Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients (NCT NCT03811028)

NCT ID: NCT03811028

Last Updated: 2022-02-25

Results Overview

Number of adverse events, by type and severity, from week 25 up to week 104

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

From infusion week 25 up to week 104

Results posted on

2022-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Group 1 SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 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, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Total n=6 Participants Total of all reporting groups
Age, Continuous	52.0 months STANDARD_DEVIATION 23.8 • n=5 Participants	34.7 months STANDARD_DEVIATION 12.7 • n=7 Participants	43.3 months STANDARD_DEVIATION 19.5 • 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
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 infusion week 25 up to week 104

Number of adverse events, by type and severity, from week 25 up to week 104

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious TEAE	2 events	9 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any adverse event	174 events	355 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any non-treatment emergent serious adverse event	0 events	1 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any treatment emergent adverse event (TEAE)	174 events	351 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any drug-related TEAE	69 events	202 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any non-serious TEAE	172 events	342 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious drug-related TEAE	0 events	0 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any TEAE leading to study and/or treatment withdrawal	0 events	0 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any drug-related TEAE leading to study and/or treatment withdrawal	0 events	0 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any serious TEAE leading to study and/or treatment withdrawal	0 events	0 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any TEAE leading to death	0 events	0 events
Safety as Measured by Adverse Events Frequencies (by Type and Severity) Any Infusion Related Reaction	46 events	78 events

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

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

The observed SOBI003 serum concentration immediately before the start of infusion of SOBI003 (CPre-dose) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 38 - central serum	—	120.0 ng/mL Standard Deviation NA Only one sample analyzed
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 78 - central serum	47.0 ng/mL Standard Deviation NA Only one sample analyzed	75.0 ng/mL Standard Deviation NA Only one sample analyzed
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 104 - central serum	2610 ng/mL Standard Deviation NA Only one sample analyzed	—
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 38 - peripheral serum	49 ng/mL Standard Deviation NA Only one sample analyzed	30 ng/mL Standard Deviation 14.142
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 52 - peripheral serum	123 ng/mL Standard Deviation NA Only one sample analyzed	11770 ng/mL Standard Deviation 16312
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 78 - peripheral serum	208.5 ng/mL Standard Deviation 234.05	—
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 Week 104 - peripheral serum	765.5 ng/mL Standard Deviation 125.16	66.33 ng/mL Standard Deviation 49.571

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

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

The observed SOBI003 serum concentration at the end of infusion of SOBI003 (CEnd of inf) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 38 - central serum	—	210000 ng/mL Standard Deviation NA Only one sample analyzed
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 38 - peripheral serum	14370 ng/mL Standard Deviation 14583	109500 ng/mL Standard Deviation 3535.5
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 52 - central serum	7900 ng/mL Standard Deviation NA Only one sample analyzed	203000 ng/mL Standard Deviation NA Only one sample analyzed
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 52 - peripheral serum	72000 ng/mL Standard Deviation 37194	86510 ng/mL Standard Deviation 122320
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 78 - peripheral serum	74450 ng/mL Standard Deviation 105310	229500 ng/mL Standard Deviation 101120
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 104 - central serum	79700 ng/mL Standard Deviation NA Only one sample analyzed	—
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 Week 104 - peripheral serum	292599 ng/mL Standard Deviation 37477	195000 ng/mL Standard Deviation 72125

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

The time of the end of infusion of SOBI003 (tEnd of inf) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Time of the End of the Infusion of SOBI003 Week 38 - central serum	—	6.20 Hours Interval 6.2 to 6.2
The Time of the End of the Infusion of SOBI003 Week 52 - central serum	4.50 Hours Interval 4.5 to 4.5	4.170 Hours Interval 4.17 to 4.17
The Time of the End of the Infusion of SOBI003 Week 104 - central serum	4.47 Hours Interval 4.47 to 4.47	—
The Time of the End of the Infusion of SOBI003 Week 38 - peripheral serum	4.5 Hours Interval 4.08 to 6.25	4.825 Hours Interval 4.33 to 5.32
The Time of the End of the Infusion of SOBI003 Week 52- peripheral serum	4.775 Hours Interval 4.08 to 5.47	5.845 Hours Interval 4.17 to 7.52
The Time of the End of the Infusion of SOBI003 Week 78- peripheral serum	4.50 Hours Interval 4.18 to 5.88	8.575 Hours Interval 4.73 to 12.4
The Time of the End of the Infusion of SOBI003 Week 104- peripheral serum	5.030 Hours Interval 4.03 to 6.03	8.540 Hours Interval 4.25 to 12.8

