Trial Outcomes & Findings for JAK Inhibitor Treatment in AGS (NCT NCT03921554)

Last Updated: 2025-12-30

Results Overview

The primary objective is to determine if the administration of baricitinib to participants with Aicardi-Goutières Syndrome (AGS) results in a change or stability of the AGS scale from baseline to 52 weeks. The AGS scale is a neurologic scale used to evaluate neurologic function of participants under treatment. The scale includes items for head circumference and developmental milestones. A lower score suggests a worse outcome. The range of scores is from 0 (most severe) to 11 (least severe).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

52 weeks

Results posted on

2025-12-30

Participant Flow

16 patients were enrolled in this investigator-initiated trial (IIT) between June 2019 and February 2020. Between July and September 2021, 20 patients were transitioned from an expanded access study on baricitinib and consented to this IIT. In September 2022, the CHOP IRB allowed transfer of all data collected under the expanded access study to the IIT; 18 additional patients were included in the study dataset, after consent (or waiver, as applicable). Thus, 54 participants total were evaluable.

There has been no significant pre-assignment event.

Participant milestones

Participant milestones
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.
Overall Study STARTED	54
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1
Overall Study Death	3

Baseline Characteristics

JAK Inhibitor Treatment in AGS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.
Age, Categorical <=18 years	49 Participants n=174 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=174 Participants
Age, Categorical >=65 years	0 Participants n=174 Participants
Sex: Female, Male Female	23 Participants n=174 Participants
Sex: Female, Male Male	28 Participants n=174 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=174 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=174 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=174 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=174 Participants
Race (NIH/OMB) Asian	1 Participants n=174 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=174 Participants
Race (NIH/OMB) Black or African American	3 Participants n=174 Participants
Race (NIH/OMB) White	46 Participants n=174 Participants
Race (NIH/OMB) More than one race	1 Participants n=174 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=174 Participants
Region of Enrollment United States	42 Participants n=174 Participants
Region of Enrollment Canada	1 Participants n=174 Participants
Region of Enrollment Poland	6 Participants n=174 Participants
Region of Enrollment United Arab Emirates	1 Participants n=174 Participants
Region of Enrollment United Kingdom	1 Participants n=174 Participants
AGS scale	4.8 score on a scale STANDARD_DEVIATION 3.5 • n=174 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: The overall number of baseline participants totals 51. However, challenges to score the AGS scale at 52 weeks were encountered during the pandemic. Some participants were located outside of the United States and their Visit 210 (52-week time point) was completed by phone and did not allow to gather enough information to complete the AGS severity scale. 45 patients had an AGS score at Visit 210. The mean below is at 52 weeks.

Outcome measures

Outcome measures
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=45 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.	Cohort B: AGS Subjects With Baseline AGS Score 4-8 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 4 and 8 with the AGS severity scale at baseline.	Cohort C: AGS Subjects With Baseline AGS Score 9-11 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 9 and 11 with the AGS severity scale at baseline.
Mean and Standard Deviation (SD) of the AGS Scale at 52 Weeks	5.9 score on a scale Standard Deviation 3.6	—	—

SECONDARY outcome

Timeframe: All longitudinal values are included. ASG scores were observed from 578 days (on some patients) before treatment to 2383 days after treatment start (on some patients). At visit 215 (with median treatment days = 673), the mean AGS score was 6.2 (SD = 3.5).

Population: The Overall Number of Baseline Participants (with genetic confirmation) are included in this analysis.

The AGS scale is a neurologic scale used to evaluate neurologic function of participants under treatment. The scale includes items for head circumference and developmental milestones. A lower score suggests a worse outcome. The range of scores is from 0 (most severe) to 11 (least severe). Longitudinal changes are evaluated, based on measurements collected at baseline, 1 month, 3 months, and every 3 months post-baseline for up to 288 weeks. Participants who transferred from the compassionate use study started treatment under the compassionate use study, which was initiated in 2016. AGS scores were assessed retrospectively for study visits completed under the compassionate use study, based on the study visit notes. The Outcome Measure Time Frame for these subjects may therefore be longer than the study duration specified in the Protocol Section of this study record, as the total time of treatment between the two studies they participated in is longer.

