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Trial record 1 of 1 for:    NCT05503264
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A 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 (Cielo)

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ClinicalTrials.gov Identifier: NCT05503264
Recruitment Status : Recruiting
First Posted : August 16, 2022
Last Update Posted : May 10, 2024
Sponsor:
Collaborator:
Chugai Pharmaceutical Co.
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
The purpose of this study is to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab in participants with anti-N-methyl-D-aspartic acid receptor (NMDAR) and anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.

Condition or disease Intervention/treatment Phase
NMDAR Autoimmune Encephalitis LGI1 Autoimmune Encephalitis Drug: Satralizumab Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 27, 2022
Estimated Primary Completion Date : June 23, 2025
Estimated Study Completion Date : December 7, 2027


Arm Intervention/treatment
Experimental: NMDAR autoimmune encephalitis (AIE) cohort
Adults and adolescents with definite or probable NMDAR encephalitis
Drug: Satralizumab

In Part 1, study drug will be administered after all other study related procedures have been performed at a site visit at Weeks 0, 2, 4, and Q4W thereafter. Participants will receive satralizumab according to body weight. Study drug will be administered by SC injection in the abdominal or femoral region after all other study-related procedures have been performed at a site visit.

In Part 2, participants will be asked to choose from one of the following options:

Option 1: continue on randomized, double-blind study drug; Option 2: start open-label satralizumab based on body weight; Option 3: stop study treatment and continue follow-up assessments


Experimental: LGI1 AIE cohort
Adults with LGI1 encephalitis
Drug: Satralizumab

In Part 1, study drug will be administered after all other study related procedures have been performed at a site visit at Weeks 0, 2, 4, and Q4W thereafter. Participants will receive satralizumab according to body weight. Study drug will be administered by SC injection in the abdominal or femoral region after all other study-related procedures have been performed at a site visit.

In Part 2, participants will be asked to choose from one of the following options:

Option 1: continue on randomized, double-blind study drug; Option 2: start open-label satralizumab based on body weight; Option 3: stop study treatment and continue follow-up assessments


Placebo Comparator: NMDAR autoimmune encephalitis (AIE) Placebo cohort
Adults and adolescents with definite or probable NMDAR encephalitis
Other: Placebo
Satralizumab placebo PFS is identical in composition to satralizumab PFS, but does not contain the satralizumab active ingredient and will be identical in appearance and packaging to satralizumab. A PFS (assembled with an NSD and extended finger flange) filled with 0.5 mL of solution, corresponding to 60 mg satralizumab, may be used in Part 2 once it becomes available at the study site.

Placebo Comparator: LGI1 AIE Placebo cohort
Adults with LGI1 encephalitis
Other: Placebo
Satralizumab placebo PFS is identical in composition to satralizumab PFS, but does not contain the satralizumab active ingredient and will be identical in appearance and packaging to satralizumab. A PFS (assembled with an NSD and extended finger flange) filled with 0.5 mL of solution, corresponding to 60 mg satralizumab, may be used in Part 2 once it becomes available at the study site.




Primary Outcome Measures :
  1. Part 1: Proportion of participants with mRS score improvement ≥ 1 from baseline and no use of rescue therapy at Week 24 [ Time Frame: Baseline up to Week 24 ]
    mRS = Modified Rankin Scale

  2. Part 2: Percentage of participants with adverse events [ Time Frame: From Week 52 up to 2 years ]

Secondary Outcome Measures :
  1. Part 1: Time to mRS score improvement ≥ 1 from baseline without use of rescue therapy [ Time Frame: Baseline up to Week 52 ]
    mRS = Modified Rankin Scale

  2. Part 1: Time to rescue therapy [ Time Frame: Baseline up to Week 52 ]
  3. Part 1: Time to seizure freedom or cessation of status epilepticus without use of rescue therapy [ Time Frame: Baseline up to Week 24 ]
    Seizure freedom defined as a cessation of seizures for at least 6 consecutive weeks

  4. Part 1: Change in CASE score from baseline at Week 24 [ Time Frame: Baseline up to Week 24 ]
    CASE = Clinical Assessment Scale in Autoimmune Encephalitis

  5. Part 1: MOCA total score at Week 24 [ Time Frame: Baseline up to Week 24 ]
    MOCA = Montreal Overall Cognitive Assessment;

  6. Part 1: RAVLT score at Week 24 (LGI1 AIE cohort) [ Time Frame: Baseline up to Week 24 ]
    RAVLT = Rey Auditory Verbal Learning Test.