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

The maximum observed serum concentration of SOBI003 (Cmax) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Maximum Observed Serum Concentration of SOBI003 Week 38 - central serum	—	105000 ng/mL Interval 32.0 to 210000.0
The Maximum Observed Serum Concentration of SOBI003 Week 52 - central serum	—	203000 ng/mL Interval 203000.0 to 203000.0
The Maximum Observed Serum Concentration of SOBI003 Week 78 - central serum	136.0 ng/mL Interval 136.0 to 136.0	75.0 ng/mL Interval 75.0 to 75.0
The Maximum Observed Serum Concentration of SOBI003 Week 104 - central serum	79700 ng/mL Interval 79700.0 to 79700.0	—
The Maximum Observed Serum Concentration of SOBI003 Week 38 - peripheral serum	7690 ng/mL Interval 4330.0 to 31100.0	109500 ng/mL Interval 107000.0 to 112000.0
The Maximum Observed Serum Concentration of SOBI003 Week 52 - peripheral serum	45700 ng/mL Interval 154.0 to 98300.0	23300 ng/mL Interval 11600.0 to 173000.0
The Maximum Observed Serum Concentration of SOBI003 Week 78 - peripheral serum	195000 ng/mL Interval 28000.0 to 243000.0	229500 ng/mL Interval 158000.0 to 301000.0
The Maximum Observed Serum Concentration of SOBI003 Week 104 - peripheral serum	292500 ng/mL Interval 266000.0 to 319000.0	144000 ng/mL Interval 25000.0 to 246000.0

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

The time after start of infusion at which the maximum serum concentration is observed (tmax) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 52 - peripheral serum	5.47 Hours Interval 4.08 to 26.5	7.52 Hours Interval 0.0 to 24.5
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 78 - peripheral serum	5.88 Hours Interval 4.5 to 168.0	8.575 Hours Interval 4.73 to 12.4
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 104 - peripheral serum	5.03 Hours Interval 4.03 to 6.03	12.83 Hours Interval 4.25 to 23.7
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 38 - central serum	—	87.96 Hours Interval 8.17 to 168.0
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 52 - central serum	4.50 Hours Interval 4.5 to 4.5	4.170 Hours Interval 4.17 to 4.17
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 78 - central serum	168 Hours Interval 168.0 to 168.0	0 Hours Interval 0.0 to 0.0
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 104 - central serum	4.47 Hours Interval 4.47 to 4.47	—
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed Week 38 - peripheral serum	4.5 Hours Interval 4.08 to 6.25	4.825 Hours Interval 4.33 to 5.32

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

The minimum observed serum concentration of SOBI003 (CTrough) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
The Minimum Observed Serum Concentration of SOBI003 Week 38 - central serum	—	68.0 ng/mL Interval 32.0 to 104.0
The Minimum Observed Serum Concentration of SOBI003 Week 78 - central serum	47.0 ng/mL Interval 47.0 to 47.0	75.0 ng/mL Interval 75.0 to 75.0
The Minimum Observed Serum Concentration of SOBI003 Week 104 - central serum	2610 ng/mL Interval 2610.0 to 2610.0	—
The Minimum Observed Serum Concentration of SOBI003 Week 38 - peripheral serum	34 ng/mL Interval 34.0 to 34.0	30 ng/mL Interval 20.0 to 40.0
The Minimum Observed Serum Concentration of SOBI003 Week 52 - peripheral serum	138.5 ng/mL Interval 123.0 to 154.0	25 ng/mL Interval 11.0 to 45.0
The Minimum Observed Serum Concentration of SOBI003 Week 78 - peripheral serum	362 ng/mL Interval 43.0 to 28000.0	85 ng/mL Interval 85.0 to 85.0
The Minimum Observed Serum Concentration of SOBI003 Week 104 - peripheral serum	704.5 ng/mL Interval 555.0 to 854.0	75 ng/mL Interval 13.0 to 111.0

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

Clearance (CL) of SOBI003 Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Clearance Week 78 - central serum	208 mL/min Interval 208.0 to 208.0	—
Clearance Week 104 - central serum	1.6 mL/min Interval 1.6 to 1.6	—
Clearance Week 38 - peripheral serum	—	0.661 mL/min Interval 0.661 to 0.661
Clearance Week 52 - peripheral serum	3.51 mL/min Interval 3.51 to 3.51	—
Clearance Week 104 - peripheral serum	2.21 mL/min Interval 2.21 to 2.21	3.61 mL/min Interval 3.61 to 3.61

SECONDARY outcome

Timeframe: 0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

Area under the SOBI003 serum concentration-time curve from time 0 to 168 hours (AUC 0-168h) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours Week 78 - central serum	15400 h*ng/mL Interval 15400.0 to 15400.0	—
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours Week 104 - central serum	2040000 h*ng/mL Interval 2040000.0 to 2040000.0	—
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours Week 38 - peripheral serum	—	2880000 h*ng/mL Interval 2880000.0 to 2880000.0
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours Week 52 - peripheral serum	1110000 h*ng/mL Interval 1110000.0 to 1110000.0	—
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours Week 104 - peripheral serum	4390000 h*ng/mL Interval 4390000.0 to 4390000.0	2770000 h*ng/mL Interval 2770000.0 to 2770000.0

