Trial Outcomes & Findings for Gene Therapy for Wiskott-Aldrich Syndrome (NCT NCT01515462)

Last Updated: 2025-04-04

Results Overview

The absence of prolonged aplasia (defined as ANC \<0.5×10\^9/L \[\<500/μL\] at Day +60, with no evidence of BM recovery and requiring backup administration) was assumed as demonstrating the safety of the RIC regimen.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Results posted on

2025-04-04

Participant Flow

Participant milestones

Participant milestones
Measure	OTL-103 Gene Therapy Eligible subjects will receive intravenous (IV) infusion of OTL-103 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included OTL-103: OTL-103 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Gene Therapy for Wiskott-Aldrich Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OTL-103 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of OTL-103 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included OTL-103: OTL-103 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Age, Categorical <=18 years	8 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Italy	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Population: Mobilization Set (MS) for Safety analysis. Intent-to-treat (ITT) population for Efficacy analysis. All eight enrolled participants were included in the ITT and MS populations

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Safety of Reduced Conditioning Regimen	8 Participants

PRIMARY outcome

Timeframe: after 48 hours after Telethon003 infusion

Safety and tolerability of lentiviral-transduced cell infusion. This will be evaluated on the basis of adverse events reporting and monitoring of the systemic reactions to cell infusion.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Safety of Lentivirus Gene Transfer Into HSC	8 Participants

PRIMARY outcome

Timeframe: at 1 year after Telethon003 infusion

Population: count of participants with sustained engraftment of genetically corrected HSPCs

Engraftment is characterized by the presence of gene modified cells in the BM or PB compartments. The main indicator of gene correction is detection of the WAS LVV sequences in the HSPCs and their progeny. The VCN, which is the mean number of integrated copies of the vector sequences per cell genome, was measured using PCR-based methods in DNA samples extracted from BM and PB cell populations at various timepoints post-treatment. Adequate engraftment was defined as either ≥0.04 VCN/cell in BM CD34+ cells or ≥0.01 VCN/cell in PB CD3+ cells.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow	8 Participants

PRIMARY outcome

Timeframe: Median duration: 11.1 years (range: 8.01 -13.3 years)

The percentage of subjects who present the proportion of PB cells expressing WASP was assessed by flow cytometry analysis.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Presence of Detectable Vector-derived WASP	8 Participants

PRIMARY outcome

Timeframe: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Improvement in in vitro T-cell proliferation was assessed upon stimulation with 3 doses of anti-immobilized CD3 (CD3i) monoclonal antibodies ≥1 year after Telethon003 infusion (as compared with pre-GT values) in PBMC and/or T-cell lines. The degree of correction was evaluated with respect to healthy controls.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Improved T-cell Functions	8 Participants

PRIMARY outcome

Timeframe: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

The ability to mount a protective humoral response to at least 4 out of 5 nominal antigens including antibodies to T-cell dependent antigens and conjugated or unconjugated polysaccharide antigens was measured after vaccination (planned \>1 year after Telethon003 infusion). If results were available on n \<5 antigens, the rule of at least n-1 applied to define success.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Antigen-specific Responses to Vaccination	7 participants

PRIMARY outcome

Timeframe: up to 3 years after Telethon003 infusion

Sustained increase in platelet count compared to baseline, analyzing the individual longitudinal profile

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Improved Platelet Count and MPV Normalization	8 Participants

PRIMARY outcome

Timeframe: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Participant survival was monitored throughout the study.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Overall Survival	8 Participants

SECONDARY outcome

Timeframe: up to 3 years after Telethon003 infusion

Anti-WASP and anti-HIV-1 antibodies (anti-p24) were monitored to evaluate response to transgene and to vector, respectively.

Outcome measures

Outcome measures
Measure	TLT003 Gene Therapy n=8 Participants Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included TLT003: TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Lack of Immune Response to Transgene	8 Participants

Adverse Events

OTL-103 Gene Therapy

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OTL-103 Gene Therapy n=8 participants at risk Eligible subjects will receive intravenous (IV) infusion of OTL-103 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included OTL-103: OTL-103 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Blood and lymphatic system disorders Mesenteric lymphadenitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Neutropenia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Pyrexia	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Food Allergy	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Device related infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Gastroenteritis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pneumonia aspiration	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Appendicitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Aspergillus infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Bacterial sepsis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Cellulitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Device related sepsis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Gastroenteritis rotavirus	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Influenza	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Otitis media	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pneumonia bacterial	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Tooth Abscess	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Tracheitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Viral infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Head injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Electrolyte imbalance	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Irritability	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.

