Clinical trial NCT05177939: Phase III Clinical Study of NPB-01 in Patients With Autoimmune Encephalitis
Official title: Phase III Study to Evaluate the Efficacy and Safety of NPB-01 in Patients With Autoimmune Encephalitis Refractory to Steroid Pulse Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Autoimmune Encephalitis
Lead sponsor: Nihon Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-01-05
Enrollment: 40
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the efficacy and safety of NPB-01 in patients with autoimmune encephalitis refractory to steroid pulse therapy using steroid pulse therapy as a control.


Eligibility criteria: Inclusion Criteria

* \< At 1st registration \> Patients meeting the possible diagnostic criteria for autoimmune encephalitis
* \< At 1st registration \> Patients with a CASE score of 5 to 22 during the screening period
* \< At 1st registration \> Patients with autoimmune encephalitis in progress (active and requiring therapeutic intervention)
* \< At 1st registration \> IVIG therapy and steroid pulse therapy are considered necessary by the investigator.
* \< At 1st registration \> Patients aged 15 years or older at the time of informed consent
* \< At 2nd registration \> Patients who meet any of the following (1) to (6):

  1. Definite diagnostic criteria for autoimmune limbic encephalitis
  2. MRI evidence of demyelination (probable autoimmune encephalitis)
  3. Probabilistic diagnostic criteria for anti-NMDAR encephalitis
  4. Probabilistic diagnostic criteria for Bickerstaff brainstem encephalitis
  5. Probabilistic diagnostic criteria for Hashimoto's encephalopathy
  6. Diagnostic Criteria for Autoimmune Encephalitis with Negative but Probable Autoantibodies
* \< At 2nd registration \> CASE score of 5 to 22 on Day 8 of the previous treatment period
* \< At 2nd registration \> Patients who have had an inadequate response to steroid pulse therapy

Exclusion Criteria:

* \< At 1st registration \> Patients with strongly suspected infectious encephalitis
* \< At 1st registration \> Patients who received immunoglobulin preparations within 8 weeks prior to informed consent
* \< At 1st registration \> Patients who received plasma exchange within 4 weeks prior to informed consent
* \< At 1st registration \> Patients who received immunosuppressants (Rituximab, cyclophosphamide, etc.) within 4 weeks prior to informed consent
* \< At 1st registration \> Patients who have had tumor resection associated with autoimmune encephalitis within 4 weeks prior to informed consent
* \< At 1st registration \> Patients with a history of shock or hypersensitivity to the ingredients of NPB-01
* \< At 1st registration \> Patients with known IgA deficiency
* \< At 1st registration \> Patients with renal disorder
* \< At 1st registration \> Patients with a current or previous history of cerebral or cardiovascular disorders (Asymptomatic cerebral infarction and myocardial infarction that occurred more than 5 years ago are not applicable.)
* \< At 1st registration \> Patients at high risk of thromboembolism
* \< At 1st registration \> Patients with haemolytic/blood loss anaemia
* \< At 1st registration \> Immunosuppressed/immunocompromised patients
* \< At 1st registration \> Patients with decreased cardiac function
* \< At 1st registration \> Pregnant, expected (desired or planned) pregnant, or breastfeeding patients
* \< At 1st registration \> Use of prohibited medications or treatment in this study
* \< At 1st registration \> Patients who received investigational product in this study (re-enrollment prohibited)
* \< At 1st registration \> Patients who have received treatment with investigational product other than this study within 4 months prior to informed consent
* \< At 1st registration \> Patients with a history of hypersensitivity to methylprednisolone sodium succinate
* \< At 1st registration \> Patients who have a tumor associated with autoimmune encephalitis and are considered to require resection during the study period.
* \< At 1st registration \> Patients receiving intravenous general anesthetics or sedative hypnotics
* \< At 1st registration \> Patients in coma
* \< At 1st registration \> Ventilated patients
* \< At 1st registration \> Patients who cannot undergo protocol-specified tests/assessments
* \< At 1st registration \> Other patients considered ineligible for the study by the investigator
* \< At 2nd registration \> Positive herpes simplex virus DNA qualitative test in the screening period.
* \< At 2nd registration \> Serum creatinine ≥ 2 times the upper limit of normal during the screening period.
* \< At 2nd registration \> Total protein ≥ 9 g/dL during the screening period.
* \< At 2nd registration \> Patients with hematocrit ≥ 55% during the screening period
* \< At 2nd registration \> Patients who meet any of the exclusion criteria at the time of first registration

Primary outcomes:
measure: Proportion of responders in CASE (Clinical Assessment Scale in Autoimmune Encephalitis)
timeFrame: 4 weeks
Secondary outcomes:
measure: CASE
timeFrame: 1, 2, 3, 4, 6, 8, 12 weeks
measure: mRS
timeFrame: 1, 2, 3, 4, 6, 8, 12 weeks
measure: GCS
timeFrame: 1, 2, 3, 4, 6, 8, 12 weeks
measure: MMSE-J
timeFrame: 4, 8, 12 weeks
measure: FAB
timeFrame: 4, 8, 12 weeks
measure: Disappearance of abnormal EEG findings
timeFrame: 4, 12 weeks
measure: Disappearance of abnormal head MRI findings
timeFrame: 4, 12 weeks
measure: Cerebrospinal fluid test
timeFrame: 4, 12 weeks
measure: Duration of hospitalization
timeFrame: 12 weeks
measure: mRS proportion
timeFrame: 1, 2, 3, 4, 6, 8, 12 weeks
measure: GCS proportion
timeFrame: 1, 2, 3, 4, 6, 8, 12 weeks
Other outcomes:
Locations:
city: Ube
country: Japan
facility: Trial site 1
state: Yamaguchi
Study officials:
affiliation: Nihon Pharmaceutical Co., Ltd
name: Mamoru Ota
role: STUDY_CHAIR
References: