Trial Outcomes & Findings for N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders (NCT NCT02200770)

NCT ID: NCT02200770

Last Updated: 2021-12-03

Results Overview

The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

231 participants

Primary outcome timeframe

Day 1 (Baseline) through Day 197

Results posted on

2021-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo/Inebilizumab Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Randomized-controlled Period (RCP) STARTED	56	175
Randomized-controlled Period (RCP) Treated	56	174
Randomized-controlled Period (RCP) COMPLETED	54	169
Randomized-controlled Period (RCP) NOT COMPLETED	2	6
Open-label Period (OLP) STARTED	51	165
Open-label Period (OLP) COMPLETED	43	131
Open-label Period (OLP) NOT COMPLETED	8	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Inebilizumab Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Randomized-controlled Period (RCP) Adverse Event	0	2
Randomized-controlled Period (RCP) Withdrawal by Subject	1	1
Randomized-controlled Period (RCP) Participants randomized, but not treated	0	1
Randomized-controlled Period (RCP) Other	1	2
Open-label Period (OLP) Adverse Event	1	2
Open-label Period (OLP) Death	1	2
Open-label Period (OLP) Lost to Follow-up	0	1
Open-label Period (OLP) Withdrawal by Subject	0	14
Open-label Period (OLP) Other	6	15

Baseline Characteristics

N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Total n=230 Participants Total of all reporting groups
Age, Continuous	42.6 Years STANDARD_DEVIATION 13.9 • n=5 Participants	43.0 Years STANDARD_DEVIATION 11.6 • n=7 Participants	42.9 Years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	159 Participants n=7 Participants	209 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	15 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	28 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	146 Participants n=7 Participants	187 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	39 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	15 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	92 Participants n=7 Participants	120 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Time to Adjudication Committee (AC)-Determined Neuromyelitis Optica Spectrum Disorder (NMOSD) Attack During RCP	NA Days Interval 142.0 to Median and upper level of 95% Confidence Interval (CI) are not reported as there were insufficient events to determine the median.	NA Days Median and 95% CI are not reported as there were insufficient events to determine the median.

SECONDARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment.

EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP	33.9 Percentage of Participants	14.9 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with low contrast visual acuity binocular score were analyzed for this outcome measure.

Low-contrast visual acuity test is used to determine the number of letters that can be read on a standardized low-contrast Landolt C Broken Rings Chart held at a distance of 3 meters. Binocular score is the number of letters read correctly on an eye chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=171 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP	1.442 Score on scale Standard Error 1.217	1.576 Score on scale Standard Error 0.935

SECONDARY outcome

Timeframe: From Screening (Day -28) to Day 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with observed MRI lesions were analyzed for this outcome measure.

The number of new gadolinium-enhancing lesions and new or enlarging T2 lesions were measured by MRI of the brain, optic nerve, and spinal cord.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=32 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=79 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP	2.3 Number of lesions Standard Deviation 1.3	1.6 Number of lesions Standard Deviation 1.0

SECONDARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. Participants with in-patient hospitalization were analyzed for this outcome measure.

Participants with relapsing NMOSD have recurrent attacks that can be severe and result in blindness, paralysis, and even death and consequently, such attacks frequently result in in-patient hospitalizations. In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=8 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=11 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of NMOSD-related In-patient Hospitalizations During RCP	1.4 Number of In-patient Hospitalizations Standard Deviation 0.7	1.0 Number of In-patient Hospitalizations Standard Deviation 0

SECONDARY outcome

Timeframe: For participants randomized to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomized to placebo: Day 1 of OLP through the end of OLP (approximately 3 years)

Population: Any inebilizumab population included all participants who received at least one dose of inebilizumab either in the RCP or OLP.

Annualized attack rate is defined as total number of AC-determined attacks divided by total person years. Total person-years is calculated as the sum of the person-years for individual participant. Person-year for individual participant = (Date of last day before safety follow-up period - first inebilizumab dose date +1)/365.25. Annualized AC-determined NMOSD attack rate during any exposure to inebilizumab (in RCP and OLP) is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=225 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Annualized AC-determined NMOSD Attack Rate During Any Exposure to Inebilizumab	0.086 Annualized attack rate	—

SECONDARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment received.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the RCP.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP TEAEs	41 Participants	127 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP TESAEs	6 Participants	9 Participants

SECONDARY outcome

Timeframe: Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)

Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=51 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=165 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With TEAEs and TESAEs During OLP TEAEs	45 Participants	144 Participants
Number of Participants With TEAEs and TESAEs During OLP TESAEs	19 Participants	22 Participants

SECONDARY outcome

Timeframe: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)

Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=51 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=165 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) TEAEs	3 Participants	5 Participants
Number of Participants With TEAEs and TESAEs During SFP (Open-label Population) TESAEs	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)

Population: Non-OLP population included all participants who received any dose of study drug, analyzed according to the treatment received in RCP, but did not roll over to OLP.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=5 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=9 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) TEAEs	2 Participants	3 Participants
Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population) TESAEs	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 (Baseline) through Day 197

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment received. 'Number of Participants analyzed' signifies participants who were analyzed for this outcome measure.

Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during RCP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=173 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Hemoglobin (decreased)	0 Participants	2 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Leukocytes (decreased)	1 Participants	11 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Lymphocytes (decreased)	5 Participants	35 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Lymphocytes (increased)	4 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Neutrophils (decreased)	0 Participants	10 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Alanine Aminotransferase (increased)	1 Participants	4 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Aspartate Aminotransferase (increased)	2 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Bilirubin (increased)	2 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Cholesterol (increased)	2 Participants	5 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Creatinine (increased)	1 Participants	5 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Gamma glutamyl transferase (increased)	1 Participants	6 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Glucose (decreased)	1 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Glucose (increased)	5 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Potassium (decreased)	0 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Sodium (decreased)	1 Participants	2 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP Triglycerides (increased)	2 Participants	7 Participants

SECONDARY outcome

Timeframe: Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)

Population: Open-label population included all participants who received at least one dose of study drug during OLP.

Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during OLP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=51 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=165 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Hemoglobin (decreased)	2 Participants	6 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Leukocytes (decreased)	1 Participants	12 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Lymphocytes (decreased)	9 Participants	21 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Lymphocytes (increased)	1 Participants	4 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Neutrophils (decreased)	1 Participants	16 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Alanine aminotransferase (increased)	4 Participants	2 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Albumin (decreased)	0 Participants	3 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Alkaline phosphatase (increased)	1 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Aspartate aminotransferase (increased)	2 Participants	3 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Cholesterol (increased)	1 Participants	5 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Creatinine (increased)	3 Participants	7 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Gamma glutamyl transferase (increased)	1 Participants	10 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Glucose (decreased)	0 Participants	3 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Glucose (increased)	5 Participants	5 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Potassium (decreased)	0 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Potassium (increased)	1 Participants	2 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Sodium (decreased)	2 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Triglycerides (increased)	4 Participants	6 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Urate (increased)	1 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Hemoglobin (increased)	0 Participants	1 Participants
Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP Bilirubin	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).

Time to maximum serum concentration of inebilizumab during RCP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=173 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) Dose 1	0.07 Days Interval 0.07 to 7.0	—
Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) Dose 2	0.07 Days Interval 0.07 to 14.0	—

SECONDARY outcome

Timeframe: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)

Maximum observed serum concentration of inebilizumab during RCP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=173 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) Dose 1	97.7 μg/mL Geometric Coefficient of Variation 37.4	—
Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) Dose 2	108 μg/mL Geometric Coefficient of Variation 45.4	—

SECONDARY outcome

Timeframe: Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)

Area under the serum concentration time curve of the dosing interval (AUC0-14d) of inebilizumab during RCP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=167 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) Dose 1	667 μg*d/mL Geometric Coefficient of Variation 31.3	—
Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) Dose 2	967 μg*d/mL Geometric Coefficient of Variation 39.6	—

SECONDARY outcome

Timeframe: Pre and post dose on Day 1; and on Days 29, 85, and 197

Population: The ITT population included all participants who were randomized, received any study drug, and grouped according to their randomized treatment. 'Number analyzed' signifies the number of participants who had adequate ADA samples.

Number of participants with positive ADA titer to inebilizumab during RCP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=56 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) ADA positive at anytime including baseline (BL)	8 Participants	17 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) ADA positive at BL; not detected post-BL	0 Participants	5 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) ADA positive post-BL; positive at BL	4 Participants	7 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP) ADA positive post-BL; not detected at BL	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)

Population: Open-label population included all participants who received at least one dose of inebilizumab during OLP. 'Number analyzed' signifies the number of participants who had adequate ADA samples.

Number of participants with positive ADA titer to inebilizumab in OLP is reported.

