Trial Outcomes & Findings for Safety, Tolerability, Ascending Dose and Dose Frequency Study of rhHNS Via an IDDD in MPS IIIA Patients (NCT NCT01155778)

Last Updated: 2021-06-14

Results Overview

An adverse event (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. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as all adverse events (AEs) from the time of the surgery for IDDD implantation to the last follow up contact, 30 (±7) days after the end of study (EOS) procedures.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Baseline to week 30 (follow-up)

Results posted on

2021-06-14

Participant Flow

Study enrolled 12 participants and 4 participants were included in each of the 3 dose groups.

Participant milestones

Participant milestones
Measure	HGT-1410 10 mg HGT-1410/rhHNS 10 milligram (mg) monthly via an intrathecal drug delivery device (IDDD) (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Overall Study STARTED	4	4	4
Overall Study COMPLETED	4	4	4
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, Ascending Dose and Dose Frequency Study of rhHNS Via an IDDD in MPS IIIA Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.	Total n=12 Participants Total of all reporting groups
Age, Continuous	9.15 years STANDARD_DEVIATION 4.7 • n=5 Participants	9.07 years STANDARD_DEVIATION 9.8 • n=7 Participants	10.64 years STANDARD_DEVIATION 8.7 • n=5 Participants	9.618 years STANDARD_DEVIATION 7.2941 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to week 30 (follow-up)

Population: Safety population was defined as all enrolled participants who received at least 1 dose (full or partial) of study drug.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Number of Treatment Emergent Serious Adverse Events (SAE)	5 events	3 events	2 events

PRIMARY outcome

Timeframe: Baseline to week 30 (follow-up)

Population: Safety population.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Number of Treatment Emergent Adverse Events (TEAE)	71 events	42 events	55 events

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Intent to treat (ITT) population was defined as all enrolled participants who received at least 1 dose (full or partial) of study drug.

Participants with positive, negative and missing status were reported.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Negative (Baseline)	4 participants	4 participants	4 participants
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Positive (Baseline)	0 participants	0 participants	0 participants
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Missing (Baseline)	0 participants	0 participants	0 participants
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Negative (Week 26)	1 participants	1 participants	2 participants
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Positive (Week 26)	0 participants	0 participants	0 participants
Summary of Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Missing (Week 26)	3 participants	3 participants	2 participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: ITT population

Participants with positive, negative and missing status were reported.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Negative (Week 26)	1 participants	2 participants	2 participants
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Negative (Baseline)	4 participants	3 participants	3 participants
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Positive (Baseline)	0 participants	1 participants	1 participants
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Missing (Baseline)	0 participants	0 participants	0 participants
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Positive (Week 26)	2 participants	0 participants	0 participants
Summary of Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) Dose Group Missing (Week 26)	1 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: Week 26

Population: ITT population.

Participants with IDDD failures were reported.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Number of Participants With Intrathecal Drug Device (IDDD) Failures at Week 26	3 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, Week 22

Population: ITT population. Here, n = participants evaluable for specified category for each arm, respectively.

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers. This measure consists of a series of developmental play tasks. Raw scores of successfully completed items are converted to scale scores and to composite scores. The mean composite score is 100 and the standard deviation (SD) is 15.Higher scores are indicative of decreased development. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and is an alternative to BSID-III. BSID-III DQ score was based on the Cognitive domain. The DQ score was calculated from the data obtained from either BSID-III/KABC-II mental age equivalent of the child in months divided by the calendar age in months (multiplied by 100 to give percentage points).

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID III) and Kaufman Assessment Battery for Children Second Edition (KABC II) at Week 22 Baseline (n= 2, 4, 4)	51.91 units on a scale Standard Deviation 27.292	43.24 units on a scale Standard Deviation 23.112	51.87 units on a scale Standard Deviation 36.095
Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID III) and Kaufman Assessment Battery for Children Second Edition (KABC II) at Week 22 Change at Week 22 (n= 2, 4, 4)	-13.6 units on a scale Standard Deviation 8.886	-0.89 units on a scale Standard Deviation 4.341	-4.91 units on a scale Standard Deviation 7.769

SECONDARY outcome

Timeframe: Baseline, Week 22, Week 26

Population: ITT population. Here, n = participants evaluable for specified category for each arm, respectively.

