A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention
- Conditions
- Neuromyelitis Optica Spectrum DisorderNMOSD
- Interventions
- Registration Number
- NCT05269667
- Lead Sponsor
- Hoffmann-La Roche
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: treatment-naïve NMOSD patients Satralizumab 120 mg 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). Cohort 2: NMOSD patients who are inadequate responders to previous treatment with RTX Satralizumab 120 mg 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).
- Primary Outcome Measures
Name Time Method Percentage of Relapse-Free Participants Up to 14 months 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.
Annualized Relapse Rate (ARR) Up to 14 months 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.
Time to First Relapse (TFR) Up to 14 months 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.
Percentage of Participants Hospitalized Due to Relapse Up to 14 months 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.
Percentage of Participants Using Corticosteroids Due to Relapse Up to 14 months 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.
Percentage of Participants in Need of Rescue Therapy Due to Relapse Up to 14 months 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).
Percentage of Participants in Need of Plasma Exchange Due to Relapse Up to 14 months 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.
Percentage of Participants With Residual Disability Due to Relapse Up to 14 months 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.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Up to Week 36 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.
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 12 Weeks Up to 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.
Change From Baseline in the Symbol Digital Modalities Test (SDMT) Baseline, Week 24 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.
Change in High Contrast (100%) and Low Contrast (2.5%) Visual Acuity Using High-and Low-contrast Letter Acuity (LCLA) Charts Baseline and Week 24 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.
Change in Visual Functioning Questionnaire -25 (VFQ-25) At Week 24 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.
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks Up to 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.
- Secondary Outcome Measures
Name Time Method Quantitative Diffusion/ Diffusion Tensor Imaging (DTI) Assessed Using MRI Scans Up to 14 months Change in the Retinal Nerve Fiber Layer (RNFL) Thickness Assessed Using Optical Coherence Tomography (OCT) Up to 14 months Change in the Ganglion Cell Plus Inner Plexiform (GCIP) Layer Thickness Assessed Using OCT Up to 14 months Concentration of Satralizumab in Cerebrospinal Fluid (CSF) and Serum Baseline and Week 12 Number of Participants With Anti-satralizumab Antibodies Up to 14 months Count of T2-weighted Fluid-Attenuated Inversion-Recovery (FLAIR) Hyperintense Lesions Assessed Using Magnetic Resonance Imaging (MRI) Scans Weeks 4, 8, 12 and 24 MRI was used to monitor central nervous system (CNS) lesions and potentially other pathophysiology, such as inflammation and neurodegeneration. LETM=longitudinally extensive transverse myelitis. Stm=subcortical temporal medial. Count of T2-weighted FLAIR hyperintense lesions (including new and enlarging) were distributed across the following regions: cerebrum, optic nerves, optic chiasm, area postrema, brainstem and cerebellum.
Volume of T2-weighted FLAIR Hyperintense Lesions Assessed Using MRI Scans Baseline, Week 12 MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration.
Number of Participants With Contrast-enhancing T1-weighted Lesions (CEL) Assessed Using MRI Scans Basline, Weeks 4, and 12 MRI was used to monitor CNS lesions and potentially other pathophysiology, such as inflammation and neurodegeneration.
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 Number of Participants With New and Persisting Short T1 Inversion Recovery (STIR)/ Proton Density (PD) Hyperintense Lesions and T1-weighted Contrast Enhancement Assessed Using MRI Scans Up to 14 months Quantitative T1 Mapping (Magnetization Prepared Rapid Gradient Echo Sequence [MP2RAGE]) Assessed Using MRI Scans Up to 14 months T2*/R* Ratio for Iron Concentration Estimation Assessed Using MRI Scans Up to 14 months Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) Up to 14 months An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. An AESI included drug induced liver injury and suspected transmission of infectious agent via medicinal products.
Trial Locations
- Locations (3)
Ondokuz Mayis University School of Medicine
🇹🇷Samsun, Turkey
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of