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Safety and Efficacy of Combined B Cell Depleting theRapy And Daratumumab In Autoimmune Encephalitis

ConditionAnti-N-Methyl-D-Aspartate Receptor Encephalitis
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age12+
SponsorThe First People's Hospital of Changzhou

About this trial

Autoimmune encephalitis is an autoimmune disease of the central nervous system that targets neuronal autoantigens. Anti-neuronal autoantibodies are produced in patients, with anti-NMDAR antibody being the most common.Anti-NMDAR encephalitis can be severe and life-threatening. Anti-NMDAR autoantibodies against neurons are pathogenic and are mainly produced by autoreactive B cells and plasma cells. Therefore, early elimination of these abnormal immune cells is crucial for rapid improvement of the patient's condition. This study aims to explore the efficacy and safety of B cell depletion therapy (ofatumumab) followed by plasma cell depletion therapy (daratumumab) in the treatment of severe anti-NMDAR autoimmune encephalitis.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged 12 years and above

Meet the diagnosis of autoimmune encephalitis and the target antigen is a neuronal surface antigen

Have received at least 3 days of 500-1000mg high-dose methylprednisolone impulse treatment and IVIG (0.4g/kg/d for 5 consecutive days) or at least 5 plasma exchange/immunoadsorption or at least 2 times of efgartigimod treatment

mRS ≥ 3 points and neuropsychiatric manifestations inadequate to symptomatic treatment

Disqualifiers

Severe active or chronic infection in the opinion of the investigator.

Concurrently/previously participated in another clinical study involving investigational therapy within 4 weeks or 5 published half-lives of the investigational therapy (whichever is longer) before randomization.

Women who are lactating or pregnant, or intend to become pregnant at any time within six months from study enrollment to the last dose of study drug.

Known history of allergy or reaction to any component of the investigational drug formulation, or history of allergic reaction after any biological treatment.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ofatumumab combined with daratumumab

    Drug

    All participants will begin acute first-line therapy prior to randomization, and participants who were receiving oral or intravenous corticosteroids at baseline will need to taper their doses according to a standard taper schedule starting 4 weeks after randomization (week 4). Patients will be randomly assigned to receive ofatumumab followed by daratumumab or ofatumumab followed by repeated intravenous globulin. The ofatumumab group will receive subcutaneous ofatumumab at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24, while the ofatumumab-daratumumab group will receive daratumumab intravenously (on the second day of ofatumumab) in addition to ofatumumab, with a dose of 8 mg/kg at weeks 0, 1, 2, and 4, and a dose of 4 mg/kg at weeks 8, 12, 16, 20, and 24. The study will investigate the effects of up to 24 cycles of daratumumab.

  • Ofatumumab

    Drug

    All participants were started on acute first-line therapy before randomization, and participants who were receiving oral or intravenous glucocorticoids at baseline were required to taper their doses according to a standard taper schedule starting 4 weeks after randomization (week 4). Ofatumumab was administered subcutaneously at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24 in the ofatumumab group.

  • Repeated intravenous immunoglobulin/plasma exchange therapy

    Drug

    Repeated intravenous immunoglobulin/plasma exchange therapy

Treatment groups

200 Participants
are divided into 3 treatment groups
Group A: B cell depleting agent（ofatumumab）combined with daratumumab treatment groupExperimental treatment 1 intervention
Group B: Ofatumumab treatment groupActive comparator 1 intervention
Group C: Repeated intravenous immunoglobulin/plasma exchange therapy groupActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Time to mRS<=2, i.e. the proportion of patients with mRS scores of 0-2

Primary objective: • Patients achieve good outcome Primary endpoint: • Time to mRS\<=2, i.e. the proportion of patients with mRS scores of 0-2

Time frame
week 16

Secondary outcomes

1

mRS score at 16 weeks

mRS score at 16 weeks

Time frame
After 16 weeks of treatment
2

CASE score at 16 weeks

CASE score at 16 weeks

Time frame
After 16 weeks of treatment
3

Incidence of adverse events

Incidence of adverse events

Time frame
After 48 weeks of treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The First People's Hospital of Changzhou

Lead sponsor

Source ClinicalTrials.gov
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