A Study to Evaluate the Safety and Efficacy of Satralizumab in Participants With Neuromyelitis Optica Spectrum Disorder (NMOSD)

Hoffmann-La Roche119 enrolled

Overview

This multicenter, single-arm, open-label study will evaluate the long-term safety and efficacy of satralizumab in participants with neuromyelitis optica spectrum disorder (NMOSD) who completed open-label extension (OLE) period of studies BN40898 and BN40900. Participants will receive satralizumab as monotherapy or in combination with one of the following background immunosuppressive treatments: azathioprine (AZA), mycophenolate mofetil (MMF), or oral corticosteroids.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

119

Conditions

Neuromyelitis Optica Spectrum Disorder

Interventions

satralizumabDRUG

Satralizumab will be administered by SC injection in the abdominal or femoral region at a dose of 120 mg (fixed dose) Q4W for up to 3 years

azathioprine (AZA)DRUG

Participants are permitted to use AZA during the study as background immunosuppressive treatment at a maximum dose of 3 milligram per kilogram per day (mg/kg/day)

mycophenolate mofetil (MMF)DRUG

Participants are permitted to use MMF during the study as background immunosuppressive treatment at a maximum dose of 3000 mg/day

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants aged less than 18 years at the time of informed consent for Study BN40898 can continue treatment with a combination of oral corticosteroids and either AZA or MMF * Participated in Study BN40898 or Study BN40900 with satralizumab in NMOSD, are on ongoing satralizumab treatment and were anti-aquaporin-4 IgG antibody (AQP4-IgG) seropositive at screening in these studies. Participants with NMOSD who were AQP4-IgG seronegative at screening in Study BN40898 or Study BN40900 can be enrolled if the investigator considers the continued treatment with satralizumab to be beneficial for the participant * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 3 months after the final dose of satralizumab. Exclusion Criteria: * Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of study drug. Women of childbearing potential must have a negative urine pregnancy test result on the baseline visit prior to initiation of study drug * Evidence of any serious uncontrolled concomitant diseases that may preclude participation including nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency * Known active infection that requires delaying the next satralizumab dose at the time of enrollment * NMOSD relapse at the time of enrollment * Laboratory abnormalities at the last assessment in Study BN40898 or Study BN40900 that preclude re-treatment with satralizumab

Locations (53)

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE=any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with it. AE can therefore be any unfavorable \& unintended sign, symptoms/disease temporally associated with use of a medicinal (investigational) product, whether or not considered related to it. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention. The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT02073279) was considered as baseline for this outcome measure. All AEs from the time of randomization in the parent studies for satralizumab-treated participants are reported here.

Time frame: Baseline up to 523 weeks

Number of Participants With Adverse Events of Special Interest (AESIs) and Selected AEs

An AESIs included potential drug induced liver injury and suspected transmission of an infectious agent by study drug defined as any organism, virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform encephalopathy), pathogenic or non-pathogenic causing clinical symptoms or laboratory findings that indicate an infection in a participant exposed to a medicinal product. Selected AEs included infections that required treatments with IV antibiotics, antifungals, or antivirals; opportunistic infections that required treatment with oral antibiotics, antifungals, or antivirals and injection related reaction. The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT02073279) was considered as baseline for this outcome measure. All AEs from the time of randomization in the parent studies for satralizumab-treated participants are reported here.

Time frame: Baseline up to 523 weeks

Secondary Outcomes

Number of Participants With Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)

Data from ClinicalTrials.gov

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Participants are permitted to use oral corticosteroids (prednisolone equivalent) during the study as background immunosuppressive treatment at a maximum dose of 15 mg/day

Children's Hospital of Alabama

Birmingham, Alabama, United States

University of Miami

Miami, Florida, United States

Columbus Research and Wellness

Columbus, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Consultants in Neurology Ltd

Northbrook, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Wayne State University; UHC-4H

Detroit, Michigan, United States

The Neurological Institute PA

Charlotte, North Carolina, United States

OhioHealth Research Institute

Columbus, Ohio, United States

...and 43 more locations

C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& include a-Wish to be Dead; b-Non-specific Active Suicidal Thoughts; c-Active Suicidal Ideation with Any Methods(Not Plan) without Intent to Act; d-Active Suicidal Ideation with Some Intent to Act, without Specific Plan; e-Active Suicidal Ideation with Specific Plan \& Intent, f-Preparatory Acts \& Behavior; g-Aborted Attempt; h-Interrupted Attempt; i-Actual Attempt(non-fatal); j-Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.