FPSS is a sanfilippo-specific disability assessment which assesses motor function, expressive/speech language, and cognitive function on a 0 to 3 point scale. A score of 3 points is assigned for normal function, 2 points for beginning of regression, 1 point for severe level of regression, and 0 points for lost skills. The total disability score (TDS) is the average (0-3) of the motor skills (MS), speech abilities (SA), and cognitive function (CF) scores. Lower scores indicate developmental regression.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) MS: Baseline (n= 4, 3, 4)	2.5 units on a scale Standard Deviation 0.58	3 units on a scale Standard Deviation 0	3 units on a scale Standard Deviation 0
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) MS: Change at Week 22 (n= 4, 3, 4)	0.3 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) MS: Change at Week 26/EOS (n=2,2,3)	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) SA: Baseline (n= 4, 3, 4)	2 units on a scale Standard Deviation 0.82	2 units on a scale Standard Deviation 0	2 units on a scale Standard Deviation 0.82
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) SA: Change at Week 22 (n= 4, 3, 4)	-0.5 units on a scale Standard Deviation 0.58	0.3 units on a scale Standard Deviation 0.58	0.3 units on a scale Standard Deviation 0.5
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) SA: Change at Week 26/EOS (n= 2, 2, 3)	-0.5 units on a scale Standard Deviation 0.71	0 units on a scale Standard Deviation 0	0.3 units on a scale Standard Deviation 0.58
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) CF: Baseline (n= 4, 3, 4)	2.3 units on a scale Standard Deviation 0.5	0.5 units on a scale Standard Deviation 0.58	2.8 units on a scale Standard Deviation 0.5
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) CF: Change at Week 22 (n= 4, 3, 4)	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) CF: Change at Week 26/EOS (n= 2, 2, 3)	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) TDS: Baseline (n= 4, 3, 4)	2.25 units on a scale Standard Deviation 0.569	2.44 units on a scale Standard Deviation 0.192	2.58 units on a scale Standard Deviation 0.319
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) TDS: Change at Week 22 (n= 4, 3, 4)	-0.08 units on a scale Standard Deviation 0.319	0.11 units on a scale Standard Deviation 0.192	0.08 units on a scale Standard Deviation 0.167
Change From Baseline in Four Point Scoring System/Total Disability Score (FPSS/TDS) at Week 22 and Week 26 (EOS) TDS: Change at Week 26/EOS (n= 2, 2, 3)	-0.17 units on a scale Standard Deviation 0.236	0 units on a scale Standard Deviation 0	0.11 units on a scale Standard Deviation 0.192

SECONDARY outcome

Timeframe: Baseline, Week 22, Week 26/EOS

Population: ITT population. Here, n = participants evaluable for specified category for each arm, respectively.

SBRS a parent-scored behavioral inventory measuring: comprehensive language skills, expressive language skills, tantrums, mood and emotions, and other behaviors not otherwise classified. Subscale items are scored 0=Never, 1=Occasionally(5-10%), 2=Sometimes (25%), 3=About half the time, 4=Often(75%), 5=Almost always (90%), 6=Always. Summary scores are the sum of responses within a given domain. Higher values = undesirable behavior. Total score range listed below with the abbreviations. Current Communication (CC)(0-42), Past Communication (PC)(0-42), Orality (0-36), Body Movements (BM)(0-30), Interaction With Objects (IWO)(0-24), Activity And Routines (AAR)(0-36), Emotional Function (EF)(0-18), Safety-consciousness (SC)(0-18), Fearfulness (0-36), Social Interaction (SI)(0-36), Eye Contact (EC)(0-18), Emotional Engagement (EE)(0-18), Comfort Seeking (CS)(0-30), Attention (0-18), Self-control/Compliance (SCC)(0-18), Mood, Anger/Aggression (MAA)(0-42), Self-gratification (SG)(0-24).

