Trial Outcomes & Findings for CHAMP: Study of NVK-002 in Children With Myopia (NCT NCT03350620)

NCT ID: NCT03350620

Last Updated: 2024-11-27

Results Overview

Number of subjects' eyes that show \< 0.50 D myopia progression (SER, spherical equivalent refraction) at the Month 36 visit.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 670 participants
• Primary outcome timeframe: 36 Months
• Results posted on: 2024-11-27

Participant Flow

Enrolled subjects who did not meet the inclusion criteria or met the exclusion criteria were not randomized.

Participant milestones

Measure	NVK-002 Concentration 1 Stage 1: Subjects will be randomized to NVK-002 Concentration 1 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	NVK-002 Concentration 2 Stage 1: Subjects will be randomized to NVK-002 Concentration 2 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Vehicle (Placebo) Stage 1: Subjects will be randomized to Vehicle (Placebo) Stage 2: Subjects will be re-randomized to one of the two experimental NVK-002 treatment arms Placebo: Vehicle (placebo) will be administered, once daily (QD)
Stage 1 STARTED	164	247	165
Stage 1 COMPLETED	127	207	143
Stage 1 NOT COMPLETED	37	40	22
Stage 2 STARTED	159	162	99
Stage 2 COMPLETED	156	153	96
Stage 2 NOT COMPLETED	3	9	3

Reasons for withdrawal

Measure	NVK-002 Concentration 1 Stage 1: Subjects will be randomized to NVK-002 Concentration 1 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	NVK-002 Concentration 2 Stage 1: Subjects will be randomized to NVK-002 Concentration 2 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Vehicle (Placebo) Stage 1: Subjects will be randomized to Vehicle (Placebo) Stage 2: Subjects will be re-randomized to one of the two experimental NVK-002 treatment arms Placebo: Vehicle (placebo) will be administered, once daily (QD)
Stage 2 Adverse Event	0	1	1
Stage 2 Lack of Efficacy	0	2	0
Stage 2 Lost to Follow-up	1	2	2
Stage 2 unable to visit (1); used prohibited concomitant medication / withdrew consent (4); relocation (1).	2	4	0

Baseline Characteristics

CHAMP: Study of NVK-002 in Children With Myopia

Baseline characteristics by cohort

Measure	NVK-002 Concentration 1 n=164 Participants Stage 1: Subjects will be randomized to NVK-002 Concentration 1 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	NVK-002 Concentration 2 n=247 Participants Stage 1: Subjects will be randomized to NVK-002 Concentration 2 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Vehicle (Placebo) n=165 Participants Stage 1: Subjects will be randomized to Vehicle (Placebo) Stage 2: Subjects will be re-randomized to one of the two experimental NVK-002 treatment arms Placebo: Vehicle (placebo) will be administered, once daily (QD)	Total n=576 Participants Total of all reporting groups
Age, Continuous	9.0 years STANDARD_DEVIATION 2.1 • n=5 Participants	9.0 years STANDARD_DEVIATION 2.1 • n=7 Participants	8.8 years STANDARD_DEVIATION 1.8 • n=5 Participants	8.9 years STANDARD_DEVIATION 2.0 • n=4 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	136 Participants n=7 Participants	94 Participants n=5 Participants	315 Participants n=4 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	111 Participants n=7 Participants	71 Participants n=5 Participants	261 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Asian	29 Participants n=5 Participants	54 Participants n=7 Participants	26 Participants n=5 Participants	109 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	31 Participants n=7 Participants	27 Participants n=5 Participants	81 Participants n=4 Participants
Race (NIH/OMB) White	84 Participants n=5 Participants	132 Participants n=7 Participants	93 Participants n=5 Participants	309 Participants n=4 Participants
Race (NIH/OMB) More than one race	15 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	20 Participants n=7 Participants	7 Participants n=5 Participants	36 Participants n=4 Participants
Region of Enrollment Europe	34 participants n=5 Participants	48 participants n=7 Participants	29 participants n=5 Participants	111 participants n=4 Participants
Region of Enrollment United States	130 participants n=5 Participants	199 participants n=7 Participants	136 participants n=5 Participants	465 participants n=4 Participants
SER	-2.25 Diopter n=5 Participants	-2.33 Diopter n=7 Participants	-2.41 Diopter n=5 Participants	-2.33 Diopter n=4 Participants

PRIMARY outcome

Timeframe: 36 Months

Population: ITT

Number of subjects' eyes that show < 0.50 D myopia progression (SER, spherical equivalent refraction) at the Month 36 visit.