Outcome measures

Outcome measures
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.	Cohort B: AGS Subjects With Baseline AGS Score 4-8 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 4 and 8 with the AGS severity scale at baseline.	Cohort C: AGS Subjects With Baseline AGS Score 9-11 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 9 and 11 with the AGS severity scale at baseline.
Improvement of the AGS Scale From Screening to Treatment Over Time	6.2 score on a scale Standard Deviation 3.5	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: The overall number of baseline participants totals 51. Note one participant did not have a GMFM-88 completed at baseline. Additionally, challenges to score the GMFM-88 scale at 52 weeks were encountered during the pandemic since this assessment could only be completed in person at the time. 35 patients had a GMFM-88 score at Visit 210. The mean below is at 52 weeks.

The Gross Motor Function Measure-88 (GMFM-88) assessment tool includes 88 items, each receiving a score from 0 to 3 (0 = does not initiate; 1 = initiates; 2 = partially completes; 3 = completes). Items span the spectrum of gross motor activities in five dimensions: A: Lying and Rolling (17 items), B: Sitting (20 items), C: Crawling and Kneeling (14 items), D: Standing (13 items), E: Walking, Running, Jumping (24 items). Every dimension score is expressed with a percentage. All dimension scores are then averaged to a total GMFM-88 percentage score, which is an estimate of the participant's gross motor function (0 = low motor function; 100 = high motor function). GMFM-88 is performed every 6 months.

Outcome measures

Outcome measures
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=24 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.	Cohort B: AGS Subjects With Baseline AGS Score 4-8 n=15 Participants Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 4 and 8 with the AGS severity scale at baseline.	Cohort C: AGS Subjects With Baseline AGS Score 9-11 n=11 Participants Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 9 and 11 with the AGS severity scale at baseline.
Improvement of the GMFM-88 Between Screening and Treatment Over Time	6.1 score on a scale Standard Deviation 6.6	30.0 score on a scale Standard Deviation 18.9	57.2 score on a scale Standard Deviation 26.9

SECONDARY outcome

Timeframe: All longitudinal values are included. ISG scores were observed from 431 days before treatment to 2383 days after treatment start. At first on treatment visit (median treatment days = 3), the mean ISG score was 14.4 z-score (Standard Deviation = 12.8).

Population: The Overall Number of Baseline Participants (with genetic confirmation) are included in this analysis.

Interferon (IFN) scores are based on the messenger ribonucleic acid (mRNA) expression of six type I IFN signaling genes (ISG) and represent a surrogate marker for autoinflammation in AGS. Scores are derived from blood sampling, which occurs every three months. ISG scores are elevated in the AGS population and not elevated in healthy controls. The scale has not been published yet but it is hypothesized that a lower value in ISG score reflects a better outcome. Participants who transferred from the compassionate use study started treatment under the compassionate use study, which was initiated in 2016. ISG scores were measured from samples collected under the compassionate use study. The Outcome Measure Time Frame for these subjects may therefore be longer than the study duration specified in the Protocol Section of this study record, as the total time of treatment between the two studies they participated in is longer.

Outcome measures

Outcome measures
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.	Cohort B: AGS Subjects With Baseline AGS Score 4-8 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 4 and 8 with the AGS severity scale at baseline.	Cohort C: AGS Subjects With Baseline AGS Score 9-11 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 9 and 11 with the AGS severity scale at baseline.
Change in Interferon Signaling Gene (ISG) Score Between Screening and Treatment Over Time	14.4 z-score Standard Deviation 12.8	—	—

SECONDARY outcome

Timeframe: All longitudinal values are included. Diary scores were observed from 117 days before treatment to 2476 days after treatment start. At visit 210 (median treatment days = 335), the mean diary average score was 1.2 (SD = 0.4).

Population: The Overall Number of Baseline Participants (with genetic confirmation) are included in this analysis.

The diary disease severity scale is a daily survey that caregivers complete based on the participant's clinical condition during the day and includes items such as uninterrupted sleep, irritability, or skin involvement. Each item is scored from 0 to 4 (0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = more severe symptoms; 4 = severe symptoms). All item scores are then averaged to obtain a total diary score. Participants who transferred from the compassionate use study started treatment under the compassionate use study, which was initiated in 2016. Diaries were already completed and diary scores calculated under the compassionate use study. The Outcome Measure Time Frame for these subjects may therefore be longer than the study duration specified in the Protocol Section of this study record, as the total time of treatment between the two studies they participated in is longer.

