Trial Outcomes & Findings for A Study to Assess the Safety and Tolerability of SOBI003 in Pediatric MPS IIIA Patients (NCT NCT03423186)

NCT ID: NCT03423186

Last Updated: 2021-11-19

Results Overview

Number of adverse events, by type and severity, from start of infusion up to 24 weeks

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

From start of first infusion up to Week 24

Results posted on

2021-11-19

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Group 1 SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Overall Study STARTED	3	3
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Assess the Safety and Tolerability of SOBI003 in Pediatric MPS IIIA Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Total n=6 Participants Total of all reporting groups
Age, Continuous	46.3 months STANDARD_DEVIATION 24.2 • n=5 Participants	29.0 months STANDARD_DEVIATION 12.2 • n=7 Participants	37.7 months STANDARD_DEVIATION 19.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of first infusion up to Week 24

Number of adverse events, by type and severity, from start of infusion up to 24 weeks

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious TEAE leading to study and/or treatment withdrawal	0 number of events	0 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any TEAE leading to death	0 number of events	0 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any adverse event	53 number of events	128 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any non-treatment emergent serious adverse event	0 number of events	1 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any treatment emergent adverse event (TEAE)	53 number of events	124 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any drug-related TEAE	27 number of events	74 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any non-serious TEAE	52 number of events	121 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious TEAE	1 number of events	3 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious drug-related TEAE	0 number of events	0 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any TEAE leading to study and/or treatment withdrawal	0 number of events	0 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any drug-related TEAE leading to study and/or treatment withdrawal	0 number of events	0 number of events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any Infusion related Reaction	17 number of events	27 number of events

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 8, 12, and 24

Population: The table report number of available pharmacokinetic (PK) samples

The observed serum concentration immediately before the start of infusion of SOBI003 (CPre-dose).

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 1	NA ng/mL Levels below LLOQ	NA ng/mL Levels below LLOQ
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 2	58.4 ng/mL Interval 33.0 to 62.2	109.0 ng/mL Interval 85.7 to 137.0
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 3	68.85 ng/mL Interval 55.2 to 82.5	135.5 ng/mL Interval 114.0 to 157.0
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 4	71.4 ng/mL Interval to 97.7 Levels below LLOQ	49.8 ng/mL Interval 31.4 to 603.0
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 8	NA ng/mL Interval to 27.0 Levels below LLOQ	25.5 ng/mL Interval to 51.0 Levels below LLOQ
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 12	33.75 ng/mL Interval 26.6 to 40.9	NA ng/mL Interval to 10.3 Levels below LLOQ
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 24	NA ng/mL Levels below LLOQ	16.4 ng/mL Interval to 90.0 Levels below LLOQ

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 8, 12, and 24

Population: Number of analysed are available samples

The observed serum concentration at the end of infusion of SOBI003 (CEnd of inf)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 1	33800 ng/mL Interval 29500.0 to 36400.0	87500 ng/mL Interval 75300.0 to 114000.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 2	34950 ng/mL Interval 33300.0 to 36600.0	108200 ng/mL Interval 99400.0 to 117000.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 3	36750 ng/mL Interval 31300.0 to 42200.0	82700 ng/mL Interval 73300.0 to 92100.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 4	35700 ng/mL Interval 16150.0 to 36600.0	77400 ng/mL Interval 71800.0 to 102000.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 8	20800 ng/mL Interval 65.5 to 36600.0	50900 ng/mL Interval 33300.0 to 68600.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 12	30500 ng/mL Interval 32.5 to 36700.0	56900 ng/mL Interval 56100.0 to 71000.0
The Observed Serum Concentration at the End of Infusion of SOBI003 Week 24	17500 ng/mL Interval 47.5 to 35400.0	93500 ng/mL Interval 69700.0 to 103000.0