Outcome measures

Measure	NVK-002 Concentration 1 n=328 participants' eyes Stage 1: Subjects will be randomized to NVK-002 Concentration 1 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	NVK-002 Concentration 2 n=494 participants' eyes Stage 1: Subjects will be randomized to NVK-002 Concentration 2 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Vehicle (Placebo) n=330 participants' eyes Stage 1: Subjects will be randomized to Vehicle (Placebo) Stage 2: Subjects will be re-randomized to one of the two experimental NVK-002 treatment arms Placebo: Vehicle (placebo) will be administered, once daily (QD)
Number of Subjects' Eyes That Show < 0.50 D Myopia Progression (SER, Spherical Equivalent Refraction) at the Month 36 Visit	79 participants' eyes	106 participants' eyes	61 participants' eyes

SECONDARY outcome

Timeframe: Month 36

Population: ITT

Change from baseline in SER (spherical equivalent refraction).

Outcome measures

Measure	NVK-002 Concentration 1 n=328 Participants' eyes Stage 1: Subjects will be randomized to NVK-002 Concentration 1 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	NVK-002 Concentration 2 n=494 Participants' eyes Stage 1: Subjects will be randomized to NVK-002 Concentration 2 Stage 2: Subjects will be re-randomized to one of the three treatment arms. NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Vehicle (Placebo) n=330 Participants' eyes Stage 1: Subjects will be randomized to Vehicle (Placebo) Stage 2: Subjects will be re-randomized to one of the two experimental NVK-002 treatment arms Placebo: Vehicle (placebo) will be administered, once daily (QD)
Change From Baseline in SER (Spherical Equivalent Refraction)	-0.85 Diopter Interval -3.28 to 1.22	-1.02 Diopter Interval -3.94 to 0.89	-1.10 Diopter Interval -4.44 to 3.6

Adverse Events

Stage 1: NVK-002 Concentration 1

Serious events: 1 serious events

Other events: 56 other events

Deaths: 0 deaths

Stage 1: NVK-002 Concentration 2

Serious events: 8 serious events

Other events: 92 other events

Deaths: 0 deaths

Stage 1: Vehicle (Placebo)

Serious events: 4 serious events

Other events: 75 other events

Deaths: 0 deaths

Stage 2: NVK-002 Concentration 1

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Stage 2: NVK-002 Concentration 2

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Stage 2: Vehicle (Placebo)

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Stage 1: NVK-002 Concentration 1 n=164 participants at risk Stage 1: Subjects randomized to NVK-002 Concentration 1 NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	Stage 1: NVK-002 Concentration 2 n=247 participants at risk Stage 1: Subjects randomized to NVK-002 Concentration 2 NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Stage 1: Vehicle (Placebo) n=162 participants at risk Stage 1: Subjects randomized to Vehicle (Placebo) Placebo: Vehicle (placebo) will be administered, once daily (QD). Note: N=162 for the safety set (see comment in participant flow)	Stage 2: NVK-002 Concentration 1 n=159 participants at risk Stage 2: Subjects randomized to NVK-002 Concentration 1 include those from Stage 1 NVK-002 concentration, Stage 1 NVK-002 concentration 2 and Stage 1 Vehicle (Placebo).	Stage 2: NVK-002 Concentration 2 n=162 participants at risk Stage 2: Subjects randomized to NVK-002 Concentration 2 include those from Stage 1 NVK-002 concentration 1, NVK-002 concentration 2, and Stage 1 Vehicle (Placebo).	Stage 2: Vehicle (Placebo) n=99 participants at risk Stage 2: Subjects randomized to Vehicle (Placebo) include those from Stage 1 NVK-002 concentration 1 and Stage 1 NVK-002 concentration 2.
Infections and infestations Appendicitis	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.81% 2/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.63% 1/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations COVIV-19	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.62% 1/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations Parainfluenza	0.61% 1/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations Pneumonia	0.61% 1/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Gastrointestinal disorders Abdominal pain	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Gastrointestinal disorders Anal fisuure	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Gastrointestinal disorders Ascites	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders suicidal ideation	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders suicide attempt	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.63% 1/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Nervous system disorders seizure	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.62% 1/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.63% 1/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Renal and urinary disorders acute kidney injury	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.62% 1/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Congenital, familial and genetic disorders developmental hip dysplasia	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) brain neoplasm malignant	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Hepatobiliary disorders cholecystitis	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Gastrointestinal disorders rectal hemorrhage	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.40% 1/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders Depression	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.0% 1/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders Disruptive mood dysregulation disorder	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.0% 1/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders Mania	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.62% 1/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Psychiatric disorders Ankle fracture	0.00% 0/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.62% 1/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.

