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

A Multicenter, Single Arm, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD)

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 Overview

• Status: Completed
• Conditions: Neuromyelitis Optica Spectrum Disorder
• Intervention / Treatment: Drug: satralizumab; Drug: azathioprine (AZA); Drug: mycophenolate mofetil (MMF); Drug: oral corticosteroids

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT 'Dr. Georgi Stranski', EAD
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • MS Clinical Trials Group
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Université de Montréal (CHUM)
• Croatia
  • Osijek, Croatia, 31000
    • Clinical Hospital Centre Osijek
• Germany
  • Bochum, Germany, 44791
    • Ruhr Universitat Bochum
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University Hospital
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
• Korea, Republic of
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - PPDS
• Malaysia
  • FED. Territory OF Kuala Lumpur
    • Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia, 50586
      • Hospital Kuala Lumpur
• Poland
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
  • Katowice, Poland, 40-571
    • M.A. - LEK A. M. Maciejowscy SC. Centrum Terapii SM
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie; Klinika Neurologii
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii
  • Warszawa, Poland, 04-749
    • Międzyleski Szpital Specjalistyczny w Warszawie
  • Warszawa, Poland, 02-097
    • Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny; Klinika Neurologii
• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • San Juan MS Center
• Romania
  • Campulung, Romania, 115100
    • SC Clubul Sanatatii SRL
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
• Taiwan
  • North Dist., Taiwan, 40402
    • China Medical University Hospital
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 112
    • Taipei Veterans General Hospital
• Turkey
  • Istanbul, Turkey, 34333
    • Bilim University Medical Faculty Florence Nightingale Hospital
• Ukraine
  • Katerynoslav Governorate
    • Dnipro, Katerynoslav Governorate, Ukraine, 49069
      • Municipal Non-Profit Enterprise City Clinical Hospital #16 of Dnipro City Council
  • Kherson Governorate
    • Odesa, Kherson Governorate, Ukraine, 65006
      • Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council
  • Podolia Governorate
    • Vinnytsia, Podolia Governorate, Ukraine, 21037
      • Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
  • Volhynian Governorate
    • Ternopil, Volhynian Governorate, Ukraine, 46027
      • Communal Nonprofit enterprise Ternopil Regional Clinical Psychoneurological Hospital of TRC
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • National Hospital For Neurology and Neurosurgery
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Research and Wellness
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology Ltd
    • Peoria, Illinois, United States, 64637
      • OSF Saint Francis Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University; UHC-4H
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute PA
  • Ohio
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Hospital For Neuroscience; Jefferson Neurology Associates
  • Texas
    • Dallas, Texas, United States, 75390-0001
      • University of Texas Southwestern Medical Center
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Satralizumab Treatment; Participants will receive satralizumab subcutaneously (SC) every 4 weeks (Q4W)

Drug: satralizumab; 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; Other Names: Enspryng; Drug: azathioprine (AZA); 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); Other Names: non-investigational medicinal product (NIMP); Drug: mycophenolate mofetil (MMF); Participants are permitted to use MMF during the study as background immunosuppressive treatment at a maximum dose of 3000 mg/day; Other Names: NIMP; Drug: oral corticosteroids; Participants are permitted to use oral corticosteroids (prednisolone equivalent) during the study as background immunosuppressive treatment at a maximum dose of 15 mg/day; Other Names: NIMP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline up to 523 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Suicidality Assessed Using Columbia-Suicide Severity Rating Scale (C-SSRS)	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	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.	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	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.	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	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.	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.	First dose of satralizumab in parent studies up to end of study WN42349 (up to 523 weeks)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2021
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antibiotics, Antitubercular; Antitubercular Agents; Mycophenolic Acid; Azathioprine
• Other Study ID Numbers: WN42349; 2020-003413-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No