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

Primary Purpose

Autoimmune Encephalitis

Status
Recruiting
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
NPB-01
NPB-01-ME
Sponsored by
Nihon Pharmaceutical Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Encephalitis

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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):

    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

Sites / Locations

  • Trial site 1Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

NPB-01

NPB-01-ME

Arm Description

Intravenous immunoglobulin

methylprednisolone sodium succinate

Outcomes

Primary Outcome Measures

Proportion of responders in CASE (Clinical Assessment Scale in Autoimmune Encephalitis)
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
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
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
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
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
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
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
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
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
Duration of hospitalization after the start of treatment with investigational product to be compared between the arms.
mRS proportion
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
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.

Full Information

First Posted
December 3, 2021
Last Updated
November 28, 2022
Sponsor
Nihon Pharmaceutical Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05177939
Brief Title
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

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2022 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nihon Pharmaceutical Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Encephalitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NPB-01
Arm Type
Experimental
Arm Description
Intravenous immunoglobulin
Arm Title
NPB-01-ME
Arm Type
Active Comparator
Arm Description
methylprednisolone sodium succinate
Intervention Type
Drug
Intervention Name(s)
NPB-01
Other Intervention Name(s)
Intravenous immunoglobulin
Intervention Description
NPB-01 will be administered for the treatment of autoimmune encephalitis
Intervention Type
Drug
Intervention Name(s)
NPB-01-ME
Other Intervention Name(s)
methylprednisolone sodium succinate
Intervention Description
NPB-01-ME will be administered for the treatment of autoimmune encephalitis
Primary Outcome Measure Information:
Title
Proportion of responders in CASE (Clinical Assessment Scale in Autoimmune Encephalitis)
Description
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.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
CASE
Description
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.
Time Frame
1, 2, 3, 4, 6, 8, 12 weeks
Title
mRS
Description
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.
Time Frame
1, 2, 3, 4, 6, 8, 12 weeks
Title
GCS
Description
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.
Time Frame
1, 2, 3, 4, 6, 8, 12 weeks
Title
MMSE-J
Description
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.
Time Frame
4, 8, 12 weeks
Title
FAB
Description
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.
Time Frame
4, 8, 12 weeks
Title
Disappearance of abnormal EEG findings
Description
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.
Time Frame
4, 12 weeks
Title
Disappearance of abnormal head MRI findings
Description
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.
Time Frame
4, 12 weeks
Title
Cerebrospinal fluid test
Description
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.
Time Frame
4, 12 weeks
Title
Duration of hospitalization
Description
Duration of hospitalization after the start of treatment with investigational product to be compared between the arms.
Time Frame
12 weeks
Title
mRS proportion
Description
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) .
Time Frame
1, 2, 3, 4, 6, 8, 12 weeks
Title
GCS proportion
Description
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.
Time Frame
1, 2, 3, 4, 6, 8, 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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): 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mamoru Ota
Phone
03-5148-7574
Email
kaihatsu@nihon-pharm.co.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mamoru Ota
Organizational Affiliation
Nihon Pharmaceutical Co., Ltd
Official's Role
Study Chair
Facility Information:
Facility Name
Trial site 1
City
Ube
State/Province
Yamaguchi
Country
Japan
Individual Site Status
Recruiting

12. IPD Sharing Statement

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

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