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CC: Baseline (n= 4, 4, 2)	8.0 units on a scale Standard Deviation 5.48	6.3 units on a scale Standard Deviation 6.85	10.0 units on a scale Standard Deviation 5.66
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CC: Change at Week 22 (n= 4, 4, 2)	5.0 units on a scale Standard Deviation 13.44	-0.3 units on a scale Standard Deviation 1.26	1.5 units on a scale Standard Deviation 2.12
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CC: Change at Week 26/EOS (n= 3, 2, 2)	1.3 units on a scale Standard Deviation 12.5	-1.0 units on a scale Standard Deviation 1.41	1.5 units on a scale Standard Deviation 2.12
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) PC: Baseline (n= 3, 2, 4)	7.3 units on a scale Standard Deviation 6.03	8.5 units on a scale Standard Deviation 12.02	11.0 units on a scale Standard Deviation 11.37
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) PC: Change at Week 22 (n= 1, 0, 1)	-8.0 units on a scale Standard Deviation NA Not applicable (NA) signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) PC: Change at Week 26/EOS (n= 0, 0, 0)	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Orality: Baseline (n= 2, 3, 3)	7.0 units on a scale Standard Deviation 9.9	10.3 units on a scale Standard Deviation 2.08	17.3 units on a scale Standard Deviation 10.26
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Orality: Change at Week 22 (n= 2, 3, 1)	2.0 units on a scale Standard Deviation 2.83	6.0 units on a scale Standard Deviation 5.29	4.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Orality: Change at Week 26/EOS (n= 1, 1, 1)	0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	5 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	4 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SG: Baseline (n= 4, 3, 4)	0.5 units on a scale Standard Deviation 1.0	0.3 units on a scale Standard Deviation 0.58	4.5 units on a scale Standard Deviation 5.26
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) BM: Baseline (n= 4, 4, 2)	5.0 units on a scale Standard Deviation 4.55	2.5 units on a scale Standard Deviation 2.08	12.0 units on a scale Standard Deviation 2.83
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) BM: Change at Week 22 (n= 3, 4, 2)	2.3 units on a scale Standard Deviation 3.51	2 units on a scale Standard Deviation 2.45	-2.0 units on a scale Standard Deviation 2.83
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) BM: Change at Week 26/EOS (n= 3, 2, 2)	0.3 units on a scale Standard Deviation 1.53	0 units on a scale Standard Deviation 0	-2.0 units on a scale Standard Deviation 2.83
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) IWO: Baseline (n= 4, 3, 4)	4.5 units on a scale Standard Deviation 3.11	10.3 units on a scale Standard Deviation 2.08	8.5 units on a scale Standard Deviation 7.9
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) IWO: Change at Week 22 (n= 4, 3, 3)	3.3 units on a scale Standard Deviation 4.27	-2.0 units on a scale Standard Deviation 4.58	-2.0 units on a scale Standard Deviation 3.46
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) IWO: Change at Week 26/EOS (n= 2, 1, 3)	1.0 units on a scale Standard Deviation 1.41	-1.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	-2.0 units on a scale Standard Deviation 3.46
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SG: Change at Week 22 (n= 3, 3, 4)	-0.7 units on a scale Standard Deviation 1.15	2.0 units on a scale Standard Deviation 1.0	-1.0 units on a scale Standard Deviation 4.08
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) AAR: Baseline (n= 1, 3, 4)	6.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	14.3 units on a scale Standard Deviation 3.06	12.3 units on a scale Standard Deviation 9.46