Time frame: Baseline up to 523 weeks

Number of Participants With Serious Infections and Hepatotoxicity

Hepatotoxicity was defined using the following Medical Dictionary for Regulatory Activities Standardised MedDRA Queries (MedDRA SMQs) - Cholestasis and jaundice of hepatic origin (SMQ narrow) and Drug related hepatic disorders - severe events only (SMQ narrow). The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT02073279 ) was considered as baseline for this outcome measure. Data for all serious infections and hepatotoxicity from the time of randomization in the parent studies for satralizumab-treated participants are reported here.

Time frame: Baseline up to 523 weeks

Time to First Protocol-defined Relapse (PDR) as Assessed by Investigator (iPDR)

Time to first relapse (TFR) was defined as the time from randomization in parent studies to the first occurrence of the first iPDR. PDR=occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or NMOSD. New or worsening neurological symptoms that occur \< 31 days following onset of PDR were considered part of same relapse. The time point of relapse onset=time at which the participant experienced any new or worsening neurological symptoms representing NMOSD clinical relapse(s). For participants who did not relapse at the time of analysis, TFR was censored at the clinical cutoff date (CCOD) or at the time of withdrawal from study. The first dosing visit in current study or randomization visit in the parent studies (NCT02028884/NCT02073279) was considered as baseline. All TFR data from the time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline up to 528 weeks

iPDR-free Rate up to Week 456

iPDR free rate was defined as the percentage of participants who did not experience a protocol-defined relapse as assessed by the investigator. Protocol-defined 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 PDR were considered part of the same relapse. The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT0207327) was considered as baseline for this outcome measure. All data from the time of randomization in the parent studies up to Week 456 for satralizumab-treated participants are reported here. Percentages have been rounded off to the nearest decimal point. Kaplan-Meier method was used to estimate the iPDR-free rates.

Time frame: Baseline up to Week 456

Percentage of Relapse-Free Participants

Protocol-defined 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 PDR were considered part of the same relapse. The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT0207327) was considered as baseline for this outcome measure. All data from the time of randomization in the parent studies up to end of study WN42349 for satralizumab-treated participants are reported here. Participants who did not experience any relapse events are reported here. Percentages have been rounded off to the nearest decimal point.

Time frame: Baseline up to 528 weeks

Annualized Relapse Rate (ARR)

ARR was calculated as total number of relapses experienced divided by the participant-years of the whole study period. Adjusted ARR was calculated using Poisson regression model adjusted by study identifier (BN40898, BN40900). ARR was assessed from randomization in parent studies to the first occurrence of the iPDR. PDR=occurrence of new/worsening neurological symptoms attributable to NMO/NMOSD. New or worsening neurological symptoms that occur \< 31 days following onset of a PDR were considered part of the same relapse. Time point of relapse onset=the time at which the participant experienced any new or worsening neurological symptoms representing NMOSD clinical relapse(s). First dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT02073279) was considered as baseline for this outcome measure. All ARR data from time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline up to 528 weeks

Change 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. Values from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores represent increased disability. Baseline is the last observation on or before the day of first study drug administration in the current study or the parent studies (NCT02028884/NCT02073279). All EDSS data from the time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline and every 24 weeks (up to 528 weeks)

Time to First EDSS Scores Worsening

EDSS=quantitative measure of disability \& for assessment of severity of relapse for participants with NMOSD. Values from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores=increased disability. EDSS worsening=(a) worsening of 2/more points in EDSS score for participants with a baseline score (BS) of 0, (b) worsening of 1/more points in EDSS score for participants with a BS of 1 to 5, or (c) worsening of 0.5 points/more in EDSS score for participants with a BS of 5.5/more. Participants were censored at date of last EDSS assessment or if no EDSS assessment was performed at randomization date. Baseline=last observation on/before day of first study drug administration in current study/parent studies (NCT02028884/NCT02073279). All EDSS data from time of randomization in parent studies up to end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline up to 528 weeks

Event-free Rate for EDSS Score Worsening up to Week 456

Event-free rate for EDSS score worsening was defined as the percentage of participants who did not experience worsening in their EDSS score from baseline. EDSS=quantitative measure of disability \& for assessment of severity of relapse for participants with NMOSD. Values from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores=increased disability. Participants were censored at the date of the last EDSS assessment or if no EDSS assessment was performed at the randomization date. Baseline is defined as the last observation on/before the day of the first study drug administration in current study/parent studies (NCT02028884/NCT02073279). All EDSS data from the time of randomization in the parent studies up to Week 456 for satralizumab-treated participants are reported here. Kaplan-Meier method was used to estimate the event-free rates.

