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

Autoimmune Encephalitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05177939
• Other study ID #: NPB-01-19/C-01
• Status: Recruiting
• Phase: Phase 3
• Start date: March 3, 2022
• Est. completion date: October 31, 2024

Study information

• Verified date: January 2022
• Source: Nihon Pharmaceutical Co., Ltd
• Contact: Mamoru Ota
• Phone: 03-5148-7574
• Email: kaihatsu[@]nihon-pharm.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Encephalitis
• Encephalitis
• Hashimoto Disease

Intervention

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

Locations

Country	Name	City	State
Japan	Trial site 1	Ube	Yamaguchi

Sponsors (1)

Lead Sponsor	Collaborator
Nihon Pharmaceutical Co., Ltd

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of hospitalization	Duration of hospitalization after the start of treatment with investigational product to be compared between the arms.	12 weeks
Secondary	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
Secondary	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