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 8, 12, and 24

Population: Number of analysed are available samples

The time of the end of infusion of SOBI003 (tEnd of inf)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Time of the End of the Infusion of SOBI003 Week 1	4.57 Hours Interval 4.27 to 4.62	4.33 Hours Interval 4.02 to 4.33
The Time of the End of the Infusion of SOBI003 Week 2	4.565 Hours Interval 4.3 to 4.83	4.245 Hours Interval 4.07 to 4.42
The Time of the End of the Infusion of SOBI003 Week 3	4.28 Hours Interval 4.13 to 4.43	4.1 Hours Interval 3.98 to 4.22
The Time of the End of the Infusion of SOBI003 Week 4	4.28 Hours Interval 4.05 to 4.5	4.42 Hours Interval 4.27 to 4.9
The Time of the End of the Infusion of SOBI003 Week 8	4.85 Hours Interval 4.42 to 6.58	8.17 Hours Interval 8.17 to 8.17
The Time of the End of the Infusion of SOBI003 Week 12	4.23 Hours Interval 4.1 to 6.42	6.83 Hours Interval 5.08 to 7.03
The Time of the End of the Infusion of SOBI003 Week 24	4.45 Hours Interval 4.08 to 4.53	4.75 Hours Interval 4.47 to 5.57

SECONDARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Weeks 1, 4, 12, and 24

Population: Samples was taken centrally and/or peripherally.

The Maximum Observed Serum Concentration of SOBI003 (Cmax)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Maximum Observed Serum Concentration of SOBI003 Week 4	35700 ng/mL Interval 16150.0 to 36600.0	77400 ng/mL Interval 71800.0 to 102000.0
The Maximum Observed Serum Concentration of SOBI003 Week 12	20800 ng/mL Interval 65.5 to 36400.0	56900 ng/mL Interval 56100.0 to 71000.0
The Maximum Observed Serum Concentration of SOBI003 Week 24	17500 ng/mL Interval 47.5 to 35400.0	93500 ng/mL Interval 69700.0 to 103000.0
The Maximum Observed Serum Concentration of SOBI003 Week 1	33800 ng/mL Interval 29500.0 to 36400.0	87500 ng/mL Interval 75300.0 to 114000.0

SECONDARY outcome

Timeframe: Weeks 1, 4, 12, and 24

The time after start of infusion at which the maximum serum concentration is observed (tmax)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 1	4.57 Hours Interval 4.27 to 4.62	4.33 Hours Interval 4.02 to 4.33
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 4	4.28 Hours Interval 4.05 to 4.5	4.42 Hours Interval 4.27 to 4.9
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 12	4.23 Hours Interval 4.1 to 6.42	6.83 Hours Interval 5.08 to 7.03
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 24	4.45 Hours Interval 4.08 to 4.53	4.75 Hours Interval 4.47 to 5.57

SECONDARY outcome

Timeframe: Weeks 1, 4, 12, and 24

The minimum observed serum concentration of SOBI003 (CTrough)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Minimum Observed Serum Concentration of SOBI003 Week 12	26.2 ng/mL Interval 17.0 to 32.5	NA ng/mL Interval to 29.7 Levels below LLOQ
The Minimum Observed Serum Concentration of SOBI003 Week 24	44.8 ng/mL Interval to 47.5 Levels below LLOQ	NA ng/mL Interval 14.6 to 9010.0 Levels below LLOQ
The Minimum Observed Serum Concentration of SOBI003 Week 1	NA ng/mL Interval to 2010.0 Levels below LLOQ	NA ng/mL Levels below LLOQ
The Minimum Observed Serum Concentration of SOBI003 Week 4	28.9 ng/mL Interval to 61.3 Levels below LLOQ	115 ng/mL Interval 20.8 to 7730.0

SECONDARY outcome

Timeframe: Weeks 1, 4, 12, and 24

Clearance (CL) of SOBI003

Outcome measures

Outcome measures
Measure	Dose Group 1 n=2 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=2 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Clearance Week 4	8.1 (mL/h)/kg Interval 8.0 to 8.2	12.75 (mL/h)/kg Interval 12.4 to 13.1
Clearance Week 12	9.5 (mL/h)/kg Interval 7.8 to 11.2	13.45 (mL/h)/kg Interval 12.1 to 14.8
Clearance Week 24	19.5 (mL/h)/kg Interval 10.2 to 28.8	10.4 (mL/h)/kg Interval 9.9 to 10.9
Clearance Week 1	10.4 (mL/h)/kg Interval 9.7 to 11.1	12.8 (mL/h)/kg Interval 12.0 to 13.6