Outcome measures

Outcome measures
Measure	Placebo/Inebilizumab n=51 Participants Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=165 Participants AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) ADA positive at any time including baseline (BL)	9 Participants	22 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) ADA positive at BL; not detected post-BL	0 Participants	5 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) ADA positive post-BL and positive at BL	4 Participants	7 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP) ADA positive post-BL; not detected at BL	5 Participants	10 Participants

Adverse Events

Placebo/Inebilizumab

Serious events: 24 serious events

Other events: 48 other events

Deaths: 1 deaths

Inebilizumab/Inebilizumab

Serious events: 28 serious events

Other events: 138 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical study Information Center

Phone: +1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Viela Bio has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it is understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multicentre publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo/Inebilizumab n=56 participants at risk Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered OLP received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.	Inebilizumab/Inebilizumab n=174 participants at risk AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
Blood and lymphatic system disorders Anaemia	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.3% 11/174 • Number of events 12 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Eye disorders Dry eye	10.7% 6/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.3% 4/174 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Eye disorders Eye pain	8.9% 5/56 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	4.6% 8/174 • Number of events 27 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Abdominal pain	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.7% 3/174 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Constipation	12.5% 7/56 • Number of events 7 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	5.2% 9/174 • Number of events 13 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Diarrhoea	14.3% 8/56 • Number of events 10 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	8.6% 15/174 • Number of events 19 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Gastritis	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.7% 3/174 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Nausea	16.1% 9/56 • Number of events 9 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	8.6% 15/174 • Number of events 31 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Gastrointestinal disorders Vomiting	10.7% 6/56 • Number of events 8 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	5.2% 9/174 • Number of events 11 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
General disorders Fatigue	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.9% 12/174 • Number of events 16 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
General disorders Influenza like illness	7.1% 4/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.7% 3/174 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
General disorders Pyrexia	8.9% 5/56 • Number of events 12 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	5.2% 9/174 • Number of events 12 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Bronchitis	8.9% 5/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.9% 12/174 • Number of events 13 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Conjunctivitis	5.4% 3/56 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Influenza	7.1% 4/56 • Number of events 10 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	9.8% 17/174 • Number of events 20 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Nasopharyngitis	19.6% 11/56 • Number of events 17 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	21.8% 38/174 • Number of events 69 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Oral herpes	7.1% 4/56 • Number of events 8 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Rhinitis	3.6% 2/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	5.2% 9/174 • Number of events 10 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Upper respiratory tract infection	17.9% 10/56 • Number of events 15 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	16.1% 28/174 • Number of events 51 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Infections and infestations Urinary tract infection	35.7% 20/56 • Number of events 54 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	23.0% 40/174 • Number of events 77 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Injury, poisoning and procedural complications Fall	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.3% 11/174 • Number of events 18 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Injury, poisoning and procedural complications Infusion related reaction	16.1% 9/56 • Number of events 16 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	12.6% 22/174 • Number of events 47 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Metabolism and nutrition disorders Hypokalaemia	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	0.57% 1/174 • Number of events 1 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Arthralgia	21.4% 12/56 • Number of events 14 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	16.1% 28/174 • Number of events 37 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 4/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 8 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Muscular weakness	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.3% 4/174 • Number of events 9 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Myalgia	5.4% 3/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Pain in extremity	16.1% 9/56 • Number of events 14 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.3% 11/174 • Number of events 20 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Nervous system disorders Dizziness	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	4.0% 7/174 • Number of events 7 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Nervous system disorders Headache	23.2% 13/56 • Number of events 16 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	17.8% 31/174 • Number of events 82 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Nervous system disorders Hypoaesthesia	3.6% 2/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.9% 12/174 • Number of events 24 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Nervous system disorders Paraesthesia	3.6% 2/56 • Number of events 2 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	6.9% 12/174 • Number of events 15 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Psychiatric disorders Depression	10.7% 6/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	4.6% 8/174 • Number of events 8 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Psychiatric disorders Insomnia	10.7% 6/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	5.7% 10/174 • Number of events 10 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Renal and urinary disorders Micturition urgency	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.1% 2/174 • Number of events 2 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Respiratory, thoracic and mediastinal disorders Cough	10.7% 6/56 • Number of events 15 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	9.8% 17/174 • Number of events 20 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Skin and subcutaneous tissue disorders Alopecia	5.4% 3/56 • Number of events 3 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Skin and subcutaneous tissue disorders Eczema	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.3% 4/174 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Skin and subcutaneous tissue disorders Pruritus	10.7% 6/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	4.0% 7/174 • Number of events 7 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Skin and subcutaneous tissue disorders Rash	7.1% 4/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	4.0% 7/174 • Number of events 11 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Vascular disorders Hypertension	5.4% 3/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	2.9% 5/174 • Number of events 11 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Vascular disorders Hypotension	7.1% 4/56 • Number of events 4 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.1% 2/174 • Number of events 2 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Musculoskeletal and connective tissue disorders Back pain	14.3% 8/56 • Number of events 8 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	13.8% 24/174 • Number of events 38 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.4% 3/56 • Number of events 6 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).	1.7% 3/174 • Number of events 5 • From Day 1 through the end of study (approximately 5 years 10 months) Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).