A Phase 3 interventional study of Ofatumumab combined with daratumumab and Ofatumumab in Anti-N-Methyl-D-Aspartate Receptor Encephalitis, sponsored by The First People's Hospital of Changzhou. Recruiting at 2 sites in China. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-06-09.
Sponsored by The First People's Hospital of Changzhou · Phase 3, Interventional, and Treatment
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.
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.
123 studies on the registry are indexed under Autoimmune Diseases of the Nervous System; 59 are open to participants now.
This study's planned enrollment of 200 is above the median of 40 across 63 interventional studies indexed under Autoimmune Diseases of the Nervous System.
Browse Autoimmune Diseases of the Nervous System studies →The First People's Hospital of Changzhou is the lead sponsor of 28 studies on the registry; 12 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Any of the following at screening (one repeat test may be performed during the same screening period to confirm results prior to randomization):
(AST) > 2.5 × (ULN)
Alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN)
Total > 1.5 × ULN (unless due to Gilbert's syndrome)
count \< 75,000/μL (or \< 75 × 109/L)
\< 8 g/dL (or \< 80 g/L)
Total white blood cell count \< 2,500 cells/mm3
Total immunoglobulins \< 600 mg/dL
\< 1200 cells/μL
\< 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 ).
A known history of primary immunodeficiency (congenital or acquired) or underlying conditions, such as (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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 group received subcutaneous injection of ofatumumab at weeks 0, 1, 2, 4, 8, 12, 16, 20, and 24
Drug: Ofatumumab
At least two cycles of intravenous immunoglobulin/plasma exchange therapy
Drug: Repeated intravenous immunoglobulin/plasma exchange therapy
Drug pages: Ofatumumab · Daratumumab
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.
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
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
mRS score at 16 weeks
mRS score at 16 weeks
Time frame: After 16 weeks of treatment
CASE score at 16 weeks
CASE score at 16 weeks
Time frame: After 16 weeks of treatment
Incidence of adverse events
Incidence of adverse events
Time frame: After 48 weeks of treatment
Plan to share: Undecided
Started Nov 2024 (actual). Primary completion is estimated for Nov 2026, 24 months after the start.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Ofatumumab · Daratumumab
Autoimmune Diseases of the Nervous System →
The First People's Hospital of Changzhou