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) AAR: Change at Week 22 (n= 1, 3, 4)	8.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	0.7 units on a scale Standard Deviation 0.58	-1.3 units on a scale Standard Deviation 6.08
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) AAR: Change at Week 26/EOS (n= 0, 1, 3)	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	1.7 units on a scale Standard Deviation 2.08
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EF: Baseline (n= 3, 4, 4)	2.0 units on a scale Standard Deviation 3.46	2.5 units on a scale Standard Deviation 3.11	7.5 units on a scale Standard Deviation 5.0
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EF: Change at Week 22 (n= 3, 4, 4)	2.0 units on a scale Standard Deviation 3.46	2.5 units on a scale Standard Deviation 3.11	7.5 units on a scale Standard Deviation 5.0
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EF: Change at Week 26/EOS (n= 2, 2, 3)	5.0 units on a scale Standard Deviation 1.41	0.5 units on a scale Standard Deviation 0.71	-1.31 units on a scale Standard Deviation 3.06
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SC: Baseline (n= 4, 4, 4)	7.8 units on a scale Standard Deviation 5.44	9.5 units on a scale Standard Deviation 1.91	11.5 units on a scale Standard Deviation 7.9
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SC: Change at Week 22 (n= 4, 4, 4)	0.5 units on a scale Standard Deviation 1.0	1.8 units on a scale Standard Deviation 5.74	-0.8 units on a scale Standard Deviation 2.5
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SC: Change at Week 26/EOS (n= 3, 2, 3)	-1.0 units on a scale Standard Deviation 2.65	-3.0 units on a scale Standard Deviation 2.83	-1.0 units on a scale Standard Deviation 3.0
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Fearfulness: Baseline (n= 3, 3, 3)	7.0 units on a scale Standard Deviation 7.81	10.3 units on a scale Standard Deviation 8.74	11.0 units on a scale Standard Deviation 6.08
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Fearfulness: Change at Week 22 (n= 3, 3, 3)	2.7 units on a scale Standard Deviation 1.15	-1.0 units on a scale Standard Deviation 5.2	2.0 units on a scale Standard Deviation 1.73
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Fearfulness: Change at Week 26/EOS (n= 2, 1, 3)	2.5 units on a scale Standard Deviation 2.12	-5 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	2.3 units on a scale Standard Deviation 1.53
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SI: Baseline (n= 4, 4, 4)	11.0 units on a scale Standard Deviation 3.37	12.5 units on a scale Standard Deviation 2.38	14.5 units on a scale Standard Deviation 6.76
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SI: Change at Week 22 (n= 4, 3, 4)	3.0 units on a scale Standard Deviation 4.76	0.3 units on a scale Standard Deviation 4.04	-0.5 units on a scale Standard Deviation 3.7
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SI: Change at Week 26/EOS (n= 3, 2, 3)	0 units on a scale Standard Deviation 8.0	-3.5 units on a scale Standard Deviation 4.95	-0.7 units on a scale Standard Deviation 4.62
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EC: Baseline (n= 4, 4, 3)	2.8 units on a scale Standard Deviation 3.59	5.5 units on a scale Standard Deviation 3.7	6.7 units on a scale Standard Deviation 5.77
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EC: Change at Week 22 (n= 4, 4, 3)	1.5 units on a scale Standard Deviation 1.73	0 units on a scale Standard Deviation 3.27	-1.0 units on a scale Standard Deviation 2.65
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EC: Change at Week 26/EOS (n= 3, 2, 3)	0.3 units on a scale Standard Deviation 0.58	-2.0 units on a scale Standard Deviation 2.83	-0.7 units on a scale Standard Deviation 3.06