Time frame: Baseline up to Week 456

Percentage of Participants Without EDSS Worsening

EDSS=quantitative measure of disability \& for assessment of severity of relapse for participants with NMOSD. Values from 0 points (normal neurological examination) up to 10 points (death), increasing in increments of 0.5 points. Higher scores=increased disability. EDSS worsening=(a) worsening of 2/more points in EDSS score for participants with a BS of 0, (b) worsening of 1/more points in EDSS score for participants with a BS of 1 to 5, or (c) worsening of 0.5 points/more in EDSS score for participants with a BS of 5.5/more. Baseline=last observation on/before day of first study drug administration in current study/parent studies (NCT02028884/NCT02073279). All EDSS data from time of randomization in parent studies up to end of study WN42349 for satralizumab-treated participants are reported here. Participants who did not experience any EDDS worsening events are reported here. Percentages have been rounded off to the nearest decimal point.

Time frame: Baseline up to 528 weeks

Change in Visual Acuity (VA) Assessed by a Snellen 20-Foot Wall Chart

Visual acuity is measured using Snellen 20-foot wall chart and then converted to logMAR visual acuity scoring. Lower values indicate better visual acuity. Data are reported for right eye (OD) and left eye (OS). Visual acuity scores (Snellen chart) worse than 20/200 \[i.e. CF (counting fingers), HM (hand movement), LP (light perception), or NLP (no LP)\] are converted to logMAR 1.85, logMAR 2.00, logMAR 2.70, and logMAR 3.00 respectively. LogMAR \>= 1 is equivalent to Physically blind. A negative change from baseline indicates an improvement. The first dosing visit in the current study or randomization visit in the parent studies (NCT02028884/NCT02073279) was considered as baseline for this outcome measure. All VA data from the time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline and every 24 weeks (up to 528 weeks)

Concentrations of Interleukin-6 (IL-6) in Blood

Baseline was defined as last observation collected on or before day of first study drug administration in parent studies (NCT02028884/NCT02073279). All data from the time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: Baseline, every two weeks from Weeks 2 to 8; every 4 weeks from Weeks 12 to 192; every 24 weeks from Weeks 216 to 528

Concentrations of Soluble IL-6 Receptor (sIL-6R) in Blood

Time frame: Baseline, every two weeks from Weeks 2 to 8; every 4 weeks from Weeks 12 to 192; every 24 weeks from Weeks 216 to 528

Concentration of C-Reactive Protein (CRP) in Blood

Time frame: Baseline, every two weeks from Weeks 2 to 8; every 4 weeks from Weeks 12 to 192; every 24 weeks from Weeks 216 to 528

Serum Concentration of Satralizumab at Specified Timepoints

Time frame: Baseline, Week 2, Week 4, Week 5, Week 6; every 4 weeks from Weeks 8 to 192; every 24 weeks from Weeks 216 to 528

Number of Participants With Anti-Drug Antibodies (ADAs) From the First Dose of Satralizumab in Studies NCT02028884 or NCT02073279

The number and percentage of ADA-positive participants and ADA-negative participants at baseline (baseline prevalence) and after drug administration (post-baseline incidence) were summarized. Baseline evaluable participants were participants with an ADA assay result at baseline. Post-baseline evaluable participants were participants with an ADA assay from at least one post-baseline sample. Participants positive for ADA= number of participants with positive ADA result. Participants negative for ADA=number of participants with negative or missing baseline ADA result(s) and all negative post-baseline results. Baseline was defined as last observation collected on or before day of first study drug administration in parent studies. All data from the time of randomization in the parent studies up to the end of study WN42349 for satralizumab-treated participants are reported here.

Time frame: First dose of satralizumab in parent studies up to end of study WN42349 (up to 523 weeks)