Outcome measures

Outcome measures
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 Participants All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.	Cohort B: AGS Subjects With Baseline AGS Score 4-8 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 4 and 8 with the AGS severity scale at baseline.	Cohort C: AGS Subjects With Baseline AGS Score 9-11 Changes in GMFM-88 will be compared between AGS cohorts descriptively. This cohort of participants scored between 9 and 11 with the AGS severity scale at baseline.
Measurement of Disease Severity Assessed by Daily Diary Disease Severity Scale	1.2 score Standard Deviation 0.4	—	—

Adverse Events

Aicardi-Goutières Syndrome Patients Receiving Baricitinib

Serious events: 33 serious events

Other events: 50 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 participants at risk All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.
Blood and lymphatic system disorders Anemia	7.8% 4/51 • Number of events 7 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Thrombocytosis	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Cardiac disorders Cardiac arrest	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Cardiac disorders Sinus bradycardia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Cardiac disorders Sinus tachycardia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Eye disorders Glaucoma	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Abdominal distension	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Constipation	3.9% 2/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Diarrhea	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Dysphagia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Gastrointestinal disorders - Other, Increased salivation	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Vomiting	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
General disorders Fever	9.8% 5/51 • Number of events 7 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
General disorders General disorders and administration site conditions - Other, Poor weight gain	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
General disorders Hypothermia	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
General disorders Multi-organ failure	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Hepatobiliary disorders Hepatic failure	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Bacteremia	2.0% 1/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Bronchial infection	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Enterocolitis infectious	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Aspergillus fumigatus infection	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, COVID-19	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Epstein-Barr virus infection	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Gastroenteritis	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Parainfluenza	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Viral illness	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Lung infection	15.7% 8/51 • Number of events 13 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Meningitis	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Otitis media	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Sepsis	2.0% 1/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Skin infection	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Upper respiratory infection	3.9% 2/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Urinary tract infection	3.9% 2/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Viremia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Wound infection	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, Post surgical hematoma	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, Post-surgical thrombus	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Intraoperative hemorrhage	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Venous injury	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Alkaline phosphatase increased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations CD4 lymphocytes decreased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations CPK increased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Creatinine increased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Investigations - Other, Elevated transaminase/hepatitis	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Lymphocyte count decreased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Neutrophil count decreased	7.8% 4/51 • Number of events 5 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Platelet count decreased	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Acidosis	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Dehydration	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Hypoalbuminemia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Hypoglycemia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Hypokalemia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Metabolism and nutrition disorders Hyponatremia	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Encephalopathy	15.7% 8/51 • Number of events 12 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Lethargy	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Movements involuntary	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Nervous system disorders - Other, Alteration in neurological status	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Nervous system disorders - Other, Central nervous system depression	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Neuralgia	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Seizure	21.6% 11/51 • Number of events 11 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Spasticity	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Agitation	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Irritability	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Psychiatric disorders - Other, Serious behavioral differences	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Renal and urinary disorders Acute kidney injury	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Renal and urinary disorders Chronic kidney disease	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Renal and urinary disorders Renal and urinary disorders - Other, Right vesicoureteral reflux	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Aspiration	3.9% 2/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Respiratory failure	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Bilateral pulmonary embolus	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Abnormal breath holding spell	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Respiratory distress	3.9% 2/51 • Number of events 2 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Rash	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Urticaria	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures Orthopedic surgery	3.9% 2/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures Other major surgery	2.0% 1/51 • Number of events 1 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).

