Clinical trial NCT05403138: Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
NMO Spectrum Disorder
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2022-06-03
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Participants With An Adjudicated On-trial Relapse
timeFrame: Baseline, Up To 52 Weeks (End of Study)
Secondary outcomes:
measure: Adjudicated On-trial Annualized Relapse Rate (ARR)
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline in Best Corrected Binocular Visual Acuity to the end of study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the end of study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Blood AQP4-IgG Concentration Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 48
measure: Percentage of Blood Antibody-Secreting Cells (ASCs) Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 48
measure: Percentage of Blood Neurofilament Light Chain (NFL) Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 48
measure: Percentage of Blood Glial Fibrillary Acidic Protein (GFAP) Over Time
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 48
measure: Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline, Up To 52 Weeks (End of Study)
measure: Number of Participants With Adverse Events Serious Adverse Events (SAEs)
timeFrame: Baseline, Up To 52 Weeks (End of Study)
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
References: