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

NCT06867991 | Recruiting Phase 3 DMC

• 1 other identifier: RADIA-2024-11
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Keywords

Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Ofatumumab; Daratumumab; severe autoimmune encephalitis

Outcome Measures

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

  week 16

Secondary Outcomes (3)

• mRS score at 16 weeks

  After 16 weeks of treatment

• CASE score at 16 weeks

  After 16 weeks of treatment

• Incidence of adverse events

  After 48 weeks of treatment

Study Arms (3)

B cell depleting agent（ofatumumab）combined with daratumumab treatment group

EXPERIMENTAL

The group receiving B cell depletion plus daratumumab 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 effect of up to 24 cycles of daratumumab

Drug: Ofatumumab combined with daratumumab

Ofatumumab treatment group

ACTIVE COMPARATOR

Ofatumumab group received subcutaneous injection of ofatumumab at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24

Drug: Ofatumumab

Repeated intravenous immunoglobulin/plasma exchange therapy group

ACTIVE COMPARATOR

At least two cycles of intravenous immunoglobulin/plasma exchange therapy

Drug: Repeated intravenous immunoglobulin/plasma exchange therapy

Interventions

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.

B cell depleting agent（ofatumumab）combined with daratumumab treatment group

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.

Ofatumumab treatment group

Repeated intravenous immunoglobulin/plasma exchange therapy DRUG

Repeated intravenous immunoglobulin/plasma exchange therapy

Repeated intravenous immunoglobulin/plasma exchange therapy group

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Informed consent or guardian signed informed consent

You may not qualify if:

• 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.
• Any of the following at screening (one repeat test may be performed during the same screening period to confirm results prior to randomization):
• Aspartate aminotransferase (AST) \> 2.5 × upper limit of normal (ULN)
• Alanine aminotransferase (ALT) \> 2.5 × upper limit of normal (ULN)
• Total bilirubin \> 1.5 × ULN (unless due to Gilbert's syndrome)
• Platelet count \< 75,000/μL (or \< 75 × 109/L)
• Hemoglobin \< 8 g/dL (or \< 80 g/L)
• Total white blood cell count \< 2,500 cells/mm3
• Total immunoglobulins \< 600 mg/dL
• Absolute neutrophil count \< 1200 cells/μL
• CD4 T lymphocyte count \< 300 cells/µL
• Receipt of any experimental B cell depleting agent, unless CD19 B Cell levels have returned to above the lower limit of normal before randomization A history of severe drug allergies or anaphylaxis to two or more foods or drugs (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamines, and methylprednisolone or equivalent glucocorticoids).

Sponsors & Collaborators

• The First People's Hospital of Changzhou: lead

Study Sites (2)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

RECRUITING

The First People's Hospital of Changzhou

Changzhou, Jiangsu, 213000, China

RECRUITING

MeSH Terms

Conditions

Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoimmune Diseases of the Nervous System

Interventions

daratumumab; ofatumumab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Wei Xie

CONTACT

+86051968872122; 13706121930@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 10, 2025
• Study Start: November 8, 2024
• Primary Completion (Estimated): November 8, 2026
• Study Completion (Estimated): November 8, 2027
• Last Updated: July 15, 2025

Record last verified: 2025-07

Locations

CN (2)