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EE: Baseline (n= 2, 4, 4)	8.5 units on a scale Standard Deviation 4.95	7.3 units on a scale Standard Deviation 1.71	8.3 units on a scale Standard Deviation 3.3
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EE: Change at Week 22 (n= 1, 4, 4)	2.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	-0.5 units on a scale Standard Deviation 1.29	-0.8 units on a scale Standard Deviation 2.87
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) EE: Change at Week 26/EOS (n= 0, 2, 3)	NA units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	-1.0 units on a scale Standard Deviation 1.41	0.7 units on a scale Standard Deviation 1.15
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CS: Baseline (n= 4, 3, 4)	10.3 units on a scale Standard Deviation 5.32	10.3 units on a scale Standard Deviation 3.06	16.5 units on a scale Standard Deviation 6.56
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CS: Change at Week 22 (n= 3, 3, 3)	1.7 units on a scale Standard Deviation 4.73	-1.7 units on a scale Standard Deviation 3.06	-2.3 units on a scale Standard Deviation 3.21
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) CS: Change at Week 26/EOS (n= 2, 1, 3)	0 units on a scale Standard Deviation 1.41	-1.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	-2.3 units on a scale Standard Deviation 3.21
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Attention: Baseline (n= 4, 4, 4)	8.3 units on a scale Standard Deviation 4.65	8.8 units on a scale Standard Deviation 1.26	10.5 units on a scale Standard Deviation 7.72
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Attention: Change at Week 22 (n= 4, 4, 4)	1.0 units on a scale Standard Deviation 3.16	2.5 units on a scale Standard Deviation 2.38	2.3 units on a scale Standard Deviation 1.71
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) Attention: Change at Week 26/EOS (n= 2, 2, 3)	1.5 units on a scale Standard Deviation 2.12	0.5 units on a scale Standard Deviation 0.71	3.3 units on a scale Standard Deviation 1.15
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SCC: Baseline (n= 4, 4, 4)	8.0 units on a scale Standard Deviation 4.97	7.3 units on a scale Standard Deviation 2.22	10.0 units on a scale Standard Deviation 7.3
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SCC: Change at Week 22 (n= 3, 4, 4)	0.3 units on a scale Standard Deviation 4.51	3.3 units on a scale Standard Deviation 3.2	2.0 units on a scale Standard Deviation 1.83
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SCC: Change at Week 26/EOS (n= 3, 2, 3)	0.7 units on a scale Standard Deviation 4.04	0.5 units on a scale Standard Deviation 0.71	2.7 units on a scale Standard Deviation 1.53
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) MAA: Baseline (n= 4, 3, 4)	5.3 units on a scale Standard Deviation 4.11	9.7 units on a scale Standard Deviation 3.51	17.3 units on a scale Standard Deviation 15.65
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) MAA: Change at Week 22 (n= 2, 3, 4)	5.5 units on a scale Standard Deviation 7.78	3.3 units on a scale Standard Deviation 5.13	-0.3 units on a scale Standard Deviation 2.5
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) MAA: Change at Week 26/EOS (n= 3, 1, 3)	1.7 units on a scale Standard Deviation 3.06	4.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	-0.7 units on a scale Standard Deviation 2.89
Change From Baseline in Sanfilippo Behavioral Rating Scale (SBRS) at Week 22 and Week 26 (EOS) SG: Change at Week 26/EOS (n= 3, 1, 3)	0.3 units on a scale Standard Deviation 0.58	1.0 units on a scale Standard Deviation NA NA signifies standard deviation not reported as there was only 1 evaluable participant and data was not available for the specific measure	1.0 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline, Week 22

