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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Encephalitis
• Intervention / Treatment: Drug: NPB-01; Drug: NPB-01-ME

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mamoru Ota; Phone Number: 03-5148-7574; Email: kaihatsu@nihon-pharm.co.jp

Study Locations

• Japan
  • Yamaguchi
    • Ube, Yamaguchi, Japan
      • Recruiting
      • Trial site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1, 2, 3, 4, 6, 8, 12 weeks
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.	1, 2, 3, 4, 6, 8, 12 weeks
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.	1, 2, 3, 4, 6, 8, 12 weeks
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.	4, 8, 12 weeks
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.	4, 8, 12 weeks
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.	4, 12 weeks
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.	4, 12 weeks
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.	4, 12 weeks
Duration of hospitalization	Duration of hospitalization after the start of treatment with investigational product to be compared between the arms.	12 weeks
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) .	1, 2, 3, 4, 6, 8, 12 weeks
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.	1, 2, 3, 4, 6, 8, 12 weeks

Collaborators and Investigators

• Sponsor: Nihon Pharmaceutical Co., Ltd
• Investigators: Study Chair: Mamoru Ota, Nihon Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Thyroid Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Hashimoto Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: NPB-01-19/C-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No