Neuromyelitis OpticaPhase 2/3DAWNNCT05403138
Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders
A Phase 2/3 study testing Daratumumab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Tianjin Medical University General Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder, NMO Spectrum Disorder
- What is being tested?
- Daratumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2022to 1 Dec 2025
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants ≥ 18 years old.
- Diagnosis of NMO or NMOSD.
- Anti-AQP4 antibody seropositive.
- 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.
- Expanded Disability Status Scale score ≤ 7.5.
- Patients must give written informed consent.
Who cannot join
- Use of intravenous steroid pulse therapy or intravenous immunoglobulin or plasma exchange/adsorption within 3 weeks prior to Screening.
- Use of tocilizumab, satralizumab, belimumab, ofatumumab within 1 months prior to Screening.
- Patients treated with oral immunosuppressive agents other than steroids (e.g. azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclosporine in the 3 months prior to allocation.
- Use of rituximab or inebilizumab within 6 months prior to Screening.
- Patients infected with hepatitis B or C virus, or human immunodeficiency virus, or those having active infectious diseases.
- Patients with a severe chronic infection or a history of recurrent infections.
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- Patients with a history of radiation treatment (whole body irradiation or lymphoid irradiation) or stem cell transplantation.
- Patients who are pregnant or breast-feeding.
- Patients who are participating in other clinical trials for NMOSD.
- Patients diagnosed with cancer.
Trial locations and contacts
1 site in 1 country.
China1 site
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
About this study
Official title: 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.
- Being tested
- Daratumumab, Placebo
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
Also called Darzalex
Induction Phase: (8mg/kg) via intravenous (IV) evey 2 weeks for two cycles. Maintenance Phase: (4mg/kg) IV every 4 weeks.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab | Experimental | 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. Receives: Drug: Daratumumab |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With An Adjudicated On-trial Relapse
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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Secondary outcomes (15)
Adjudicated On-trial Annualized Relapse Rate (ARR)
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.
Measured: 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
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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Change From Baseline in Best Corrected Binocular Visual Acuity to the 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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the 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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Blood AQP4-IgG Concentration Over Time
Blood AQP4-IgG Concentration was measured by Cell-Based Assay (CBA).
Measured: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Antibody-Secreting Cells (ASCs) Over Time
Percentage of Blood ASCs was measured by flow cytometry.
Measured: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Neurofilament Light Chain (NFL) Over Time
Percentage of Blood NFL was measured with Simoa (Single-molecule array).
Measured: Baseline, Weeks 2, 4, 8, 12, 24, 48
Percentage of Blood Glial Fibrillary Acidic Protein (GFAP) Over Time
Percentage of Blood GFAP was measured with Simoa (Single-molecule array).
Measured: Baseline, Weeks 2, 4, 8, 12, 24, 48
Change From Baseline In Modified Rankin Scale (mRS) Score At 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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Change From Baseline In Hauser Ambulation Index (HAI) Score At 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.
Measured: 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
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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Change From Baseline In EuroQoL EQ-5D Index Score At 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.
Measured: 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
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.
Measured: Baseline, Up To 52 Weeks (End of Study)
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Measured: Baseline, Up To 52 Weeks (End of Study)
Number of Participants With Adverse Events Serious Adverse Events (SAEs)
A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization
Measured: Baseline, Up To 52 Weeks (End of Study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2022
- Study start1 Nov 2022
- Primary completion1 Nov 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromyelitis OpticaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu-Dong Shi, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05403138
- Sponsor's protocol ID
- 2022023
- Acronym
- DAWN
- Status last verified
- Mar 2025
- First submitted
- 30 May 2022
- Last updated
- 30 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05403138
- Acronym / sponsor ID
- DAWN / 2022023
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 1 Nov 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 3 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daratumumab | Experimental | Drug: DaratumumabInduction 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female participants ≥ 18 years old.
- Diagnosis of NMO or NMOSD.
- Anti-AQP4 antibody seropositive.
- 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.
- Expanded Disability Status Scale score ≤ 7.5.
Key exclusion criteria (10 listed)
- Use of intravenous steroid pulse therapy or intravenous immunoglobulin or plasma exchange/adsorption within 3 weeks prior to Screening.
- Use of tocilizumab, satralizumab, belimumab, ofatumumab within 1 months prior to Screening.
- Patients treated with oral immunosuppressive agents other than steroids (e.g. azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclosporine in the 3 months prior to allocation.
- Use of rituximab or inebilizumab within 6 months prior to Screening.
- Patients infected with hepatitis B or C virus, or human immunodeficiency virus, or those having active infectious diseases.
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 |
|---|---|---|
| DaratumumabAlso: DarzalexInduction Phase: (8mg/kg) via intravenous (IV) evey 2 weeks for two cycles. Maintenance Phase: (4mg/kg) IV every 4 weeks. | Drug | Daratumumab |
| PlaceboInduction Phase: matching placebo (8mg/kg) via intravenous (IV) every 2 weeks for two cycles; Maintenance Phase: matching placebo (4mg/kg) IV every 4 weeks. | Drug | Placebo |
Primary outcome
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.
15 secondary outcomes
Adjudicated On-trial Annualized Relapse Rate (ARR)
Time frame: 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)
Change From Baseline in Best Corrected Binocular Visual Acuity to the end of study
Time frame: 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)
Blood AQP4-IgG Concentration Over Time
Time frame: 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 Neurofilament Light Chain (NFL) Over Time
Time frame: 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
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
Time frame: 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)
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)
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
Time frame: 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)
Number of Participants With Adverse Events (AEs)
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Individual participant dataSharing planned: No
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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 2/3 study testing Daratumumab in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, run by Tianjin Medical University General Hospital at 1 site in China.
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 6 inclusion and 10 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: under way, not looking for participants, as of the sponsor's last update on 30 Mar 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 China. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Participants With An Adjudicated On-trial Relapse (time frame: Baseline, Up To 52 Weeks (End of Study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2025.