Population: ITT population. Here, n = participants evaluable for specified category for each arm, respectively.

VABS-II measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measures 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other four domains). Scoring is 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The raw scores will be converted to domain standard scores (mean 100, SD 15). Higher scores indicate undesirable behavior. The Overall DQ score was calculated from the mean age-equivalent score obtained by averaging out the age equivalent scores for all the sub-domains except for Gross and Fine motor skills.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Change From Baseline in Developmental Quotient (DQ) Using Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Week 22 Baseline (n= 4, 4, 4)	44.78 units on a scale Standard Deviation 24.747	47.24 units on a scale Standard Deviation 26.612	47.71 units on a scale Standard Deviation 33.687
Change From Baseline in Developmental Quotient (DQ) Using Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Week 22 Change at Week 22 (n= 2, 2, 2)	-11.38 units on a scale Standard Deviation 12.478	-23.96 units on a scale Standard Deviation 10.014	-10.18 units on a scale Standard Deviation 13.333

SECONDARY outcome

Population: ITT population. Here, n = participants evaluable for specified category for each arm, respectively.

ABR assessments were to be conducted under anesthesia and measured the electrical response evoked by acoustic stimuli as sound is processed along the auditory pathway. Data for change from baseline in ABR square-root transformed amplitude (STA) by left and right ear were reported.

Outcome measures

Outcome measures
Measure	HGT-1410 10 mg n=4 Participants HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 Participants HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 Participants HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave I: Week 22 (n= 2, 3, 3)	-0.193 square-root transformed(amplitude [mcV]) Standard Deviation 0.0535	-0.172 square-root transformed(amplitude [mcV]) Standard Deviation 0.1615	-0.044 square-root transformed(amplitude [mcV]) Standard Deviation 0.2298
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave III: Baseline (n= 2, 3, 3)	0.566 square-root transformed(amplitude [mcV]) Standard Deviation 0.1374	0.575 square-root transformed(amplitude [mcV]) Standard Deviation 0.171	0.479 square-root transformed(amplitude [mcV]) Standard Deviation 0.1274
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave III: Week 22 (n= 2, 3, 2)	-0.038 square-root transformed(amplitude [mcV]) Standard Deviation 0.0838	-0.122 square-root transformed(amplitude [mcV]) Standard Deviation 0.0927	-0.211 square-root transformed(amplitude [mcV]) Standard Deviation 0.2317
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave V: Baseline (n= 2, 3, 3)	0.775 square-root transformed(amplitude [mcV]) Standard Deviation 0.2599	0.678 square-root transformed(amplitude [mcV]) Standard Deviation 0.1022	0.557 square-root transformed(amplitude [mcV]) Standard Deviation 0.0954
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave V: Week 22 (n= 2, 3, 3)	-0.18 square-root transformed(amplitude [mcV]) Standard Deviation 0.2183	-0.069 square-root transformed(amplitude [mcV]) Standard Deviation 0.1049	-0.197 square-root transformed(amplitude [mcV]) Standard Deviation 0.2547
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave I: Baseline (n= 2, 3, 4)	0.632 square-root transformed(amplitude [mcV]) Standard Deviation 0.0224	0.655 square-root transformed(amplitude [mcV]) Standard Deviation 0.1437	0.499 square-root transformed(amplitude [mcV]) Standard Deviation 0.133
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave III: Baseline (n= 2, 3, 4)	0.456 square-root transformed(amplitude [mcV]) Standard Deviation 0.1162	0.601 square-root transformed(amplitude [mcV]) Standard Deviation 0.1508	0.45 square-root transformed(amplitude [mcV]) Standard Deviation 0.1131
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave III: Week 22 (n= 2, 3, 3)	0.057 square-root transformed(amplitude [mcV]) Standard Deviation 0.068	-0.085 square-root transformed(amplitude [mcV]) Standard Deviation 0.1798	0.015 square-root transformed(amplitude [mcV]) Standard Deviation 0.0422
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave V: Baseline (n= 2, 3, 4)	0.709 square-root transformed(amplitude [mcV]) Standard Deviation 0.1896	0.692 square-root transformed(amplitude [mcV]) Standard Deviation 0.0873	0.518 square-root transformed(amplitude [mcV]) Standard Deviation 0.1488
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave V: Week 22 (n= 2, 3, 4)	-0.084 square-root transformed(amplitude [mcV]) Standard Deviation 0.167	-0.019 square-root transformed(amplitude [mcV]) Standard Deviation 0.0956	-0.004 square-root transformed(amplitude [mcV]) Standard Deviation 0.0832
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-RE, Wave I: Baseline (n= 2, 3, 3)	0.7 square-root transformed(amplitude [mcV]) Standard Deviation 0.0303	0.644 square-root transformed(amplitude [mcV]) Standard Deviation 0.0896	0.507 square-root transformed(amplitude [mcV]) Standard Deviation 0.0933
Change From Baseline in Auditory Brainstem Response (ABR) at Week 22: Square-root Transformed Amplitude STA-LE, Wave I: Week 22 (n= 2, 3, 3)	-0.101 square-root transformed(amplitude [mcV]) Standard Deviation 0.1638	-0.028 square-root transformed(amplitude [mcV]) Standard Deviation 0.1961	0.006 square-root transformed(amplitude [mcV]) Standard Deviation 0.1365

