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

NCT04070378 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-0619
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  25 weeks

Secondary Outcomes (6)

• The Number of Subjects Who Are Unchanged or Improved From Baseline on ADAS-cog/12 Score

  25 weeks

• The Number of Subjects Who Are Unchanged or Improved From Baseline on the MMSE

  25 weeks

• The Number of Subjects Who Are Unchanged or Improved From Baseline on the CDR-SB

  25 weeks

• The Number of Subjects Who Are Unchanged or Improved From Baseline on the ADCOMS

  25 weeks

• Treatment Emergent Adverse Effects

  35 weeks

Study Arms (1)

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.

Drug: Daratumumab Injection

Interventions

Daratumumab Injection DRUG

Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion

Open-label Treatment

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Marc L Gordon, MD: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

The Litwin-Zucker Research Center

Manhasset, New York, 11030, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Marc L Gordon, MD
• Organization: The Feinstein Institutes for Medical Research

mlgordon@northwell.edu

(516) 562-3492

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology and Psychiatry

Model Details: Open-label treatment group.

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: November 6, 2019
• Primary Completion: June 8, 2023
• Study Completion: August 15, 2023
• Last Updated: November 14, 2025
• Results First Posted: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)