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

The half-life of SOBI003 in serum (T1/2) Blood samples for serum PK analysis were collected either by centrally (i.e., using a catheter in the central venous port) or peripheral (i.e., by venipuncture). Central venous sampling is more convenient than repeated venipuncture.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 52 and 104

Population: Number analysed are available samples

Concentration of SOBI003 in cerebrospinal fluid

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
SOBI003 Concentration in Cerebrospinal Fluid Week 52	15.7 ng/mL Interval 15.7 to 15.7	92.3 ng/mL Interval 73.6 to 115.0
SOBI003 Concentration in Cerebrospinal Fluid Week 104	118.35 ng/mL Interval 95.7 to 141.0	57.1 ng/mL Interval 41.5 to 147.0

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Number of Patients Having Anti-drug Antibodies in Serum Week 38	3 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Serum Week 52	3 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Serum Week 78	3 Participants	2 Participants
Number of Patients Having Anti-drug Antibodies in Serum Week 104	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Weeks 52 and 104

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

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid Week 52	2 Participants	3 Participants
Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid Week 104	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Weeks 52 and 104

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

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid Week 52	-1.19 mg/L Interval -4.91 to 0.1	-3.47 mg/L Interval -23.2 to -2.579
Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid Week 104	-6.07 mg/L Interval -6.67 to -4.42	-3.59 mg/L Interval -24.7 to -2.18

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Change from baseline in Heparan sulfate, in mg/L, levels in serum

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Heparan Sulfate Levels in Serum Week 38	-1.811 mg/L Interval -2.168 to -1.793	-1.88 mg/L Interval -3.721 to -1.854
Change From Baseline in Heparan Sulfate Levels in Serum Week 52	-1.76 mg/L Interval -2.169 to -1.644	-2.25 mg/L Interval -3.735 to -1.18
Change From Baseline in Heparan Sulfate Levels in Serum Week 78	-1.729 mg/L Interval -2.41 to -1.686	-2.01 mg/L Interval -3.05 to -0.97
Change From Baseline in Heparan Sulfate Levels in Serum Week 104	-2.21 mg/L Interval -2.41 to 0.21	-2.24 mg/L Interval -3.708 to -1.91

SECONDARY outcome

Timeframe: Weeks 38, 52, 78 and 104

Population: Number of analysed are available samples

Change from baseline in Heparan sulfate levels, in g/mol, in urine

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Heparan Sulfate Levels in Urine Week 38	-447.2 g/mol Interval -552.82 to -340.1	-692.78 g/mol Interval -697.12 to -382.65
Change From Baseline in Heparan Sulfate Levels in Urine Week 52	-464.4 g/mol Interval -559.02 to -411.67	-698.79 g/mol Interval -701.99 to -388.86
Change From Baseline in Heparan Sulfate Levels in Urine Week 78	-512.19 g/mol Interval -599.7 to -424.68	-494.610 g/mol Interval -747.22 to -242.0
Change From Baseline in Heparan Sulfate Levels in Urine Week 104	-578.89 g/mol Interval -709.47 to -489.68	-726.24 g/mol Interval -753.97 to -381.45

SECONDARY outcome

Timeframe: Weeks 52 and 104

Population: Number of analysed are number of assessments

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. These results are truly "unitless"/"dimensionless" because they represents quotients of values from the same scale, which means that the units in the denominator and

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Neurocognitive Development Quotient Week 52	-8.97 Unitless Interval -18.0 to -6.9	-31.74 Unitless Interval -48.9 to -14.6
Change From Baseline in Neurocognitive Development Quotient Week 104	-16.28 Unitless Interval -32.9 to -11.7	-24.94 Unitless Interval -44.6 to -11.3

SECONDARY outcome

Timeframe: Week 52 and 104

Population: Number of analyses are available assessments

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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Age-equivalence Score Week 52	-1.0 Months Interval -2.0 to 2.0	-1.0 Months Interval -2.0 to 0.0
Change From Baseline in Age-equivalence Score Week 104	-3.0 Months Interval -4.0 to 1.0	5.0 Months Interval -1.0 to 10.0

SECONDARY outcome

Timeframe: Week 52 and 104

Population: Number of analyses are available assessments

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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. Week 52	14.0 Months Interval 10.0 to 31.0	16.0 Months Interval 12.0 to 20.0
Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. Week 104	13.0 Months Interval 8.0 to 29.0	19.0 Months Interval 19.0 to 36.0

