A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER BASKET STUDY TO EVALUATE THE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SATRALIZUMAB IN PATIENTS WITH ANTI*N METHYL D ASPARTIC ACID RECEPTOR (NMDAR) OR ANTI*LEUCINE RICH GLIOMA INACTIVATED 1 (LGI1) ENCEPHALITIS
- Conditions
- BRAIN Inflammation and encephalitis1000381610011305
- Registration Number
- NL-OMON51721
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 6
Zie paraaf 5.1. en 5.2 in het protocol V2
Inclusion Criteria for All Participants
* Capable of giving signed informed consent as described in Appendix 1
* Reasonable exclusion of tumor or malignancy before baseline visit
(randomization)
* Onset of AIE symptoms, < 9 months before randomization
* Meet the definition of New Onset or Incomplete Responder AIE
- Has a stable (for at least 24 hours) mRS score = or > 2, measured at baseline
- Has received their first acute first-line therapy within 6 weeks prior to
randomization (baseline visit)
- Has not received prior treatment with rituximab or any other ISTs
(e.g., cyclophosphamide, mycophenolate mofetil, methotrexate,
cyclosporine, tacrolimus, azathioprine) or tocilizumab for AIE
- Incomplete Responder: defined as a participant with NMDAR or LGI1 AIE who
satisfies the following criteria:
o Has a stable (for at least 24 hours) mRS score = or > 2, measured at baseline
o Has received their first acute first-line therapy more than 6 weeks prior to
randomization (baseline visit).
o Has received immunotherapy beyond their first acute first-line therapy
course.
* For women of childbearing potential: agreement to remain abstinent or use
adequate contraception during the treatment
period and for at least 3 months after the final dose of satralizumab or placebo
Additional Inclusion Criteria for the NMDAR AIE Cohort
In addition to the criteria outlined in Section 5.1.1, participants are
eligible to be included
in the NMDAR AIE cohort only if all of the following criteria apply:
* Age, > 12 years at the time of signing Informed Consent Form
* Signed Assent Form
* Diagnosis of probable or definite NMDAR encephalitis
Additional Inclusion Criteria for the LGI1 AIE Cohort
In addition to the criteria outlined in Section 5.1.1, participants are
eligible to be included
in the LGI1 AIE cohort only if all of the following criteria apply:
* Age, > 18 years at the time of signing Informed Consent Form
* Diagnosis of LGI1 encephalitis
* Any untreated teratoma or thymoma at baseline visit (randomization). Teratoma
or thymoma detected prior to or during the screening period is allowed if
deemed cured after treatment (usually surgical removal) by 1 week prior to
baseline
* History of carcinoma or malignancy, unless deemed cured by adequate treatment
with no evidence of recurrence for = and > 5 years before screening (except
basal cell and
squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri
that
have been completely excised and cured)
* For patients with NMDAR AIE, history of negative anti-NMDAR antibody in CSF
using a cell based assay within 9 months of symptom onset
* Historically known positivity to an intracellular antigen with high cancer
association
(e.g., anti-Hu, anti-Ma2, anti-CRMP5, anti-Yo, anti-amphiphysin, AMPA, mGluR5,
and GABAB) or GAD-65
* Historically known positivity to any cell surface neuronal antibodies other
than
NMDAR and LGI1 (e.g., caspr2, IgLON5, DPPX, GABAA, and neurexin-3a)
* Confirmed paraneoplastic encephalitis
* Confirmed central or peripheral nervous system demyelinating disease (e.g.,
multiple sclerosis, chronic inflammatory demyelinating polyneuropathy)
* Alternative causes of associated symptoms, including CNS infections, septic
encephalopathy, metabolic encephalopathy, epileptic disorders, mitochondrial
disease, Klein-Levin syndrome, Creutzfeldt-Jakob disease, rheumatologic
disorders,
Reyes syndrome, or inborn errors of metabolism
* History of herpes simplex virus encephalitis in the previous 24 weeks
* Any previous/concurrent treatment with IL-6 inhibitory therapy (e.g.,
tocilizumab),
alemtuzumab, total body irradiation, or bone marrow transplantation
* Any previous treatment with anti-CD19 antibody, complement inhibitors,
neonatal Fc
receptor antagonists, anti*B-lymphocyte stimulator monoclonal antibody
(e.g., belimumab)
* Any previous treatment with T-cell depleting therapies, cladribine, or
mitoxantrone
* Treatment with oral cyclophosphamide within 1 year prior to baseline
* Treatment with any investigational drug (including bortezomib) within 24
weeks prior
to screening (or within 5 half-lives of the investigational drug; whichever is
longer)
* Concurrent use of more than one IST (e.g.. azathioprine, mycophenolate
mofetil, or
IV cyclophosphamide) as background therapy
The combination of an OCS with another permitted IST drug is allowed.
* Contraindication to all of the following rescue treatments: rituximab, IVIG,
high-dose
corticosteroids, or IV cyclophosphamide
* Any surgical procedure, except laparoscopic surgery or minor surgeries
(defined as
procedures that require only local anesthesia or conscious sedation, i.e., do
not
require general, neuraxial or regional anesthesia, and are done on an
ambulatory/outpatient basis; e.g. toenail surgery, mole surgical excision,
wisdom
tooth extraction), within 4 weeks prior to baseline, excluding surgery for
thymoma or
teratoma removal
* Planned surgical procedure (except minor surgeries) during the study
* Evidence of progressive multifocal leukoencephalopathy
* Evidence of serious uncontrolled concomitant diseases that may preclude
patient
participation, such as other nervous system disease, cardiovascular disease,
hematologic/hematopoiesis disease,
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the efficacy of satralizumab compared with placebo on degree of<br /><br>disability and clinical severity:<br /><br><br /><br>• Proportion of participants with mRS score improvement = or > 1 from baseline<br /><br>and no use of rescue therapy at Week 24</p><br>
- Secondary Outcome Measures
Name Time Method