Trial Outcomes & Findings for An Extension Study to Determine Safety and Efficacy for Pediatric Patients With MPS Type IIIA Disease Who Participated in Study HGT-SAN-093. (NCT NCT02350816)

Last Updated: 2021-06-11

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

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

Results posted on

2021-06-11

Participant Flow

The first participant enrolled in the study on 08 April 2015 and last participant last follow-up on 12 April 2019.

A total of 17 participants were enrolled and completed treatment period in the study.

Participant milestones

Participant milestones
Measure	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).	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).	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).	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).
Overall Study STARTED	7	6	2	2
Overall Study COMPLETED	7	6	2	2
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Extension Study to Determine Safety and Efficacy for Pediatric Patients With MPS Type IIIA Disease Who Participated in Study HGT-SAN-093.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 n=7 Participants 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).	Group 2 n=6 Participants 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).	Group 3A n=2 Participants 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).	Group 3B n=2 Participants 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).	Total n=17 Participants Total of all reporting groups
Age, Continuous	29.64 Months STANDARD_DEVIATION 9.989 • n=5 Participants	31.62 Months STANDARD_DEVIATION 8.598 • n=7 Participants	40.40 Months STANDARD_DEVIATION 5.798 • n=5 Participants	36.95 Months STANDARD_DEVIATION 7.142 • n=4 Participants	32.47 Months STANDARD_DEVIATION 8.941 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	7 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	17 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

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

Population: 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 \[NCT02350816\]).

Outcome measures

Outcome measures
Measure	Group 1 n=7 Participants 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).	Group 2 n=6 Participants 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).	Group 3A n=2 Participants 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).	Group 3B n=2 Participants 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).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with TEAEs	7 Participants	6 Participants	2 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Serious TEAEs	6 Participants	6 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Life-Threatening TEAEs	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Mild TEAEs	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Moderate TEAEs	4 Participants	4 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Severe TEAEs	3 Participants	2 Participants	9 Participants	9 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with HGT-1410 Related TEAEs	5 Participants	5 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with Surgery Related TEAEs	6 Participants	6 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with IDDD Related TEAEs	5 Participants	6 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug Participants with IT Administration Related TEAEs	3 Participants	6 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 120 weeks

Population: 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.

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

Outcome measures

Outcome measures
Measure	Group 1 n=7 Participants 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).	Group 2 n=6 Participants 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).	Group 3A n=2 Participants 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).	Group 3B n=2 Participants 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).
Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum	7 Participants	6 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Week 0 and 48

Population: 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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Week 0, 48 and 96

Population: 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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Week 120

Population: 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.

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

Outcome measures

Outcome measures
Measure	Group 1 n=7 Participants 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).	Group 2 n=6 Participants 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).	Group 3A n=2 Participants 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).	Group 3B n=2 Participants 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).
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 1: Week 16	—	—	—	3.67 micromoles (μmol)
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 2: Week 60	—	1.52 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 3: Week 86	0.698 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 4: Week 72	—	1.5 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 5: Week 44	—	—	0.592 micromoles (μmol)	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 6: Week 72	2.62 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 7: Week 120	—	1.26 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 8: Week 72	—	2.49 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 9: Week 72	—	1.77 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 10: Week 72	—	2.13 micromoles (μmol)	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 11: Week 60	1.35 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 12: Week 96	0.491 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 13: Week 84	2.84 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 14: Week 62	4.05 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 15: Week 60	1.63 micromoles (μmol)	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 16: Week 20	—	—	0.699 micromoles (μmol)	—
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) Participant 17: Week 8	—	—	—	2.59 micromoles (μmol)

PRIMARY outcome

Timeframe: Up to Week 120

Population: 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.

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

Outcome measures

Outcome measures
Measure	Group 1 n=7 Participants 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).	Group 2 n=6 Participants 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).	Group 3A n=2 Participants 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).	Group 3B n=2 Participants 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).
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 4: Week 72	—	33.220498513 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 5: Week 44	—	—	31.266295955 percentage of GAG	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 1: Week 16	—	—	—	48.562684655 percentage of GAG
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 2: Week 60	—	36.6 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 3: Week 86	23.814294737 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 6: Week 72	41.417183858 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 7: Week 120	—	126.08093356 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 8: Week 72	—	41.442593994 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 9: Week 72	—	33.736917544 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 10: Week 72	—	21.063333103 percentage of GAG	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 11: Week 60	41.011940047 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 12: Week 96	24.508878333 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 13: Week 84	11.31179 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 14: Week 62	61.047755556 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 15: Week 60	40.230919792 percentage of GAG	—	—	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 16: Week 20	—	—	38.608023285 percentage of GAG	—
Levels of Glycosaminoglycan (GAG) Concentration in Urine Participant 17: Week 8	—	—	—	39.247789595 percentage of GAG

SECONDARY outcome

Timeframe: Baseline, Week 120

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 120

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 120

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

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.

Outcome measures

Outcome data not reported

Adverse Events

Group 1

Serious events: 6 serious events

Other events: 7 other events

Deaths: 0 deaths

Group 2

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Group 3A

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Group 3B

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group 1 n=7 participants at risk 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).	Group 2 n=6 participants at risk 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).	Group 3A n=2 participants at risk 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).	Group 3B n=2 participants at risk 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).
Blood and lymphatic system disorders Leukopenia	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Gastrointestinal disorders Vomiting	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Adverse drug reaction	14.3% 1/7 • Number of events 8 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Device breakage	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Device failure	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Implant site extravasation	28.6% 2/7 • Number of events 3 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Implant site pain	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
General disorders Pyrexia	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Central nervous system infection	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Epstein-Barr virus infection	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Gastroenteritis viral	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Gastrointestinal infection	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Implant site infection	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Pharyngotonsillitis	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Postoperative wound infection	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Skin infection	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Urinary tract infection	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Infections and infestations Wound infection	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Injury, poisoning and procedural complications Incision site swelling	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Injury, poisoning and procedural complications Tooth injury	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	16.7% 1/6 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Nervous system disorders Cerebrospinal fluid leakage	28.6% 2/7 • Number of events 2 • From start of study drug administration up to follow-up (Week 276)	66.7% 4/6 • Number of events 5 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/7 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	50.0% 1/2 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	14.3% 1/7 • Number of events 1 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/6 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)	0.00% 0/2 • From start of study drug administration up to follow-up (Week 276)