Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders (DAWN)

March 28, 2025 updated by: Fu-Dong Shi, Tianjin Medical University General Hospital

A Multi-center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders (NMOSD)

The objectives of this time-to-event study are to assess the efficacy and safety of Daratumumab as compared with placebo in participants with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive. NMOSD is an autoimmune disease of the central nervous system that predominantly affects the spinal cord, optic nerves, and area postrema. It is usually mediated by the pathogenic AQP4-IgG. Antibody-secreting cells (ASCs) have been recognized as essential sources of AQP4-IgG. CD38 is a glycoprotein that is highly expressed on ASCs. Daratumumab, a CD38-directed monoclonal antibody, has been shown to decrease the levels of autoantibodies in lupus, myasthenia gravis, or autoimmune encephalitis. This randomized controlled study aims to evaluate the therapeutic potential of daratumumab in NMOSD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
135

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Fu-Dong Shi, M.D., Ph.D.
  • Phone Number: +8602260814587
  • Email: fshi@tmu.edu.cn

Study Contact Backup

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300052
        • Tianjin Medical University General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female participants ≥ 18 years old.
  2. Diagnosis of NMO or NMOSD.
  3. Anti-AQP4 antibody seropositive.
  4. Historical relapse of at least 1 relapses in the last 12 months or 2 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
  5. Expanded Disability Status Scale score ≤ 7.5.
  6. Patients must give written informed consent.

Exclusion Criteria:

  1. Use of intravenous steroid pulse therapy or intravenous immunoglobulin or plasma exchange/adsorption within 3 weeks prior to Screening.
  2. Use of tocilizumab, satralizumab, belimumab, ofatumumab within 1 months prior to Screening.
  3. Patients treated with oral immunosuppressive agents other than steroids (e.g. azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclosporine in the 3 months prior to allocation.
  4. Use of rituximab or inebilizumab within 6 months prior to Screening.
  5. Patients infected with hepatitis B or C virus, or human immunodeficiency virus, or those having active infectious diseases.
  6. Patients with a severe chronic infection or a history of recurrent infections.
  7. Patients with a history of radiation treatment (whole body irradiation or lymphoid irradiation) or stem cell transplantation.
  8. Patients who are pregnant or breast-feeding.
  9. Patients who are participating in other clinical trials for NMOSD.
  10. Patients diagnosed with cancer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Daratumumab
Induction Period: Participants received daratumumab (8mg/kg) via intravenous (IV) every 2 weeks for two cycles. This was followed by the Maintenance Period: Participants received daratumumab (4mg/kg) via IV infusion every 4 weeks from the third dose (Week 4) onwards.
Drug: Daratumumab
Induction Phase: (8mg/kg) via intravenous (IV) evey 2 weeks for two cycles. Maintenance Phase: (4mg/kg) IV every 4 weeks.
Other Names:
  • Darzalex
Placebo Comparator: Placebo
Placebo contains the same buffer components without the active ingredient. Induction Period: Participants received matching placebo (8mg/kg) via intravenous (IV) every 2 weeks for two cycles. This was followed by the Maintenance Period: Participants received matching placebo (4mg/kg) via IV infusion every 4 weeks from the third dose (Week 4) onwards.
Drug: Placebo
Induction Phase: matching placebo (8mg/kg) via intravenous (IV) every 2 weeks for two cycles; Maintenance Phase: matching placebo (4mg/kg) IV every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Participants With An Adjudicated On-trial Relapse
Time Frame: Baseline, Up To 52 Weeks (End of Study)
An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
Baseline, Up To 52 Weeks (End of Study)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adjudicated On-trial Annualized Relapse Rate (ARR)
Time Frame: Baseline, Up To 52 Weeks (End of Study)
The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of patient years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression adjusted for randomization strata and historical ARR in 24 months prior to Screening.
Baseline, Up To 52 Weeks (End of Study)
Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
Disease-related disability was measured by the EDSS. The EDSS was an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline in Best Corrected Binocular Visual Acuity to the end of study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
Best corrected binocular visual acuity was measure with Early Treatment Diabetic Retinopathy Study (ETDRS) chart held at a distance of 2.52 meters.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the end of study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
Low-contrast visual acuity test was used to determine the number of letters that can be read on a standardized low-contrast retro-illuminated 2.5% Sloan letter chart held at a distance of 2.52 meters. Binocular score was the number of letters read correctly on the chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision.
Baseline, Up To 52 Weeks (End of Study)
Blood AQP4-IgG Concentration Over Time
Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48
Blood AQP4-IgG Concentration was measured by Cell-Based Assay (CBA).
Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Antibody-Secreting Cells (ASCs) Over Time
Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood ASCs was measured by flow cytometry.
Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Neurofilament Light Chain (NFL) Over Time
Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood NFL was measured with Simoa (Single-molecule array).
Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Glial Fibrillary Acidic Protein (GFAP) Over Time
Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood GFAP was measured with Simoa (Single-molecule array).
Baseline, Weeks 2, 4, 8, 12, 24, 48
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
Disease-related disability was measured by the mRS score. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered from a neurological disability. The scale ranges from 0 (no disability) to 6 (death) in whole-point increments. A decrease in score indicates improvement.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
The HAI was used to evaluate gait and assess the time and effort used by the participant to walk 25 feet (8 meters). The scale ranges from 0 to 9, with 0 being the best score (asymptomatic; fully ambulatory with no assistance) and 9 being the worst (restricted to wheel chair; unable to transfer self independently). A decrease in score indicates improvement.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
The EuroQoL EQ-5D was a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Assessments were made using the EQ-5D Visual Analogue Scale, which captures the self-rating of current health status using a visual "thermometer" with the endpoints of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom. An increase in score indicates improvement.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
Time Frame: Baseline, Up To 52 Weeks (End of Study)
The EuroQoL EQ-5D was a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Index scores range from less than 0 to 1, with higher scores representing a better health status.
Baseline, Up To 52 Weeks (End of Study)
Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period
Time Frame: Baseline, Up To 52 Weeks (End of Study)
The T25W was an assessment of walking ability. The time (in seconds) that the participant took to walk 25 feet was measured. Speed is calculated as 1/Timed 25-Foot Walk where time is measured in seconds. A positive change from baseline indicates an improvement.
Baseline, Up To 52 Weeks (End of Study)
Number of Participants With Adverse Events (AEs)
Time Frame: Baseline, Up To 52 Weeks (End of Study)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Baseline, Up To 52 Weeks (End of Study)
Number of Participants With Adverse Events Serious Adverse Events (SAEs)
Time Frame: Baseline, Up To 52 Weeks (End of Study)
A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization
Baseline, Up To 52 Weeks (End of Study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tianjin Medical University General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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