A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention

NCT ID: NCT05269667

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-02
• Study Completion Date: 2023-10-26

Brief Summary

Objective of the trial is to describe the efficacy and safety of satralizumab in patients with aquaporin-4 (AQP4) antibody seropositive NMOSD, either treatment naive or inadequate responders to previous treatment with rituximab (RTX) (or its biosimilar)

Detailed Description

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are severe demyelinating inflammatory autoimmune neurological disorders. The estimated global pooled prevalence of NMOSD is 1.82 per 100 000 people (Etemadifar et al. 2015). The disorder is characterized by inflammatory lesions in the optic nerve, spinal cord, brainstem, and cerebrum; and clinically by optic neuritis (ON) and/or transverse myelitis causing potentially severe motor and sensory impairment, bladder dysfunction, vision loss, pain, and other debilitating symptoms (Wingerchuk et al. 2015). Recovery is variable, and inflammatory attacks often result in permanent disability. Untreated, the risks of severe disability or death are substantial (Jarius et al. 2014).

NMOSD is radiologically and prognostically distinct from multiple sclerosis (MS), and has a pathophysiology unresponsive to typical MS treatment (Weinshenker 2007; Oh, and Levy et al. 2012).

Conditions

Neuromyelitis Optica Spectrum Disorder; NMOSD

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: treatment-naïve NMOSD patients

Patients will be treated with 120 mg satralizumab subcutaneously (SC) as monotherapy at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Week 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. All assessments (clinical, laboratory and imaging) should be performed before satralizumab administration. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).

Group Type: EXPERIMENTAL

Satralizumab 120 mg

Intervention Type: DRUG

Satralizumab 120 mg will be administered as monotherapy (SC) in the abdominal or femoral region at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Weeks 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).

Cohort 2: NMOSD patients who are inadequate responders to previous treatment with RTX

Patients will be treated with 120 mg satralizumab subcutaneously (SC) as monotherapy at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Week 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. All assessments (clinical, laboratory and imaging) should be performed before satralizumab administration. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).

Group Type: EXPERIMENTAL

Satralizumab 120 mg

Intervention Type: DRUG

Satralizumab 120 mg will be administered as monotherapy (SC) in the abdominal or femoral region at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Weeks 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).

Interventions

Satralizumab 120 mg

Satralizumab 120 mg will be administered as monotherapy (SC) in the abdominal or femoral region at Weeks 0, 2 (±3 days), 4 (±3 days), and then every 4 weeks (±3 days) till the last administration at Week 92 followed by a clinical evaluation at Week 96. The first dose at Weeks 0 (baseline visit) will be administered at the study site by the designated site staff during the scheduled study visit. The next dose at Week 2 will be self-administered by the patient under the supervision of a designated study staff at the study site. All the subsequent doses will be self-administered by the patient following training from a healthcare provider (for patients who are not able to administer satralizumab SC by themselves, support by a caregiver/nurse is advised).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 to 74 years, inclusive, at the time of informed consent
• Have a diagnosis of AQP4 antibody seropositive NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria
• For women of childbearing potential: agreement to either remain abstinent (refrain from heterosexual intercourse) or to use reliable means of contraception (physical barrier [patient or partner] in conjunction with a spermicidal product, contraceptive pill, patch, injectables, intrauterine device or intrauterine system) during the treatment period and for at least 3 months after the last dose of study drug Cohort 1 (treatment-naïve NMOSD patients)
• Confirmation of NMOSD diagnosis with AQP4+ antibodies
• Have clinical evidence of at least 1 documented attack or relapse (including first attack) in the last year prior to screening
• Naive to maintenance therapy (disease-modifying therapy [DMT] or immunosuppressive therapy [IST]) Cohort 2 (NMOSD patients with inadequate response to RTX [or its biosimilar])
• Confirmation of NMOSD diagnosis and AQP4+ antibodies in the disease history of the patient
• Have a length of disease duration from first symptom of ≤5 years
• History of ongoing treatment with RTX (or its biosimilar) (at least 2 infusions) for NMOSD with a maximum duration of 6 months since last administration prior to enrolment in the study
• Ongoing disease activity after last RTX (or its biosimilar) infusion i.e., relapse and/or any new inflammatory event, confirmed by magnetic resonance imaging (MRI) or ophthalmological assessment

Exclusion Criteria

• Inability to complete an MRI
• Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of satralizumab
• Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
• Evidence of other demyelinating disease, including MS or progressive multifocal leukoencephalopathy (PML)
• Evidence of serious uncontrolled concomitant diseases that may preclude patient participation
• Active or presence of recurrent bacterial, viral, fungal, mycobacterial infection or other infection (excluding fungal infections of nail beds or caries dentium) at baseline
• Infection requiring hospitalization or treatment with intravenous (IV) anti-infective agents within 4 weeks prior to baseline visit
• Evidence of chronic active hepatitis B
• Evidence of active tuberculosis (TB)
• History or laboratory evidence of coagulation disorders
• Receipt of a live or live-attenuated vaccine within 6 weeks prior to baseline
• Presence or history of malignancy
• History of drug or alcohol abuse within 1 year prior to baseline
• History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation
• 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
• Treatment with any investigational agent within 6 months prior to baseline or 5 drug elimination half-lives of the investigational agent (whichever is longer) Cohort 1 (treatment-naïve NMOSD patients)
• Any previous treatment with IL-6 inhibitory therapy (e.g., tocilizumab), alemtuzumab, total body irradiation, stem-cell therapy, or bone marrow transplantation
• Any previous treatment with eculizumab, belimumab, natalizumab, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, siponimod, or ozanimod
• Any previous treatment with anti-CD4, cladribine or mitoxantrone
• Any previous treatment with B-cell depleting agents
• Any previous treatment with immunosuppressants Cohort 2 (NMOSD patients with inadequate response to RTX)
• Discontinued RTX (or biosimilar) treatment due to any other reason than inadequate response to treatment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chugai Pharmaceutical Co.

UNKNOWN

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

National Cancer Center

Goyang-si, , South Korea

Ondokuz Mayis University School of Medicine

Samsun, , Turkey (Türkiye)

Countries

United States; South Korea; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021-001088-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MN42928

Identifier Type: -

Identifier Source: org_study_id