Phase III Clinical Study of NPB-01 in Patients With Autoimmune Encephalitis

Sponsor

Nihon Pharmaceutical Co., Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05177939

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Encephalitis	Drug: NPB-01 Drug: NPB-01-ME	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase III Study to Evaluate the Efficacy and Safety of NPB-01 in Patients With Autoimmune Encephalitis Refractory to Steroid Pulse Therapy

Anticipated Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

Oct 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NPB-01 Intravenous immunoglobulin	Drug: NPB-01 NPB-01 will be administered for the treatment of autoimmune encephalitis Other Names: Intravenous immunoglobulin
Active Comparator: NPB-01-ME methylprednisolone sodium succinate	Drug: NPB-01-ME NPB-01-ME will be administered for the treatment of autoimmune encephalitis Other Names: methylprednisolone sodium succinate

Arm

Intervention/Treatment

Experimental: NPB-01

Intravenous immunoglobulin

Drug: NPB-01

NPB-01 will be administered for the treatment of autoimmune encephalitis

Other Names:

Intravenous immunoglobulin

Active Comparator: NPB-01-ME

methylprednisolone sodium succinate

Drug: NPB-01-ME

NPB-01-ME will be administered for the treatment of autoimmune encephalitis

Other Names:

methylprednisolone sodium succinate

Outcome Measures

Primary Outcome Measures

Proportion of responders in CASE (Clinical Assessment Scale in Autoimmune Encephalitis) [4 weeks]
A responder is defined as a patient whose CASE score at Week 4 of the post-treatment follow-up period after treatment with investigational product improved by 40% or more compared to the pre-treatment period.

Secondary Outcome Measures

CASE [1, 2, 3, 4, 6, 8, 12 weeks]
The change in CASE score at each time point after the start of treatment with investigational product compared with that on Day 8 of the pretreatment period will be compared between the arms. Changes in CASE scores divided into three segments (0 -4: excellent, 5 -9: moderate, 10 -27: poor) will also be compared. In addition, the period until CASE score becomes 4 points or less after the start of treatment with investigational product will be checked.
mRS [1, 2, 3, 4, 6, 8, 12 weeks]
Changes in mRS at each time point after the start of investigational product treatment compared with Day 8 of the pretreatment period will be compared between the arms.
GCS [1, 2, 3, 4, 6, 8, 12 weeks]
To compare the change in GCS at each time point after the start of investigational product with that on Day 8 of the pretreatment period between the arms.
MMSE-J [4, 8, 12 weeks]
The change in MMSE-J at each time point after the start of investigational product as compared with Day 8 of the pretreatment period will be compared between the arms.
FAB [4, 8, 12 weeks]
The change in FAB at each time point after the start of investigational product as compared with Day 8 of the pretreatment period will be compared between the arms.
Disappearance of abnormal EEG findings [4, 12 weeks]
The proportion of subjects in whom abnormal findings in EEG disappeared at each time point after the start of investigational product as compared with Day 8 of the pretreatment period will be compared between the arms.
Disappearance of abnormal head MRI findings [4, 12 weeks]
The proportion of subjects in whom abnormal findings in head MRI disappeared at each time point after the start of investigational product as compared with Day 8 of the pretreatment period will be compared between the arms.
Cerebrospinal fluid test [4, 12 weeks]
The proportion of subjects in whom the cell count returned to within the reference range (≤ 5/μl) and the proportion of subjects in whom the protein count returned to within the reference range (15.0 ~ 45.0 mg/dL) at each time point after the start of investigational product treatment as compared with Day 8 of the pretreatment period will be checked.
Duration of hospitalization [12 weeks]
Duration of hospitalization after the start of treatment with investigational product to be compared between the arms.
mRS proportion [1, 2, 3, 4, 6, 8, 12 weeks]
The proportions of subjects with an mRS score of ≤ 2, subjects with an improvement of ≥ 1 point, and subjects with an improvement of ≥ 2 points will also be compared. Also, the time to mRS improvement after the start of treatment with investigational product (≤ 2 points, ≥ 1 point improvement, ≥ 2 points improvement) .
GCS proportion [1, 2, 3, 4, 6, 8, 12 weeks]
Changes in GCS when divided into three segments (15-13: Mild, 12-9: Moderate, 8-3: Severe) will also be compared. In addition, the period until the GCS score reaches 13 or higher after the start of treatment with investigational product will be checked.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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):

Definite diagnostic criteria for autoimmune limbic encephalitis
MRI evidence of demyelination (probable autoimmune encephalitis)
Probabilistic diagnostic criteria for anti-NMDAR encephalitis
Probabilistic diagnostic criteria for Bickerstaff brainstem encephalitis
Probabilistic diagnostic criteria for Hashimoto's encephalopathy
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