SECONDARY outcome

Timeframe: Week 52 and 104

Population: Number of analysed are available assessments

The age equivalent score represents 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 either by the Bayley Scales of Infant and Toddler Development®, third edition, (BSID-III) cognitive subtest or the Kaufman Assessment Battery for Children, Second edition (KABC-II) depending on chronological age of the subject. Quotient between age equivalent score and age, 0 - 100%, where high values are desirable. The BSID-III is an individually administered test designed to assess developmental functioning of infants and toddlers. The BSID-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The KABC-II is a clinical instrument for assessing cognitive development. The unit and measurement is the same in both scales (BSID-III and KABC-II): Age-equivalent score.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. Week 52	-1.0 Months Interval -2.0 to 2.0	-1.0 Months Interval -2.0 to 0.0
Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. Week 104	-3.0 Months Interval -4.0 to 1.0	5.0 Months Interval -1.0 to 10.0

SECONDARY outcome

Timeframe: Week 52 and 104

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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Age-equivalence Score as Assessed by VABS-II Week 52	15 Months Interval 15.0 to 26.0	28 Months Interval 13.0 to 37.0
Age-equivalence Score as Assessed by VABS-II Week 104	16 Months Interval 13.0 to 21.0	23 Months Interval 20.0 to 43.0

SECONDARY outcome

Timeframe: Week 52 and 104

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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Age-equivalence Score as Assessed by VABS-II Week 52	-1 Months Interval -12.0 to 2.0	1 Months Interval 0.0 to 4.0
Change From Baseline in Age-equivalence Score as Assessed by VABS-II Week 104	-6 Months Interval -11.0 to 0.0	8 Months Interval -5.0 to 10.0

SECONDARY outcome

Timeframe: Week 52 and 104

Population: Number analysed is available assessments

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) at weeks 52 and 104.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Gray Matter Volume Week 52	-24.629 mL Interval -34.32 to 66.87	19.485 mL Interval -62.32 to 101.29
Change From Baseline in Gray Matter Volume Week 104	-53.584 mL Interval -161.03 to 53.86	13.387 mL Interval -45.41 to 72.18

SECONDARY outcome

Timeframe: Week 52 and 104

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. Lower scores indicate better functioning. Min score = 0, and max score = 144.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Pediatric Quality of Life Inventory (PedsQL™) Total Score Week 52	53.4 Units on a scale Standard Deviation 3.9	72.2 Units on a scale Standard Deviation 11.6
Pediatric Quality of Life Inventory (PedsQL™) Total Score Week 104	55.9 Units on a scale Standard Deviation 10.2	76.5 Units on a scale Standard Deviation 3.8

SECONDARY outcome

Timeframe: Week 52 and 104

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. Higher scores indicate better functioning. Min score = 0, and max score = 144.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score Week 52	-17.0 Units on a scale Standard Deviation 25.9	-3.7 Units on a scale Standard Deviation 24.2
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score Week 104	-14.5 Units on a scale Standard Deviation 14.9	0.6 Units on a scale Standard Deviation 21.0

SECONDARY outcome

Timeframe: Week 52 and 104

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 Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning. Min score = 0, and max score = 144.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=3 Participants SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
PedsQL™ Family Impact Module Total Score Week 52	66.7 Units on a scale Standard Deviation 30.6	70.0 Units on a scale Standard Deviation 26.5
PedsQL™ Family Impact Module Total Score Week 104	73.3 Units on a scale Standard Deviation 34.0	70.0 Units on a scale Standard Deviation 26.5

SECONDARY outcome

Timeframe: Week 52 and 104

Population: Number analysed is available assessments

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 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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 Participants SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Change From Baseline in PedsQL™ Family Impact Module Total Score Week 52	16.7 Units on a scale Standard Deviation 12.6	0.0 Units on a scale Standard Deviation 0.0
Change From Baseline in PedsQL™ Family Impact Module Total Score Week 104	23.3 Units on a scale Standard Deviation 31.8	0.0 Units on a scale Standard Deviation 0.0

Adverse Events

Dose Group 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Group 2

Serious events: 2 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 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Dose Group 2 n=3 participants at risk SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • Number of events 1 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.	33.3% 1/3 • Number of events 2 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Device related infection	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Infection	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Influenza	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Infections and infestations Staphylococcal infection	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.
Injury, poisoning and procedural complications Incision site haemorrhage	0.00% 0/3 • The period for recording adverse events, including Serious Adverse Events (SAEs), began Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of 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 Day 1 of week 25, when first dose in study SOBI003-002 was given, and ended at completion of week 104 visit. In addition SAEs was reported from the time of signing the informed consent form until 28 days past the last dose of SOBI003.

Other adverse events

Additional Information

Global Communication

Sobi

Phone: +4686972000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place