Other adverse events

Other adverse events
Measure	Aicardi-Goutières Syndrome Patients Receiving Baricitinib n=51 participants at risk All participants are treated with baricitinib by mouth or via gastrostomy feeding tube or nasogastric tube as directed by the study doctor. Baricitinib is dosed by participant age, weight range and estimated glomerular filtration rate (eGFR). Dosing formulations in use in this study include 1 mg and 2 mg tablets and is used without splitting. Dispersion is permitted to aid in swallowing.
Blood and lymphatic system disorders Anemia	29.4% 15/51 • Number of events 16 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Thrombocytosis	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Cardiac disorders Sinus tachycardia	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Vomiting	43.1% 22/51 • Number of events 39 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Diarrhea	21.6% 11/51 • Number of events 14 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Constipation	21.6% 11/51 • Number of events 12 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Mucositis oral	5.9% 3/51 • Number of events 8 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Gastroesophageal reflux disease	7.8% 4/51 • Number of events 5 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Gastrointestinal disorders - Other, Increased salivation	7.8% 4/51 • Number of events 5 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Gastrointestinal disorders Abdominal pain	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
General disorders Fever	47.1% 24/51 • Number of events 68 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Immune system disorders Allergic reaction	9.8% 5/51 • Number of events 5 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Upper respiratory infection	74.5% 38/51 • Number of events 121 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Urinary tract infection	33.3% 17/51 • Number of events 53 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Otitis media	29.4% 15/51 • Number of events 42 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Lung infection	29.4% 15/51 • Number of events 30 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Skin infection	31.4% 16/51 • Number of events 27 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Gastroenteritis	23.5% 12/51 • Number of events 20 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, BK viruria	29.4% 15/51 • Number of events 15 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Pharyngitis	17.6% 9/51 • Number of events 12 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Thrush	11.8% 6/51 • Number of events 12 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, COVID-19	19.6% 10/51 • Number of events 11 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Sinusitis	19.6% 10/51 • Number of events 11 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Bronchial infection	13.7% 7/51 • Number of events 9 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Viral illness	13.7% 7/51 • Number of events 9 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Viremia	15.7% 8/51 • Number of events 8 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Eye infection	11.8% 6/51 • Number of events 7 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Infections and infestations Infections and infestations - Other, Exposure to Varicella, no infection	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, Skin injury	15.7% 8/51 • Number of events 11 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Fracture	9.8% 5/51 • Number of events 8 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, G tube complications	13.7% 7/51 • Number of events 8 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Injury, poisoning and procedural complications Wrist fracture	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Neutrophil count decreased	19.6% 10/51 • Number of events 14 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations CPK increased	11.8% 6/51 • Number of events 9 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Investigations - Other, Low vitamin D	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Investigations - Other, Elevated liver enzymes	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Investigations Thyroid stimulating hormone increased	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, Hip dislocation	7.8% 4/51 • Number of events 6 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Musculoskeletal and connective tissue disorders Scoliosis	11.8% 6/51 • Number of events 6 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, Hip subluxation	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Seizure	15.7% 8/51 • Number of events 10 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Encephalopathy	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Headache	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Nervous system disorders Movements involuntary	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Agitation	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Irritability	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Psychiatric disorders Insomnia	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Renal and urinary disorders Hematuria	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Cough	35.3% 18/51 • Number of events 29 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Nasal congestion	25.5% 13/51 • Number of events 26 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Rhinorrhea	15.7% 8/51 • Number of events 9 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Sinus disorder	7.8% 4/51 • Number of events 5 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Respiratory, thoracic and mediastinal disorders Sleep apnea	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Rash	13.7% 7/51 • Number of events 9 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Eczema	13.7% 7/51 • Number of events 8 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Skin ulceration	7.8% 4/51 • Number of events 7 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Acne	7.8% 4/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Seborrhea	5.9% 3/51 • Number of events 3 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures Orthopedic surgery	27.5% 14/51 • Number of events 33 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures Other major surgery	25.5% 13/51 • Number of events 17 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures G-tube	17.6% 9/51 • Number of events 14 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Surgical and medical procedures Tone invasive	7.8% 4/51 • Number of events 6 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).
Vascular disorders Hypertension	5.9% 3/51 • Number of events 4 • Adverse event data collection started for each subject at their Drug Initiation visit (Visit 2). Adverse events were monitored every three months (at every study visit, and more often in case of SAE) and until one month after cessation of treatment. Subjects were treated for up to approximately 288 weeks. Subjects who were transferred from the compassionate use study started treatment before this IIT start date and continued treatment per the study schedule for up to approximately 288 weeks. Adverse events were collected and updated at every study visit (approximately every three months) as well as by phone or email communication throughout each subject's participation to the study as needed. Adverse Events were assessed in the Safety Population (51 participants) and All-Cause Mortality was assessed for all enrolled participants (54 participants).

Additional Information

Dr. Adeline Vanderver

Children's Hospital of Philadelphia

Phone: 215-590-1719

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place