SECONDARY outcome

Timeframe: 0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 1, 4,12, and 24

Population: Number of analysed are available samples

Area under the serum concentration-time curve from time 0 to 168 hours (AUC 0-168h)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours Week 1	290044.5 h*ng/mL Interval 275152.0 to 304937.0	834411 h*ng/mL Interval 737687.0 to 2492658.0
Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours Week 4	369915.5 h*ng/mL Interval 365435.0 to 374396.0	789106.5 h*ng/mL Interval 761760.0 to 816453.0
Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours Week 12	324999.5 h*ng/mL Interval 267722.0 to 382277.0	749864 h*ng/mL Interval 674188.0 to 828540.0
Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours Week 24	198973 h*ng/mL Interval 104009.0 to 293937.0	961516.5 h*ng/mL Interval 915941.0 to 1007092.0

SECONDARY outcome

Timeframe: Weeks 1, 4, 12, and 24

The half-life of SOBI003 in serum (T1/2)

Outcome measures

Outcome measures
Measure	Dose Group 1 n=2 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=2 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
The Half-life Week 1	19.8 Hours Interval 5.4 to 34.2	22.75 Hours Interval 5.8 to 39.7
The Half-life Week 4	34.3 Hours Interval 29.7 to 38.9	7.65 Hours Interval 6.3 to 9.0
The Half-life Week 12	40.95 Hours Interval 34.4 to 47.5	10.75 Hours Interval 8.8 to 12.7
The Half-life Week 24	20.85 Hours Interval 9.3 to 32.4	15.95 Hours Interval 6.0 to 25.9

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: Number of analysed are available samples

SOBI003 concentration in cerebrospinal fluid

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
SOBI003 Concentration in Cerebrospinal Fluid Week 12	NA mg/L Levels below LLOQ	17.8 mg/L Interval 17.8 to 17.8
SOBI003 Concentration in Cerebrospinal Fluid Week 24	NA mg/L Levels below LLOQ	47.2 mg/L Interval 12.2 to 64.6

SECONDARY outcome

Timeframe: Weeks 2,4,8,12 and 24

Number of patients in each dose group having anti-drug antibodies in serum

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Number of Patients Having Anti-drug Antibodies in Serum Weeks 2	1 Participants	1 Participants
Number of Patients Having Anti-drug Antibodies in Serum Weeks 4	2 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Serum Weeks 8	3 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Serum Weeks 12	3 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Serum Weeks 24	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Weeks 12 and 24

Percent of patients having anti-drug antibodies in cerebrospinal fluid

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Patients Having Anti-drug Antibodies in Cerebrospinal Fluid Week 12	33.3 percent of participants in dose group	66.7 percent of participants in dose group
Patients Having Anti-drug Antibodies in Cerebrospinal Fluid Week 24	66.7 percent of participants in dose group	100 percent of participants in dose group

SECONDARY outcome

Timeframe: Baseline, weeks 12, and 24

Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid Week 12	-5.4 percent change Interval -33.0 to 7.7	-52.8 percent change Interval -64.6 to -28.4
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid Week 24	-17.5 percent change Interval -26.5 to -14.7	-50.9 percent change Interval -59.4 to -21.2

SECONDARY outcome

Timeframe: Weeks 2, 3, 4, 8, 12 and 24

Change from baseline in Heparan sulfate levels in serum

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Heparan Sulfate Levels in Serum Week 12	-1.8170 mg/L Interval -2.131 to -1.597	-1.8340 mg/L Interval -3.729 to -1.722
Change From Baseline in Heparan Sulfate Levels in Serum Week 24	-1.7480 mg/L Interval -2.207 to -1.657	-1.8310 mg/L Interval -3.722 to -1.818
Change From Baseline in Heparan Sulfate Levels in Serum Week 2	-1.8070 mg/L Interval -1.891 to -0.66	-1.7460 mg/L Interval -3.409 to -1.705
Change From Baseline in Heparan Sulfate Levels in Serum Week 3	-1.22 mg/L Interval -2.006 to -0.22	-1.9190 mg/L Interval -3.576 to -1.856
Change From Baseline in Heparan Sulfate Levels in Serum Week 4	-1.9040 mg/L Interval -2.083 to -1.85	-1.9229 mg/L Interval -3.77 to -1.268
Change From Baseline in Heparan Sulfate Levels in Serum Week 8	-2.1030 mg/L Interval -2.21 to -1.615	-1.8290 mg/L Interval -3.73 to -1.772

