Alzheimer DiseasePhase 2DARZADNCT04070378
Study of Daratumumab in Patients With Mild to Moderate Alzheimer's Disease
A Phase 2 study testing Daratumumab Injection in people with Alzheimer Disease, run by Marc L Gordon, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Daratumumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2019to 15 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Litwin-Zucker Research Center
Manhasset, New York, 11030
About this study
Official title: An Open-Label, Pilot Study of Daratumumab SC in Patients With Mild to Moderate Alzheimer's Disease
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.
Read the detailed 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.
- Conditions
- Alzheimer Disease
- Being tested
- Daratumumab Injection
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daratumumab InjectionDrug
Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
| Study group | Role | What they receive |
|---|---|---|
| Open-label Treatment | Experimental | 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. During the treatment phase, eligible subjects will receive daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion over 3-5 minutes (15 mL) once weekly for 8 weeks followed by daratumumab SC 1800 mg every 2 weeks for 16 weeks. Receives: Drug: Daratumumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With an Improvement of ≥ 4 Points on the ADAS-cog/11
The standard 11-item version of the Alzheimer's Disease Assessment Scale, cognitive subscale score (ADAS-cog/11) includes both subject-completed tests and observer-based assessments. Specific tasks include Word Recall, Naming Objects and Fingers, Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition, and Language. The score ranges from 0 to 70 with each point representing a performance error and higher scores reflecting worse performance. An improvement (decrease) of ≥ 4 points in ADAS-cog/11 score has been deemed to be clinically meaningful.
Measured: 25 weeks
Secondary outcomes (6)
The Number of Subjects Who Are Unchanged or Improved From Baseline on ADAS-cog/12 Score
The 12-item version of the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog/12) adds a delayed word recall task, scored from 0 to 10. The ADAS-Cog/12 score is the total of the ADAS-Cog/11 plus the delayed recall score, and therefore has a range of 0 to 80. Higher scores reflect worse performance.
Measured: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the MMSE
The Mini-Mental State Examination (MMSE) is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores range from 0 (most impaired) to 30 (no impairment).
Measured: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the CDR-SB
The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is a clinical global rating scale requiring the interviewing of both the subject and a study partner who knows and has contact with the subject. The CDR-SB is a clinician-directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the individual. The range of scores is from 0-18, with higher scores being worse.
Measured: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the ADCOMS
The AD Composite Score (ADCOMS) is derived from a weighted combination of selected items from the ADAS-cog/12, MMSE, and CDR-SB. The range of the ADCOMS is between 0 and 1.97. A higher score is indicative of greater impairment.
Measured: 25 weeks
Treatment Emergent Adverse Effects
The proportion of subjects with treatment-emergent adverse effects from initial treatment through final follow-up study visit.
Measured: 35 weeks
Treatment Emergent Serious Adverse Effects
The proportion of subjects with treatment-emergent serious adverse effects from initial treatment through final follow-up study visit.
Measured: 35 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start6 Nov 2019
- Primary completion8 Jun 2023
- Study completion15 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label treatment group.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marc L Gordon, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Responsible party
- Sponsor-investigator, Marc L Gordon, MD, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04070378
- Sponsor's protocol ID
- 19-0619
- Acronym
- DARZAD
- Status last verified
- Nov 2023
- First submitted
- 22 Aug 2019
- Last updated
- 14 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: This study will comply with the Clinical Trials Registration and Results Information Submission rule. Result information from this trial will be submitted to ClinicalTrials.gov.
Publications
Zhang SQ, Lee J, Pan JP, Enger R, Hrubos-Strom H, Musiek ES, Fang EF, Le W. NAD+-circadian rhythm coupling in dementia. Alzheimers Dement. 2026 May;22(5):e71360. doi: 10.1002/alz.71360.
PubMed 42063312
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Pilot Study of Daratumumab SC in Patients With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04070378
- Acronym / sponsor ID
- DARZAD / 19-0619
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Marc L Gordon, MDUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Study start
- 6 Nov 2019 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 15 Aug 2023 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 29 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label treatment group.
| Arm | Type | Receives |
|---|---|---|
| Open-label Treatment | Experimental | Drug: Daratumumab InjectionThis 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. During the treatment phase, eligible subjects will receive daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion over 3-5 minutes (15 mL) once weekly for 8 weeks followed by daratumumab SC 1800 mg every 2 weeks for 16 weeks. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daratumumab InjectionDaratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion | Drug | Open-label Treatment |
Primary outcome
Number of Participants With an Improvement of ≥ 4 Points on the ADAS-cog/11
Time frame: 25 weeks
The standard 11-item version of the Alzheimer's Disease Assessment Scale, cognitive subscale score (ADAS-cog/11) includes both subject-completed tests and observer-based assessments. Specific tasks include Word Recall, Naming Objects and Fingers, Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition, and Language. The score ranges from 0 to 70 with each point representing a performance error and higher scores reflecting worse performance. An improvement (decrease) of ≥ 4 points in ADAS-cog/11 score has been deemed to be clinically meaningful.
6 secondary outcomes
The Number of Subjects Who Are Unchanged or Improved From Baseline on ADAS-cog/12 Score
Time frame: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the MMSE
Time frame: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the CDR-SB
Time frame: 25 weeks
The Number of Subjects Who Are Unchanged or Improved From Baseline on the ADCOMS
Time frame: 25 weeks
Treatment Emergent Adverse Effects
Time frame: 35 weeks
Treatment Emergent Serious Adverse Effects
Time frame: 35 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42063312Zhang SQ, Lee J, Pan JP, Enger R, Hrubos-Strom H, Musiek ES, Fang EF, Le W. NAD+-circadian rhythm coupling in dementia. Alzheimers Dement. 2026 May;22(5):e71360. doi: 10.1002/alz.71360.
- Individual participant dataSharing planned: No. This study will comply with the Clinical Trials Registration and Results Information Submission rule. Result information from this trial will be submitted to ClinicalTrials.gov.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab Injection in people with Alzheimer Disease, run by Marc L Gordon, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With an Improvement of ≥ 4 Points on the ADAS-cog/11 (time frame: 25 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04070378, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2025.