Other adverse events

Other adverse events
Measure	OTL-103 Gene Therapy n=8 participants at risk Eligible subjects will receive intravenous (IV) infusion of OTL-103 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included OTL-103: OTL-103 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Blood and lymphatic system disorders Lymphadenopathy	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Eosinophilia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Neutropenia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Anaemia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Febrile neutropenia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Immune thrombocytopenia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Polycythaemia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Coagulopathy	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Disseminated intravascular coagulation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Neutrophilia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Blood and lymphatic system disorders Splenomegaly	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Cardiac disorders Sinus tachycardia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Cardiac disorders Supraventricular extrasystoles	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Congenital, familial and genetic disorders Phimosis	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Congenital, familial and genetic disorders Familial mediterranean fever	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Congenital, familial and genetic disorders Lymphatic malformation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Congenital, familial and genetic disorders Retinal anomaly congenital	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Ear and labyrinth disorders Ear pain	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Ear and labyrinth disorders Deafness neurosensory	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Ear and labyrinth disorders Middle ear inflammation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Ear and labyrinth disorders Tympanic membrane perforation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Endocrine disorders Adrenal insufficiency	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Endocrine disorders Graves' disease	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Endocrine disorders Hypoaldosteronism	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Endocrine disorders Hypothyroidism	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Endocrine disorders Precocious puberty	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Eye inflammation	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Conjunctivitis allergic	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Blepharitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Dyschromatopsia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Eczema eyelids	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Astigmatism	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Conjunctival haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Conjunctival hyperaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Eyelid ptosis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Keratitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Myopia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Periorbital oedema	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Retinopathy	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Eye disorders Visual acuity reduced	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Diarrhoea	87.5% 7/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Gingival bleeding	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Haematochezia	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Vomiting	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Dental caries	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Mouth haemorrhage	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Anal fissure	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Abdominal pain	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Diarrhoea haemorrhagic	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Gastrointestinal haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Malocclusion	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Aphthous ulcer	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Constipation	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Oral pain	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Stomatitis	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Tooth discolouration	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Anal haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Crohn's disease	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Dysphagia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Enterocutaneous fistula	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Gastric disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Gastric haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Gingival disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Ileal ulcer	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Inguinal hernia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Large intestinal ulcer	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Gastrointestinal disorders Oral disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Pyrexia	100.0% 8/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Inflammation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Catheter site haemorrhage	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Swelling face	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Vaccination site inflammation	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Catheter site erythema	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Catheter site inflammation	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Catheter site rash	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Adverse drug reaction	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Asthenia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Catheter site mass	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Drug withdrawal syndrome	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Feeling abnormal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Influenza like illness	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
General disorders Non-cardiac chest pain	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Hepatobiliary disorders Hepatomegaly	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Hepatobiliary disorders Gallbladder disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Hepatobiliary disorders Hypertransaminasaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Allergy to immunoglobulin therapy	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Food allergy	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Hypersensitivity	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Drug hypersensitivity	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Immune system disorders Hypogammaglobulinaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Upper respiratory tract infection	100.0% 8/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Rhinitis	75.0% 6/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Otitis media	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Otitis media acute	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pharyngitis	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Conjunctivitis	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Gastroenteritis	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Ear infection	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Influenza	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Respiratory tract infection	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Sinusitis	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Cytomegalovirus infection reactivation	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pneumonia	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Coronavirus infection	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pharyngitis streptococcal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Skin infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Tooth abscess	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Eye infection	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Amoebic dysentery	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Bacterial disease carrier	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Catheter site infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Diarrhoea infectious	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Folliculitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Nasopharyngitis	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Oral candidiasis	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Oral herpes	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Tracheitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Urinary tract infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Viral infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Abscess limb	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Bronchitis	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations COVID-19	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Cytomegalovirus infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Cytomegalovirus viraemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Epstein-Barr virus infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Escherichia urinary tract infection	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Gastroenteritis viral	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Paronychia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pharyngotonsillitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Urethritis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Urinary tract infection bacterial	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Viral rhinits	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Amoebiasis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Bordetella infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Chronic tonisllitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Conjunctivitis bacterial	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Coxsackie vital infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Ear infection fungal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Enterobiasis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Enterococcal sepsis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Enterocolitis viral	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Fungal skin infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Genital infection fungal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Gingivitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Herpes virus infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Infection parasitic	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Laryngitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Laryngopharyngitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Lice infestation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Measles	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Molluscum contagiosum	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Omphalitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Otitis externa	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pneumocystis jirovecii pneumonia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pneumonia cytomegaloviral	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Pulpitis dental	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Respiratory tract infection viral	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Varicella	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Infections and infestations Viral upper respiratory tract infection	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Head injury	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Limb injury	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Traumatic haematoma	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Face injury	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Hand fracture	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Torus fracture	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Ankle fracture	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Arthropod bite	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Craniocerebral injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Eyelid injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Fall	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Infusion related reaction	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Joint injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Lip injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Tibia fracture	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Traumatic haemorrhage	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Injury, poisoning and procedural complications Vaccination complication	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Anti-platelet antibody positive	100.0% 8/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Staphylococcus test positive	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Hepatic enzyme increased	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Antineutrophil cytoplasmic antibody positive	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Streptococcus test positive	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Antinuclear antibody positive	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood immunoglonulin E increased	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood alkaline phosphatase increased	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Cytomegalovirus test positive	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Haemophilus test positive	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Pseudomonas test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Smooth muscle antibody positive	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Vitamin D decreased	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood calcium decreased	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Clostridium test positive	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Electrophoresis protein abnormal	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Intraocular pressure increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Adenovirus test positive	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Anti-saccharomyces cerevisiae antibody test positive	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations C-reactive protein increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Coombs direct test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Epstein-Barr virus test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Inflammatory marker increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Serum ferritin decreased	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Serum ferritin increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Acinetobacter test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Anti-thyroid antibody positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Anti-transglutaminase antibody increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Antimitochondrial antibody positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Antiribosomal P antibody positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Aspartate aminotransferase increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood beta-D-glucan abnormal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood bicarbonate decreased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood bilirubin increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood cholesterol increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood creatinine increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood culture positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood folate decreased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood glucose increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood iron decreased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Blood thyroid stimulating hormone increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Candida test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Chest X-ray abnormal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Dehydroepiandrosterone decreased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Double stranded DNA antibody positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Enterobacter test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Faecal calprotectin increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Lymph nodes scan abnormal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Moraxella test positive	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Occult blood	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Spirometry abnormal	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Transaminases increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Tri-iodothyronine increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Investigations Vitamin B12 increased	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hypokalaemia	75.0% 6/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Iron deficiency	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Obesity	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Vitamin D deficiency	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hypoalbuminaemia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hypertriglyceridaemia	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hypomagnesaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hyponatraemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Insulin resistance	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Feeding intolerance	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hyperglycaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Hyperkalaemia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Metabolism and nutrition disorders Weight gain poor	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Arthritis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Osteitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Back pain	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Pain in extremity	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Joint swelling	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Musculoskeletal and connective tissue disorders Short stature	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Nervous system disorders Headache	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Nervous system disorders Cerebral cyst	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Nervous system disorders Dyskinesia	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Nervous system disorders Speech disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Aggression	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Anxiety	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Attention deficit hyperactivity disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Autism spectrum disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Behaviour disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Depression	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Drug dependece	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Enuresis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Psychiatric disorders Sleep disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Haematuria	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Proteinuria	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Pyelocaliectasis	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Acute kidney injury	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Nephrolothiasis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Pollakiuria	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Polyuria	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Renal and urinary disorders Renal impairment	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Reproductive system and breast disorders Balanoposthitis	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Reproductive system and breast disorders Acquired phimosis	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Reproductive system and breast disorders Penile erythema	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Reproductive system and breast disorders Perineal erythema	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Reproductive system and breast disorders Varicocele	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Cough	62.5% 5/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Wheezing	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Respiratory distress	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Asthma	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Stridor	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Aspiration	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Lung consolidation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Nasal polyps	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Nasal varices	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Painful respiration	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Productive cough	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Reflux laryngitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Restrictive pulmonary disease	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Petechiae	87.5% 7/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Eczema	75.0% 6/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Rash	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Drug eruption	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dermatitis	50.0% 4/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dermatitis diaper	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dermatitis allergic	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Urticaria	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dermatitis atopic	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Pruritus	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Rash erythematous	37.5% 3/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Erythema	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Pityriasis alba	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dermatitis contact	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Dry skin	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Erythema nodosum	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Perioral dermatitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Pityriasis rosea	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Purpura	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Rash pruritic	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Skin discolouration	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Skin fissures	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Skin and subcutaneous tissue disorders Skin lesion	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Vascular disorders Vasculitis	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Vascular disorders Hypertension	12.5% 1/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.
Vascular disorders Phlebitis	25.0% 2/8 • Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years. For each AE, the Investigator specified the date of onset, intensity, action taken, corrective therapy given, outcome, assessment regarding the causal relationship with the IMP. Adverse events were graded according to the CTCAE scale. Events meeting the Hy's law criteria ( \[ALT\] ≥3×upper limit of normal \[ULN\] and bilirubin ≥2×ULN \[\>35% direct bilirubin\] or ALT ≥3×ULN and international normalized ratio \>1.5, if international normalized ratio measured) were to be reported as SAEs.

Additional Information

Sean Russell

Fondazione Telethon ETS

Phone: +39 02 2022 17210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Principal Investigator shall send any manuscript to the Sponsor/FT prior to its submission for publication. The Sponsor/FT shall have 45 days (silence=consent), from receipt of the manuscript, during which time any manuscript amendments may be suggested. The Principal Investigator shall accept the incorporation into the publication of any comments that do not affect the reliability of data, as well as the rights, safety and well-being of the patients.
Publication restrictions are in place

Restriction type: OTHER