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

NCT05269667 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: MN429282021-001088-26
• Study Type: interventional
• Target: 4
• Locations: 3 countries
• Sites: 3

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)

Conditions

Neuromyelitis Optica Spectrum Disorder; NMOSD

Outcome Measures

Primary Outcomes (14)

• Percentage of Relapse-Free Participants

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.

  Up to 14 months

• Annualized Relapse Rate (ARR)

  The ARR was calculated descriptively by dividing the total number of relapses for all participants by the total years of drug exposure. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.

  Up to 14 months

• Time to First Relapse (TFR)

  TFR was defined as the time from first dose of satralizumab to the first occurrence of relapse. Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.

  Up to 14 months

• Percentage of Participants Hospitalized Due to Relapse

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the occurrence of hospitalization.

  Up to 14 months

• Percentage of Participants Using Corticosteroids Due to Relapse

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on use of corticosteroids.

  Up to 14 months

• Percentage of Participants in Need of Rescue Therapy Due to Relapse

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need of rescue therapy. Rescue therapy for clinical relapse included pulse intravenous (IV) corticosteroids, oral corticosteroids for tapering, intravenous immunoglobulin (IVIG) and/or apheresis (including plasma exchange and plasmapheresis).

  Up to 14 months

• Percentage of Participants in Need of Plasma Exchange Due to Relapse

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse. The severity of relapses was assessed based on the need for plasma exchange.

  Up to 14 months

• Percentage of Participants With Residual Disability Due to Relapse

  Relapse was the occurrence of new or worsening neurological symptoms attributable to NMOSD. New or worsening neurological symptoms that occur \<31 days following the onset of a relapse were considered part of the same relapse.

  Up to 14 months

• Change From Baseline in Expanded Disability Status Scale (EDSS) Score

  EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. A negative change from baseline indicates improvement.

  Up to Week 36

• Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks

  EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening.

  Up to 12 weeks

• Change From Baseline in the Symbol Digital Modalities Test (SDMT)

  SDMT testing was to detect impairment of key neurocognitive functions that underlie many substitution tasks, including sustained attention, visual scanning, and recent memory. The test consisted of a sequence of 110 symbols displayed in a maximum 90 seconds and a reference key legend with 9 symbols in a given order and their respective matching digits from 1 to 9. The test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement.

  Baseline, Week 24

• Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts

  Best corrected high-contrast (100%) and low-contrast (2.5%) visual acuities were measured at distances of both 4 and 1 meters with the appropriate eye charts. Each eye was tested individually. No visual acuities were obtained with both eyes open. The participants read the charts from left to right starting with the top line (largest letters). The participants proceeded to each lower line until he/she could not see the letters. The total number of letters read correctly were recorded for each eye. Visual acuity was measured before any drops are instilled into the eye and before OCT assessments.

  Baseline and Week 24

• Change in Visual Functioning Questionnaire -25 (VFQ-25)

  The National Eye institute (NEI) VFQ-25 captures a participants's perception of vision-related functioning and vision-related quality of life. The core measures include 25 items that comprise 11 vision-related subscales and one item on general health. The NEI VFQ-25 also included an appendix of additional items that was used to expand the scales up to 39 total items. The composite score and the subscale scores range from 0 to 100, with higher scores indicating better vision-related functioning.

  At Week 24

• Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks

  EDSS was a quantitative measure of disability and for assessment of severity of relapse for participants with NMOSD. The overall score ranges from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. CDP was defined as 1-point or greater worsening in EDSS from baseline that is not attributable to another etiology when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. Disability progression was considered confirmed when the increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening.

  Up to 24 weeks

Secondary Outcomes (14)

• Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans

  Weeks 4, 8, 12 and 24

• Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans

  Baseline, Week 12

• Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans

  Basline, Weeks 4, and 12

• Number of Participants With Diffusion Abnormalities, Microbleeds and Cerebral Perfusion Alterations Assessed Using MRI Scans

  Up to 14 Months

• Number of Participants With Global and Regional Brain Volume Loss Assessed Using MRI Scans

  Up to 14 Months

Study Arms (2)

Cohort 1: treatment-naïve NMOSD patients

EXPERIMENTAL

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).

Drug: Satralizumab 120 mg

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

EXPERIMENTAL

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).

Drug: Satralizumab 120 mg

Interventions

Satralizumab 120 mg 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 1: treatment-naïve NMOSD patients; Cohort 2: NMOSD patients who are inadequate responders to previous treatment with RTX

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical Co.: collaborator

Study Sites (3)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Ondokuz Mayis University School of Medicine

Samsun, 55239, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

satralizumab

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 8, 2022
• Study Start: August 2, 2022
• Primary Completion: October 26, 2023
• Study Completion: October 26, 2023
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

TU (1); US (1); KR (1)