must have a positive amyloid Positron Emission Tomography (PET) scan, either performed during the screening period, or previously performed provided that the scan and result are considered acceptable by the investigator
If the subject is receiving a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine) and/or memantine, the dose must have been stable for at least 12 weeks before the screening visit, and the subject must be willing to remain on the same dose for the duration of the trial
Each subject must have a study partner who is reliable and competent. The study partner must have a close relationship with the subject, have face to face contact at least 3 days/week for a minimum of 6 waking hours/week, and be willing to accompany the subject to all required study visits
Each subject must have no clinically significant abnormal laboratory test results [complete blood count (CBC), prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), comprehensive metabolic panel (CMP), thyroid stimulating hormone (TSH), and vitamin B12 level] at the screening visit
Each subject must have results of a physical and neurological examination and vital signs within normal limits or clinically acceptable to the investigator at the screening visit
If female, the subject must be postmenopausal defined as: No menses for 12 or more months without an alternative medical cause OR permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)

Exclusion Criteria

The subject has a Rosen-modified Hachinski Ischemia Score > 4 at the screening visit
The subject has a known history of stroke or evidence from screening MRI that is clinically significant in the investigator's opinion
The subject has evidence of a clinically relevant neurological disorder other than probable AD at the screening visit, including: vascular dementia, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, mental retardation, hypoxic cerebral damage, or head trauma with loss of consciousness that led to persistent cognitive deficits
The subject has evidence of a clinically relevant or unstable psychiatric disorder, based on DSM-5 criteria, including schizophrenia or other psychotic disorder, bipolar disorder, delirium, or major depression. (Major depression in remission is not exclusionary.) A score on the 15-item Geriatric Depression Scale (GDS) of 5 or more requires an assessment by an appropriate health care professional to evaluate for the presence of major depression. Subjects with a score of 5 or more who are not diagnosed with major depression following such an assessment may be included in the trial
The subject has a history of alcoholism or drug dependency/abuse within the last 5 years before screening
The subject has been treated with any investigational product within 60 days or 5 half-lives (whichever is longer) prior to the screening visit
The subject has been treated with anti-amyloid-beta or anti-tau protein monoclonal antibodies within one year prior to the screening visit
The subject has been treated with an active vaccine targeting amyloid-beta or tau protein
The subject has received a live/live-attenuated bacterial or viral vaccine within 3 months prior to the screening visit
The subject has been treated with immunosuppressive medications, such as azathioprine, cyclosporine, methotrexate, tacrolimus, or mycophenylate, within 2 months prior to the screening visit
The subject has been treated with a course of corticosteroids longer than 5 days within 2 months prior to the screening visit
The subject is taking or is anticipated to require treatment with estrogens
The subject is taking or is anticipated to require treatment with an anticoagulant medication, including warfarin, dabigatran, rivaroxaban, apixaban, edoxaban, heparin, or enoxaparin
The subject is taking or is anticipated to require treatment with aspirin at a dose higher than 325 mg daily
The subject has a history of asthma or chronic obstructive pulmonary disease
The subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions (e.g., coronary artery bypass graft, percutaneous coronary intervention via cardiac catheterization, thrombolytic therapy) within 6 months prior to the screening visit
The subject has had an infection requiring medical intervention within 30 days prior to the screening visit
The subject has serologic evidence of current or prior hepatitis B virus (HBV) infection based on hepatitis B surface antigen or hepatitis core antibody blood tests at the screening visit
The subject has serologic evidence of hepatitis C virus (HCV) infection based on hepatitis C antibody blood test at the screening visit
The subject has serologic evidence of human immunodeficiency virus (HIV) infection based on HIV antigen/antibody test at the screening visit
The subject has a platelet count less than 50,000 per microliter (mL) at the screening visit
The subject has a creatinine clearance less than 30 mL/minute at the screening visit
The subject has a history or evidence of a malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma) within the 2 years prior to the screening visit
The subject has had any other unstable/uncontrolled medical illness within 12 weeks prior to the screening visit such that, in the judgment of the investigator, participation in the trial would pose a significant medical risk to the subject
The subject has significant visual or auditory impairment, or limited English proficiency, that in the investigator's opinion would preclude collection of outcome measures
The subject has any contraindication to or inability to tolerate brain MRIs (e.g., a pacemaker or any other implanted device or condition that would preclude proximity to a strong magnetic field)
The subject has any contraindication to or inability to tolerate a PET scan (includes current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the subject in any given year would exceed acceptable limits of annual and total dose)
The subject has a history of allergy to dexamethasone, diphenhydramine, acetaminophen, montelukast, or acyclovir
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