SECONDARY outcome

Timeframe: Weeks 2, 3, 4, 8, 12 and 24

Change from baseline in Heparan sulfate levels in urine

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 2	-456.2 g/mol Interval -496.1 to -298.0	-561.1 g/mol Interval -592.1 to -231.9
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 3	-494.67 g/mol Interval -592.1 to -390.0	-597.4 g/mol Interval -618.8 to -309.3
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 4	-498.53 g/mol Interval -575.8 to -422.79	-503.465 g/mol Interval -672.17 to -334.76
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 12	-534.1 g/mol Interval -540.71 to -442.33	-640.2 g/mol Interval -668.83 to -326.13
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 24	-421.98 g/mol Interval -557.33 to -258.1	-695.9 g/mol Interval -698.03 to -348.05
Change From Baseline in Heparan Sulfate Levels in Urine Weeks 8	-474.7 g/mol Interval -542.22 to -460.95	-666.81 g/mol Interval -672.42 to -341.7

SECONDARY outcome

Timeframe: Week 24

Quotient between age equivalent score and age, 0 - 100%, where high values are desirable. The age equivalent score represent the age of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Neurocognitive Development Quotient	-8.7 unitless Interval -11.2 to -4.9	-15.68 unitless Interval -53.3 to 4.1

SECONDARY outcome

Timeframe: Week 24

The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Age-equivalence Score	-1.0 Months Interval -4.0 to 1.0	-3.0 Months Interval -6.0 to 6.0

SECONDARY outcome

Timeframe: Week 24

The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90. The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Age-equivalence Score as Assessed by VABS-II	1.0 Months Interval -9.0 to 2.0	0.0 Months Interval -3.0 to 24.0

SECONDARY outcome

Timeframe: Week 24

Grey matter contains most of the brain's neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, and sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control. The gray matter volume will be measured by volumetric magnetic resonance imaging (MRI).

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Gray Matter Volume	10.858 mL Interval -6.22 to 42.27	39.129 mL Interval -33.28 to 111.53

SECONDARY outcome

Timeframe: Week 24

Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Lower scores indicate better functioning. Min score = 0, and max score = 144.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score	-9.3 Units on a scale Standard Deviation 15.52	-7.3 Units on a scale Standard Deviation 14.9

SECONDARY outcome

Timeframe: Week 24

Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The measure includes a scale, from where the categorical score "4", "3", "2", "1", and "0" was reversed and linearly transformed to a 0-100 scale to 4=0, 3=25, 2=50, 1=75 and 0=100, where 100 = minimum and 0 = maximum. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=2 Participants SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
Change From Baseline in PedsQL™ Family Impact Module Total Score	-9.77 Units on a scale Standard Deviation 19.05	1.3 Units on a scale Standard Deviation 3.11

Adverse Events

Dose Group 1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Group 2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Group 1 n=3 participants at risk SOBI003 dose 3 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion	Dose Group 2 n=3 participants at risk SOBI003 dose 10 mg/kg once weekly for 24 weeks SOBI003: Weekly i.v.infusion
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Device related infestations	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.	33.3% 1/3 • Number of events 1 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Endocarditis	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.	33.3% 1/3 • Number of events 1 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Pneumonia	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.	33.3% 1/3 • Number of events 1 • The period for recording adverse events, including Serious Adverse Events (SAEs), began upon receiving the first dose of SOBI003 and ended at completion of the week 24 visit. In addition SAEs was reported from the time for signing the informed consent form until 28 days past the last dose of SOBI003.

Other adverse events

Additional Information

Anders Bröijersén, Medical Director

Swedish Orphan Biovitrum AB

Phone: +46 8 697 20 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place