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

NCT05403138 | Active Not Recruiting Phase 2

• 1 other identifier: 2022023
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder; NMO Spectrum Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Up To 52 Weeks (End of Study)

Secondary Outcomes (15)

• Adjudicated On-trial Annualized Relapse Rate (ARR)

  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

  Baseline, Up To 52 Weeks (End of Study)

• Change From Baseline in Best Corrected Binocular Visual Acuity to the end of study

  Baseline, Up To 52 Weeks (End of Study)

• Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the end of study

  Baseline, Up To 52 Weeks (End of Study)

• Blood AQP4-IgG Concentration Over Time

  Baseline, Weeks 2, 4, 8, 12, 24, 48

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Daratumumab DRUG

Induction Phase: (8mg/kg) via intravenous (IV) evey 2 weeks for two cycles. Maintenance Phase: (4mg/kg) IV every 4 weeks.

Also known as: Darzalex

Daratumumab

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: June 3, 2022
• Study Start: November 1, 2022
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)