  7. Part 1: mRS score at Week 24 (as measured on a 7-point scale; NMDAR AIE cohort) [ Time Frame: Baseline up to Week 24 ]
    mRS = Modified Rankin Scale

  8. Part 1: Percentage of participants with adverse events [ Time Frame: Baseline, Week 52, 2 Years ]
    Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Reasonable exclusion of tumor or malignancy before baseline visit (randomization)
  • Onset of autoimmune encephalitis (AIE) symptoms <=9 months before randomization
  • Meet the definition of "New Onset" or "Incomplete Responder" AIE
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab or placebo
  • For participants enrolled in the extended China enrollment phase at National Medical Products Administration (NMPA)-recognized sites: participants who are current residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry

N-methyl-D-aspartic acid receptor (NMDAR) AIE Cohort

  • Age >=12 years
  • Diagnosis of probable or definite NMDAR encephalitis

Leucine-rich glioma-inactivated 1 (LGI1) AIE Cohort

  • Age >=18 years
  • Diagnosis of LGI1 encephalitis

Exclusion Criteria:

  • Any untreated teratoma or thymoma at baseline visit (randomization)
  • History of carcinoma or malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for >=5 years before screening
  • For patients with NMDAR AIE, history of negative anti-NMDAR antibody in cerebrospinal fluid (CSF) using a cell-based assay within 9 months of symptom onset
  • Historically known positivity to an intracellular antigen with high cancer association or GAD-65
  • Historically known positivity to any cell surface neuronal antibodies other than NMDAR and LGI1
  • Confirmed paraneoplastic encephalitis
  • Confirmed central or peripheral nervous system demyelinating disease
  • Alternative causes of associated symptoms
  • 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
  • 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
  • Concurrent use of more than one IST as background therapy
  • Contraindication to all of the following rescue treatments: rituximab, IVIG, high-dose corticosteroids, or intravenous (IV) cyclophosphamide
  • Any surgical procedure, except laparoscopic surgery or minor surgeries within 4 weeks prior to baseline, excluding surgery for thymoma or teratoma removal
  • Planned surgical procedure during the study
  • Evidence of progressive multifocal leukoencephalopathy
  • Evidence of serious uncontrolled concomitant diseases that may preclude patient participation
  • Congenital or acquired immunodeficiency, including HIV infection
  • Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection
  • Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to baseline visit
  • Positive hepatitis B (HBV) and hepatitis C (HCV) test at screening
  • Evidence of latent or active tuberculosis (TB)
  • History of drug or alcohol abuse within 1 year prior to baseline
  • History of diverticulitis or concurrent severe gastrointestinal (GI) disorders that, in the investigator's opinion, may lead to increased risk of complications such as GI perforation
  • Receipt of live or live-attenuated vaccine within 6 weeks prior to baseline visit
  • History of blood donation (1 unit or more), plasma donation or platelet donation within 90 days prior to screening
  • History of severe allergic reaction to a biologic agent
  • Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes safe participation in and completion of the study
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of study drug
  • Laboratory abnormalities at Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05503264


Contacts
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Contact: Reference Study ID Number: WN43174, https://forpatients.roche.com/ 888-662-6728 (U.S.) global-roche-genentech-trials@gene.com
Contact: Global Medical Information: global.medical_information@roche.com

Locations
Show Show 74 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical Co.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05503264    
Other Study ID Numbers: WN43174
2021-002395-39 ( EudraCT Number )
First Posted: August 16, 2022    Key Record Dates
Last Update Posted: May 10, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Encephalitis
Autoimmune Diseases of the Nervous System
Epilepsies, Partial
Hashimoto Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroinflammatory Diseases
Autoimmune Diseases
Immune System Diseases
Thyroiditis, Autoimmune
Thyroiditis
Thyroid Diseases
Endocrine System Diseases
Epilepsy