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

Tianjin Medical University

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Neuromyelitis Optica; NMO Spectrum Disorder; Neuromyelitis Optica Spectrum Disorder

Treatments: Drug: Daratumumab; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05403138

2022023

Details and patient eligibility

About

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.

Enrollment: 135 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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135 participants in 2 patient groups, including a placebo group

Daratumumab

Experimental group

Description:

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.

Treatment:

Drug: Daratumumab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo