An Extension Study to Determine Safety and Efficacy for P... | NCT02350816

ID	Type	Description	Link
2014-003960-20	EudraCT Number

Label	Type	Description	Intervention Names
HGT-1410 Q2W in Study HGT-SAN-093 randomized to HGT-1410 Q2W	Active Comparator	Patients in Group 1 will continue HGT-1410 treatment at a dose of 45 mg administered every 2 weeks (Q2W) starting at Week 50, with a cumulative treatment period of up to 42 months (168 weeks) . HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD). HGT-SAN-093 = NCT02060526	Drug: HGT-1410
HGT-1410 Q4W in Study HGT-SAN-093 randomized to HGT-1410 Q4W	Active Comparator	Patients in Group 2 will continue HGT-1410 treatment at a dose of 45 mg administered every 4 weeks (Q4W) starting at Week 52, with a cumulative treatment period of up to 42 months (168 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).	Drug: HGT-1410
no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q2W	Active Comparator	Patients in Group 3A will receive an IDDD following informed consent and will be randomized in a 1:1 allocation ratio to begin HGT-1410 treatment at a dose of 45 mg administered every 2 weeks (Q2W) starting at Week 0 of the extension study, with a cumulative treatment period of up to 30 months (120 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).	Drug: HGT-1410
no-treatment in Study HGT-SAN-093 randomized to HGT-1410 Q4W	Active Comparator	Patients in Group 3B will receive an IDDD following informed consent and will be randomized in a 1:1 allocation ratio to begin HGT-1410 treatment at a dose of 45 mg administered every 4 weeks (Q4W) starting at Week 0 of the extension study, with a cumulative treatment period of up to 30 months (120 weeks). HGT-1410 will be administered intrathecally (IT) by an indwelling intrathecal drug delivery device (IDDD).

Name	Type	Description	Arm Group Labels	Other Names
HGT-1410	Drug	HGT-1410 administered according to Patient Group assignment.	HGT-1410 Q2W in Study HGT-SAN-093 randomized to HGT-1410 Q2W HGT-1410 Q4W in Study HGT-SAN-093 randomized to HGT-1410 Q4W

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. TEAEs was defined as all AEs from the time of initial IDDD implantation (or first dose if earlier) in either Study NCT02060526 (HGT-SAN-093) or Study NCT02350816 (SHP-610-210) to the data cutoff date (28 Jun 2017), or 30 days after the date of the last dose or 2 weeks after the date of device explant (whichever was later) if early termination occurred. Treatment-emergent AEs were summarized by type (serious, life-threatening), severity (mild, moderate, severe) and degree of relationship to investigational product (Intrathecal Drug Delivery Device (IDDD), device surgical procedure, or intraThecal administration of HGT-1410).	From start of study drug administration up to follow-up (Week 276)
Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum	Number of participants with positive anti-rhHNS antibody status in serum were reported.	Up to 120 weeks
Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF)	No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.	Week 0 and 48
Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum	No sufficient PK samples were collected and analyzed due to early termination of the study.	Week 0, 48 and 96
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF)

Measure	Description	Time Frame
Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II)	VABS-II measured adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It was an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measured 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite ((a composite of the other four domains). Scoring was 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The raw scores was converted to domain standard scores (mean 100, SD 15). Higher scores indicate undesirable behavior. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must meet all of the following criteria to be considered eligible for enrollment:

Patient has completed through at least the Week 48 visit of Study HGT-SAN-093
The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board- (IRB-)/ Independent Ethics Committee- (IEC-) approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, as relevant, must be obtained

Exclusion Criteria:

Patients will be excluded from the study if any of the following criteria are met:

The patient, if randomized to treatment in Study HGT-SAN-093, has experienced a decline of more than 20 points in the BSID-III cognitive DQ score between Baseline and the Week 48 visit in Study HGT-SAN-093, AND, upon individual evaluation by the Investigator, has been deemed a treatment failure*
The patient has experienced, in the opinion of the Investigator, a safety or medical issue that contraindicates treatment with HGT-1410, including but not limited to clinically relevant intracranial hypertension, severe infusion-related reactions after treatment with HGT-1410, uncontrollable seizure disorder
The patient has a known hypersensitivity to any of the components of HGT-1410
The patient is enrolled in another clinical study, other than HGT-SAN-093, that involves clinical investigations or use of any investigational product (drug or [intrathecal/spinal] device) within 30 days prior to study enrollment or at any time during the study
The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions
The patient has a condition that is contraindicated as described in the SOPH-A-PORT® Mini S IDDD Instructions for Use, including:
1. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT ® Mini S device
2. The patient's body size is too small to support the size of the SOPH-A-PORT ® Mini S Access Port, as judged by the Investigator
3. The patient's drug therapy requires substances known to be incompatible with the materials of construction
4. The patient has a known or suspected local or general infection
5. The patient is at risk of abnormal bleeding due to a medical condition or therapy
6. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
7. The patient has a functioning CSF shunt device
8. The patient has shown an intolerance to an implanted device
The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator
- All treated patients in Study HGT-SAN-093 will have their cognitive development assessed at the Week 48 Visit in Study HGT-SAN-093. If a decline from Baseline of 20 points or less in the BSID-III DQ score is observed, then the patient may proceed into the Study SHP-610-201 without further evaluation. If a decline from Baseline of more than 20 points in DQ score is observed, then an individual evaluation by the Investigator will occur to determine if the patient is a treatment failure. This individual evaluation will take into account the DQ scores, VABS-II score, physical status, and any other information available for that patient at that time. If the Investigator deems the patient to be a treatment failure, then the patient may not enter the Study SHP-610-201

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota		Minneapolis	Minnesota	55455	United States
University of North Carolina at Chapel Hill

ID	Title	Description
FG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 25, 2017	Mar 20, 2020

ID	Title	Description
BG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
BG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
BG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).
BG003	Group 3B	Participants in Group 3B were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally via IDDD Q4W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0007 BG0016 BG0022 BG0032 BG00417

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. TEAEs was defined as all AEs from the time of initial IDDD implantation (or first dose if earlier) in either Study NCT02060526 (HGT-SAN-093) or Study NCT02350816 (SHP-610-210) to the data cutoff date (28 Jun 2017), or 30 days after the date of the last dose or 2 weeks after the date of device explant (whichever was later) if early termination occurred. Treatment-emergent AEs were summarized by type (serious, life-threatening), severity (mild, moderate, severe) and degree of relationship to investigational product (Intrathecal Drug Delivery Device (IDDD), device surgical procedure, or intraThecal administration of HGT-1410).

Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 [NCT02350816]).

Posted

Number

Participants

From start of study drug administration up to follow-up (Week 276)

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).
OG003	Group 3B	Participants in Group 3B were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally via IDDD Q4W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Units	Counts
Participants	OG0007 OG0016 OG0022 OG003

Title

Denominators

Categories

Participants with TEAEs

Title	Measurements
	OG0007 OG0016 OG0022 OG003

Primary

Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum

Number of participants with positive anti-rhHNS antibody status in serum were reported.

Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 [NCT02350816]). The last observed time point data was presented for outcome measure data.

Posted

Count of Participants

Participants

Up to 120 weeks

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Primary

Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF)

No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.

No sufficient PK samples were collected and analyzed due to early termination of the study.

Posted

Week 0 and 48

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Primary

Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum

No sufficient PK samples were collected and analyzed due to early termination of the study.

No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.

Posted

Week 0, 48 and 96

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Primary

Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF)

Levels of GAG concentration in CSF was reported. Last measurable data was presented for respective participant up to their last observed time point.

Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 [NCT02350816]). Here the number of participants analyzed signifies participants who were evaluable for this measure at specific category.

Posted

Number

micromoles (μmol)

Up to Week 120

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Primary

Levels of Glycosaminoglycan (GAG) Concentration in Urine

Levels of GAG concentration in Urine were reported. Last measurable data was presented for respective participant up to their last available time point.

Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 [NCT02350816]). Here the number of participants analyzed signifies participants who were evaluable for this measure at specific category.

Posted

Number

percentage of GAG

Up to Week 120

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Secondary

Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II)

VABS-II measured adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It was an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measured 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite ((a composite of the other four domains). Scoring was 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The raw scores was converted to domain standard scores (mean 100, SD 15). Higher scores indicate undesirable behavior. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.

No participant was analyzed due to the premature termination of the treatment period of this study.

Posted

Baseline, Week 120

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).

Secondary

Change From Baseline in the Developmental Quotient (DQ) Assessed by Neurocognitive Tests

The development quotient (DQ) was to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). Higher scores are indicative of decreased development. Neurocognitive tests included Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Kaufman Assessment Battery for Children, Second Edition (KABC-II), Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.

No participant was analyzed due to the premature termination of the treatment period of this study.

Posted

Baseline, Week 120

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).

Secondary

Change From Baseline in Total Cortical Grey Matter Volume

The total cortical grey matter volume was assessed by volumetric magnetic resonance imaging (MRI) of the brain. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.

No participant was analyzed due to the premature termination of the treatment period of this study.

Posted

Baseline, Week 120

ID	Title	Description
OG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).
OG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).
OG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG0030 events0 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Adverse drug reaction	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0008 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Device breakage	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Device failure	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site extravasation	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site pain	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pyrexia	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Central nervous system infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Epstein-Barr virus infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pharyngotonsillitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Skin infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Wound infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Incision site swelling	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Tooth injury	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0015 events4 affected6 at risk EG0020 events0 affected2 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Tonsillar hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG0030 events0 affected2 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Diastolic hypertension	Vascular disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Diastolic hypotension	Vascular disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Haematoma	Vascular disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Systolic hypertension	Vascular disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Motion sickness	Ear and labyrinth disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Otorrhoea	Ear and labyrinth disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0006 events3 affected7 at risk EG0011 events1 affected6 at risk EG0021 events1 affected2 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0004 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Salivary gland enlargement	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Non-systematic Assessment	EG00014 events5 affected7 at risk EG0014 events3 affected6 at risk EG0020 events0 affected2 at risk EG003
Adverse drug reaction	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Asthenia	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Catheter site haemorrhage	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Device malfunction	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Impaired healing	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site erythema	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site extravasation	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0015 events2 affected6 at risk EG0021 events1 affected2 at risk EG003
Implant site pain	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site swelling	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Local swelling	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Malaise	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Medical device pain	General disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Pyrexia	General disorders	MedDRA 17.1	Non-systematic Assessment	EG00029 events6 affected7 at risk EG0016 events3 affected6 at risk EG00212 events2 affected2 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Left ventricular hypertrophy	Cardiac disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Acute tonsillitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Bronchopneumonia	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Cellulitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Ear infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0016 events4 affected6 at risk EG0021 events1 affected2 at risk EG003
Folliculitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0006 events3 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Implant site infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Influenza	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Labyrinthitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0014 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Oral infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Otitis media	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0004 events4 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Otitis media acute	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0004 events1 affected7 at risk EG0011 events1 affected6 at risk EG0021 events1 affected2 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Rhinitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG00011 events5 affected7 at risk EG0012 events1 affected6 at risk EG0021 events1 affected2 at risk EG003
Scarlet fever	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Sinusitis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG003
Stitch abscess	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Tinea pedis	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Tonsillitis streptococcal	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG00028 events6 affected7 at risk EG0015 events2 affected6 at risk EG0022 events1 affected2 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Varicella	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Viral infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Wound infection staphylococcal	Infections and infestations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Airway complication of anaesthesia	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0021 events1 affected2 at risk EG003
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG003
Face injury	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0004 events4 affected7 at risk EG0011 events1 affected6 at risk EG0021 events1 affected2 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Incision site complication	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Incision site haemorrhage	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Postoperative fever	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Procedural dizziness	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Procedural headache	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0006 events5 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Tooth injury	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood folate decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Blood pressure diastolic decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0015 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood pressure diastolic increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0014 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood pressure increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood pressure systolic decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0016 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Blood pressure systolic increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Body temperature decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0013 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Body temperature increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
C-reactive protein increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
CSF protein increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
CSF test abnormal	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
CSF white blood cell count increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0003 events1 affected7 at risk EG0014 events3 affected6 at risk EG0020 events0 affected2 at risk EG003
Crystal urine present	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Haematocrit decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Heart rate decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0013 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Heart rate increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0016 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Neutrophil count increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0004 events1 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Platelet count decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Protein total increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Red blood cell count decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Respiratory rate decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Urine uric acid	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Vitamin D decreased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
White blood cell count increased	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
White blood cells urine positive	Investigations	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Aphasia	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Cerebral atrophy	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Demyelination	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Headache	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Lethargy	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Motor dysfunction	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Psychomotor hyperactivity	Nervous system disorders	MedDRA 17.1	Non-systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Decreased interest	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected6 at risk EG0021 events1 affected2 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Irritability	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Sleep terror	Psychiatric disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Vulvovaginal erythema	Reproductive system and breast disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Nasal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Mucocutaneous rash	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pityriasis rosea	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 17.1	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003

ID	Term
D009084	Mucopolysaccharidosis III
D009083	Mucopolysaccharidoses

ID	Term
D002239	Carbohydrate Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D016464	Lysosomal Storage Diseases
D017520	Mucinoses
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks).	7	6	7	7	7
EG001	Group 2	Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks).	6	6	6	6	6
EG002	Group 3A	Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).	2	0	2	2	2
EG003	Group 3B	Participants in Group 3B were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally via IDDD Q4W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks).	2	1	2	2	2