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HGT-1410 10 mg n=4 participants at risk HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 participants at risk HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 participants at risk HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Surgical and medical procedures Medical device change	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)
General disorders Device breakage	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Device component issue	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Device failure	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Postoperative wound infection	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Viral infection	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)

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 Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	HGT-1410 10 mg n=4 participants at risk HGT-1410/rhHNS 10 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 45 mg n=4 participants at risk HGT-1410/rhHNS 45 mg monthly via an IDDD (every 28 \[±7 days\]) for a total of 6 months.	HGT-1410 90 mg n=4 participants at risk HGT-1410/rhHNS 45 mg dose every 14 \[±2 days\] for a monthly total dose of 90 mg via an IDDD for 6 months.
Ear and labyrinth disorders Tympanic membrane disorder	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Abnormal faeces	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Constipation	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Number of events 5 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 3 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Regurgitation	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Gastrointestinal disorders Vomiting	50.0% 2/4 • Number of events 6 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 2 • Baseline to Week 30 (follow-up)
General disorders Administration site pain	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Catheter site erythema	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Device breakage	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Device failure	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Fatigue	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
General disorders Implant site swelling	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Irritability	50.0% 2/4 • Number of events 3 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Malaise	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Medical device complication	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
General disorders Pain	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
General disorders Pyrexia	75.0% 3/4 • Number of events 5 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 7 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)
Immune system disorders Seasonal allergy	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Candida nappy rash	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Gastroenteritis	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Nasopharyngitis	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Infections and infestations Otitis externa	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Infections and infestations Otitis media	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Post procedural infection	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Postoperative wound infection	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)
Infections and infestations Proteus infection	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Rhinitis	50.0% 2/4 • Number of events 3 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 4 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 2 • Baseline to Week 30 (follow-up)
Infections and infestations Upper respiratory tract infection	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Viral rash	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Fall	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Open wound	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Post procedural discomfort	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Procedural pain	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Procedural site reaction	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Injury, poisoning and procedural complications Procedural vomiting	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Investigations CSF protein increased	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Investigations CSF white blood cell count increased	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Investigations Haemoglobin decreased	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Investigations Lymphocyte count increased	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Investigations Neutrophil count decreased	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Investigations Norovirus test positive	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Investigations Serum ferritin decreased	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Musculoskeletal and connective tissue disorders Trigger finger	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Cauda equina syndrome	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 7 • Baseline to Week 30 (follow-up)
Nervous system disorders Cognitive disorder	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Crying	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Drooling	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Headache	50.0% 2/4 • Number of events 4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 11 • Baseline to Week 30 (follow-up)
Nervous system disorders Memory impairment	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Motor dysfunction	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Paraesthesia	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Nervous system disorders Psychomotor hyperactivity	0.00% 0/4 • Baseline to Week 30 (follow-up)	50.0% 2/4 • Number of events 2 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Nervous system disorders Syncope	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Psychiatric disorders Anxiety	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Psychiatric disorders Depressed mood	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Psychiatric disorders Restlessness	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Renal and urinary disorders Micturition urgency	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 7 • Baseline to Week 30 (follow-up)
Renal and urinary disorders Urinary incontinence	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Reproductive system and breast disorders Labia enlarged	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Reproductive system and breast disorders Penile adhesion	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 2 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Surgical and medical procedures Infection prophylaxis	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Vascular disorders Hypertension	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)
Vascular disorders Pallor	0.00% 0/4 • Baseline to Week 30 (follow-up)	25.0% 1/4 • Number of events 1 • Baseline to Week 30 (follow-up)	0.00% 0/4 • Baseline to Week 30 (follow-up)