Other adverse events

Measure	Stage 1: NVK-002 Concentration 1 n=164 participants at risk Stage 1: Subjects randomized to NVK-002 Concentration 1 NVK-002 Concentration 1: Study medication will be administered, once daily (QD)	Stage 1: NVK-002 Concentration 2 n=247 participants at risk Stage 1: Subjects randomized to NVK-002 Concentration 2 NVK-002 Concentration 2: Study medication will be administered, once daily (QD)	Stage 1: Vehicle (Placebo) n=162 participants at risk Stage 1: Subjects randomized to Vehicle (Placebo) Placebo: Vehicle (placebo) will be administered, once daily (QD). Note: N=162 for the safety set (see comment in participant flow)	Stage 2: NVK-002 Concentration 1 n=159 participants at risk Stage 2: Subjects randomized to NVK-002 Concentration 1 include those from Stage 1 NVK-002 concentration, Stage 1 NVK-002 concentration 2 and Stage 1 Vehicle (Placebo).	Stage 2: NVK-002 Concentration 2 n=162 participants at risk Stage 2: Subjects randomized to NVK-002 Concentration 2 include those from Stage 1 NVK-002 concentration 1, NVK-002 concentration 2, and Stage 1 Vehicle (Placebo).	Stage 2: Vehicle (Placebo) n=99 participants at risk Stage 2: Subjects randomized to Vehicle (Placebo) include those from Stage 1 NVK-002 concentration 1 and Stage 1 NVK-002 concentration 2.
Infections and infestations nasopharyngitis	10.4% 17/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	12.1% 30/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	13.6% 22/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.8% 14/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.1% 5/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	6.1% 6/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations COVID-19	5.5% 9/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	10.9% 27/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	11.1% 18/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.8% 14/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.0% 13/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.1% 8/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations influenza	3.7% 6/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.2% 8/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	7.4% 12/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	2.5% 4/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	2.0% 2/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Infections and infestations hordeolum	1.8% 3/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	4.0% 10/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	6.8% 11/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.3% 2/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.0% 1/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Eye disorders ocular hyperemia	2.4% 4/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.2% 8/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	6.2% 10/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Nervous system disorders headache	8.5% 14/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	9.3% 23/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.6% 14/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.1% 5/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.0% 1/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Respiratory, thoracic and mediastinal disorders cough	1.8% 3/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	2.8% 7/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	5.6% 9/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.3% 2/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	0.00% 0/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
Immune system disorders seasonal allergy	7.3% 12/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	5.7% 14/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	5.6% 9/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.1% 5/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	2.5% 4/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.0% 1/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.
General disorders pyrexia	4.9% 8/164 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	8.5% 21/247 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	3.7% 6/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.9% 3/159 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	1.2% 2/162 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.	2.0% 2/99 • 3 years (Stage 1) and 1 year (Stage 2) Treatment-emergent adverse events (TEAEs) are defined as any new or worsening of existing adverse events that occur or worsen between the first dose date of a specific stage and the last dose date of the same stage. All-cause mortality, serious AE and other AE reporting are based on the Safety Set. The Safety Set (SS) will include all subjects who were administered at least one dose of study medication in Stage 1 or Stage 2.

Additional Information

VP of Clinical Development

Vyluma, Inc

Phone: 9083677400

Email: info@vyluma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place