Trial Outcomes & Findings for Study of Daratumumab in Patients With Mild to Moderate Alzheimer's Disease (NCT NCT04070378)

Last Updated: 2025-11-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

25 weeks

Results posted on

2025-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	Open-label Treatment 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Overall Study STARTED	16
Overall Study Subjects who received at least one dose of study drug.	9
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label Treatment 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Overall Study Withdrawal by Subject	2
Overall Study Screen Failure	6
Overall Study Physician Decision	1
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label Treatment n=16 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Age, Categorical <=18 years	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=10 Participants
Age, Categorical >=65 years	10 Participants n=10 Participants
Age, Continuous	67.46 years n=10 Participants
Sex: Female, Male Female	8 Participants n=10 Participants
Sex: Female, Male Male	8 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants
Race (NIH/OMB) Asian	3 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=10 Participants
Race (NIH/OMB) White	13 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants
Region of Enrollment United States	16 participants n=10 Participants

PRIMARY outcome

Timeframe: 25 weeks

Population: A total of 16 subjects were screened, with 6 screen failures, 1 subject who withdrew consent prior to treatment, 1 subject who withdrew consent after 3 treatment visits, 1 subject withdrawn by the investigator after having missed 7 consecutive visits due to the COVID pandemic, and 1 subject withdrawn due to a possibly related adverse event, leaving 6 evaluable subjects who completed treatment.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=6 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Number of Participants With an Improvement of ≥ 4 Points on the ADAS-cog/11	0 responders

SECONDARY outcome

Timeframe: 25 weeks

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.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=6 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
The Number of Subjects Who Are Unchanged or Improved From Baseline on ADAS-cog/12 Score	0 responders

SECONDARY outcome

Timeframe: 25 weeks

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).

Outcome measures

Outcome measures
Measure	Open-label Treatment n=6 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
The Number of Subjects Who Are Unchanged or Improved From Baseline on the MMSE	0 responders

SECONDARY outcome

Timeframe: 25 weeks

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.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=6 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
The Number of Subjects Who Are Unchanged or Improved From Baseline on the CDR-SB	0 responders

SECONDARY outcome

Timeframe: 25 weeks

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.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=6 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
The Number of Subjects Who Are Unchanged or Improved From Baseline on the ADCOMS	0 responders

SECONDARY outcome

Timeframe: 35 weeks

Population: Nine participants were treated with study medication. Four subjects experienced adverse events that were either definitely or possibly attributed to the medication by the investigator.

The proportion of subjects with treatment-emergent adverse effects from initial treatment through final follow-up study visit.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=9 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Treatment Emergent Adverse Effects	4 Participants

SECONDARY outcome

Timeframe: 35 weeks

Population: Nine subjects received at least one dose of study medication.

The proportion of subjects with treatment-emergent serious adverse effects from initial treatment through final follow-up study visit.

Outcome measures

Outcome measures
Measure	Open-label Treatment n=9 Participants 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Treatment Emergent Serious Adverse Effects	1 Participants

Adverse Events

Open-label Treatment

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-label Treatment n=9 participants at risk 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Respiratory, thoracic and mediastinal disorders COVID-19 pneumonia	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).

Other adverse events

Other adverse events
Measure	Open-label Treatment n=9 participants at risk 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. Daratumumab Injection: Daratumumab SC 1800 mg (daratumumab 1800 mg with rHuPH20 30,000 units) subcutaneous infusion
Skin and subcutaneous tissue disorders Infusion reaction; urticarial rash	44.4% 4/9 • Number of events 4 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Respiratory, thoracic and mediastinal disorders cough	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Skin and subcutaneous tissue disorders Bilateral cheek, ear, chin erythematous hives with mild swelling and itching	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Nervous system disorders Brief transient unresponsiveness	11.1% 1/9 • Number of events 2 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Skin and subcutaneous tissue disorders Burn on lower back	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Immune system disorders Vaccine reaction	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Gastrointestinal disorders diarrhea	22.2% 2/9 • Number of events 2 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Respiratory, thoracic and mediastinal disorders Difficulty breathing	22.2% 2/9 • Number of events 2 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Skin and subcutaneous tissue disorders Dog bite	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Hepatobiliary disorders Elevated Liver Transaminases	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Psychiatric disorders Increased agitation	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Fall	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Infections and infestations fever	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Eye disorders Floaters	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Headache	44.4% 4/9 • Number of events 12 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Increased sleepiness	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Insomnia	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Cardiac disorders Intermittent palpitations	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Gastrointestinal disorders Intermittent nausea/upset stomach	11.1% 1/9 • Number of events 2 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Renal and urinary disorders Overactive bladder	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Musculoskeletal and connective tissue disorders Lower back pain/pull	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Repetitive sneezing	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Runny nose/itchy eyes	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Scratchy throat	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Cardiac disorders Supraventricular tachycardia	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Renal and urinary disorders UTI	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
Skin and subcutaneous tissue disorders Urticaria	77.8% 7/9 • Number of events 10 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).
General disorders Weight loss	11.1% 1/9 • Number of events 1 • Adverse event data were collected from the time of consent through completion of the final study follow-up visit (approximately 10 months).

Additional Information

Marc L Gordon, MD

The Feinstein Institutes for Medical Research

Phone: (516) 562-3492

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place