ClinicalTrials.gov record NCT06867991

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 3A later-stage study, usually with more participants, designed to give stronger evidence about how well a treatment works and how safe it is. It often compares the treatment with standard care or a placebo, and results may support an application for approval.
Age12 years old and older
SexAll
LocationChina
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This randomized phase 3 trial compares three active treatment approaches for anti‑NMDAR encephalitis. It tests subcutaneous ofatumumab alone, ofatumumab plus intravenous daratumumab, and repeated IVIG or plasma exchange. The study is for people aged 12 years and older who have already received standard first‑line therapy.

What it is studying. The study evaluates the safety and effects of combining B‑cell depletion with ofatumumab and plasma‑cell depletion with daratumumab, compared with ofatumumab alone or repeated IVIG/plasma exchange. Primary measurement is time to reach a good functional outcome (modified Rankin Scale score 0–2) by week 16; other measures include CASE score and adverse events.

What the researchers hope to learn. To determine the safety and efficacy of adding daratumumab to ofatumumab compared with ofatumumab alone or repeated IVIG/plasma exchange in anti‑NMDAR encephalitis. Key scientific goals include time to achieve mRS ≤2 at week 16, mRS and CASE scores at 16 weeks, and incidence of adverse events through 48 weeks.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Ofatumumab combined with daratumumab
  • Ofatumumab
  • Repeated intravenous immunoglobulin/plasma exchange therapy

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • 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

Exclusion criteria

  • 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).
  • A known history of primary immunodeficiency (congenital or acquired) or underlying conditions, such as human immunodeficiency virus (HIV) infection or splenectomy, that predispose the participant to infection.
  • Any of the following received within 3 months before randomization Natalizumab (Tysabri®) Cyclosporin Methotrexate Mitoxantrone Cyclophosphamide Azathioprine
  • Confirmed positive hepatitis B serology (hepatitis B surface antigen and core antigen) and/or positive hepatitis C PCR at screening.
  • History of cancer, other than ovarian or extraovarian teratoma (also known as dermoid cyst) or germ cell tumor, or cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma. Treatment of squamous cell carcinoma and basal cell carcinoma should have documented successful curative treatment more than 3 months before randomization.
  • Received any live or attenuated vaccine (inactivated vaccine is acceptable) within 3 weeks before enrollment.
  • Received BCG vaccine within 1 year before enrollment.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Autoimmune encephalitis (AE) is a broad spectrum of immune-mediated neuropsychiatric diseases, usually associated with antibodies against surface proteins, ion channels, synapses or intracellular proteins of neuronal cells. Anti-N-methyl-D-aspartate receptro (NMDAR) encephalitis is the most common type of AE.The clinical manifestations include behavioral changes, psychiatric symptoms, epileptic seizures, memory and cognitive deficits, abnormal movements, autonomic dysfunction and decreased consciousness. Most children and adult patients present with a syndrome that combines the above symptoms and can be severe. Early initiation of immunotherapy is necessary to improve clinical prognosis and reduce its recurrence. However, no disease-modifying therapy specifically for AE has been approved. A variety of therapies have emerged for severe autoimmune encephalitis, including anti-CD20 monoclonal antibody rituximab, proteasome inhibitor bortezomib, anti-CD38 monoclonal antibody daratumumab, anti-IL-6R monoclonal antibody tocilizumab, low-dose IL-2, and intrathecal methotrexate. The evidence for the efficacy of these drugs mostly comes from case reports, and there are currently no high-quality randomized controlled clinical studies reported. Studies have found that anti-NMDAR antibody is produced by autoreactive B cells and plasma cells. Among these cells, long-lived plasma cells in the intrathecal, meningeal, and brain parenchyma are responsible for the production of pathogenic antibodies in severe cases. The B cell-depleting therapeutic antibody rituximab targets CD20-positive B cells. CD138-positive plasma cells lack CD20 surface receptors, are not targeted by rituximab, and are also resistant to other immunosuppressive therapies. Daratumumab is an anti-CD38 antibody that can target long-lived plasma cells and has shown good therapeutic responses in autoimmune hemolytic anemia, systemic lupus erythematosus, and autoimmune encephalitis, with an acceptable safety profile. Daratumumab not only works by clearing plasma cells, but also regulates certain T cell functions. RADIA study is an investigator-initiated, randomized, controlled, open-label, multicenter clinical trial to investigate the safety and efficacy of anti-CD20 mAb ofatumumab in combination of anti-CD38 mAb daratumumab in patients with severe anti-NMDAR encephalitis.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

All participants must have started acute first‑line therapy before randomization. After randomization they will receive one of three study approaches: subcutaneous ofatumumab injections on a schedule through week 24; ofatumumab plus intravenous daratumumab given after ofatumumab (daratumumab doses at early and later weeks, with up to 24 cycles investigated); or repeated IVIG or plasma exchange. Participants on corticosteroids follow a standard taper beginning 4 weeks after randomization. Expect clinic visits for drug administration (injections or IV infusions), monitoring and safety checks, and outcome assessments including mRS and CASE scores; adverse‑event monitoring continues during treatment and through follow‑up (safety outcomes include events assessed up to 48 weeks).

How the study is structured. A randomized, parallel‑group, single‑masked phase 3 interventional trial. Participants are assigned to one of three active treatment arms and receive scheduled drug treatments over weeks; outcomes are assessed at 16 weeks and adverse events followed through 48 weeks.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Does it apply to my diagnosis?
  • The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on autoimmune encephalitis

Clinical trials40 trials listed for autoimmune encephalitisEvery trial the registry lists for autoimmune encephalitis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in autoimmune encephalitis researchLatest monthly update: September 2026. Includes: Efgartigimod reports. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Nov 8, 2024
Primary completion
Nov 8, 2026 (estimated)
Study completion
Nov 8, 2027 (estimated)
Target enrollment
200 participants (estimated)
Last updated on registry
Jun 9, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
The First People's Hospital of Changzhou

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (2)

Terms used on this page · explanations by MedicalUpdates.ai

Informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
half-lives
The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
randomization
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
at screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
Absolute neutrophil count
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
glucocorticoids
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
intrathecal
Given by injection into the fluid around the spinal cord, usually through a lumbar puncture.
immunosuppressive
A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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