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

• ClinicalTrials.gov Identifier: NCT05269667
• Recruitment Status: Recruiting
• First Posted: March 8, 2022
• Last Update Posted: March 3, 2023
• Sponsor: Hoffmann-La Roche
• Collaborator: Chugai Pharmaceutical Co.
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: February 15, 2022
• First Posted Date: March 8, 2022
• Last Update Posted Date: March 3, 2023
• Actual Study Start Date: August 2, 2022
• Estimated Primary Completion Date: May 29, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2022)

• Proportion of relapse-free patients [ Time Frame: Up to Week 96 ]
• Annualized relapse rate (ARR) [ Time Frame: Up to Week 96 ]
• Time to first relapse (TFR) [ Time Frame: Up to Week 96 ]
• Mean change from baseline in Expanded Disability Status Scale (EDSS) score over the course of the study [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
  The Expanded Disability Status Scale ranges from 0 to 10 in 0.5 unit increments. Higher results represent higher levels of disability.
• Time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks and 24 weeks [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
• Change from baseline in the Symbol Digital Modalities Test (SDMT) over the course of the study [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
• Change in high-contrast (100%) and lowcontrast (2.5%) visual acuity using appropriate high-and low-contrast letter acuity (LCLA) charts over the course of the study [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
• Proportion of participants hospitalized due to relapse [ Time Frame: Up to Week 96 ]
• Proportion of participants using corticosteroids due to relapse [ Time Frame: Up to Week 96 ]
• Proportion of participants in need of rescue therapy due to relapse [ Time Frame: Up to Week 96 ]
• Proportion of participants in need of plasma exchange due to relapse [ Time Frame: Up to Week 96 ]
• Proportion of participants with disability (measured by Expanded Disability Status Scale EDSS) due to relapse [ Time Frame: Up to Week 96 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 25, 2022)

• Count, volume and regional distribution of T2-weighted fluid-attenuated inversion-recovery (FLAIR) hyperintense lesions [ Time Frame: Up to Week 96 ]
  Including new and enlarging lesions of the cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum; Fazekas scoring
• Global and regional brain volume loss including basal ganglia, cerebellum and upper cervical spinal cord. [ Time Frame: At Screening, Weeks 48 and 96 ]
• New and persisting short T1 inversion recovery (STIR)/Proton Density (PD) hyperintense lesions and T1-weighted contrast enhancement [ Time Frame: Up to Week 96 ]
• Quantitative T1 mapping (magnetizationprepared rapid gradient echo sequence [MP2RAGE]) [ Time Frame: Up to Week 96 ]
• Quantitative diffusion/diffusion tensor imaging (DTI) [ Time Frame: Up to Week 96 ]
• Change in the retinal nerve fiber layer (RNFL) thickness [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
• Change in the ganglion cell plus inner plexiform (GCIP) layer thickness [ Time Frame: Baseline (Day -28 to Day -1) to Week 96 ]
• Incidence and severity of adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs) [ Time Frame: Up to Week 96 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention
• Official Title: SAkuraBonsai: Clinical, Imaging And Biomarker Open-Label Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention
• 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).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Neuromyelitis Optica Spectrum Disorder
• NMOSD

Intervention

Drug: 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).

Study Arms

• Experimental: 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).
  Intervention: Drug: Satralizumab 120 mg
• Experimental: 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).
  Intervention: Drug: Satralizumab 120 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 25, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 15, 2027
• Estimated Primary Completion Date: May 29, 2026 (Final data collection date for primary outcome measure)

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 Exclusion criteria for both the cohorts

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: MN42928, https://forpatients.roche.com/; 888-662-6728 (U.S.); global-roche-genentech-trials@gene.com

• Listed Location Countries: France, Italy, Japan, Korea, Republic of, Turkey, United States
• Removed Location Countries: Canada, Germany, India

Administrative Information

• NCT Number: NCT05269667
• Other Study ID Numbers: MN42928; 2021-001088-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Chugai Pharmaceutical Co.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: March 2023