A Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients

• Sponsor: Swedish Orphan Biovitrum (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03811028
• Collaborator: (none)
• Enrollment: 6
• Locations: 3
• Arm: 1
• Actual Duration (Months): 27.6
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aim of the present study is to assess the safety, tolerability and efficacy of long-term SOBI003 treatment. SOBI003 is a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

Condition or Disease	Intervention/Treatment	Phase
Sanfilippo Syndrome Type A (MPS IIIA)	Drug: SOBI003	Phase 1/Phase 2

Detailed Description

This is an open, single-arm, multicenter extension study to assess the safety, tolerability and efficacy of long-term SOBI003 treatment in pediatric MPS IIIA patients. The study is an extension of the First in Human (FIH) SOBI003-001 study, allowing continuous treatment of SOBI003 for up to 2 years. Study patients who complete Week 24 of the FIH study (SOBI003-001) will be invited to continue to Week 25 in the extension study.

When entering the extension study, these patients will receive the highest dose that has been declared safe in the ongoing FIH study (SOBI003-001). Upon completion of the FIH study, an analysis aimed at selecting the dose for forthcoming studies will take place. Once the dose has been selected, this dose will be applied to all patients enrolled in the extension study. The total duration of the extension study for an individual patient is 80 weeks, resulting in a total of 104 weeks (2 years) of SOBI003 treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open, Single-arm, Multicenter Extension Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients
• Actual Study Start Date: Jan 19, 2019
• Actual Primary Completion Date: Apr 30, 2021
• Actual Study Completion Date: May 7, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: SOBI003 SOBI003 solution, 20 mg/mL, is mixed with NaCl 0.9% infusion solution prior to administration. For a bodyweight < 25 kg, the total infusion volume is 100 mL. For a bodyweight ≥ 25 kg, the total infusion volume is 250 mL. SOBI003 is administered as i.v. infusions given once weekly for a duration of 80 weeks (from Week 25 until Week 104 following the first 24 weeks of SOBI003 administration in the FIH study (SOBI003-001) study. The SOBI003 dose will be adjusted to the highest dose that has been declared safe by the safety review committee on the FIH study.Hence, dose adjustments may occur a couple of times on the extension study until the final decided dose has been determined.

Drug: SOBI003; weekly i.v. infusion; Other Names: Modified recombinant human sulphamidase

Outcome Measures

Primary Outcome Measures

1. Safety as Measured by Adverse Events Frequencies (by Type and Severity) [From infusion week 25 up to week 104]

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

Secondary Outcome Measures

1. The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 [Weeks 38, 52, 78 and 104]

   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.

2. The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 [Weeks 38, 52, 78 and 104]

   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.

3. The Time of the End of the Infusion of SOBI003 [Weeks 38, 52, 78 and 104]

   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.

4. The Maximum Observed Serum Concentration of SOBI003 [Weeks 38, 52, 78 and 104]

   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.

5. The Time at Which the Maximum Serum Concentration of SOBI003 is Observed [Weeks 38, 52, 78 and 104]

   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.

6. The Minimum Observed Serum Concentration of SOBI003 [Weeks 38, 52, 78 and 104]

   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.

7. Clearance [Weeks 38, 52, 78 and 104]

   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.

8. Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours [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]

   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.

9. The Half-life [Weeks 38, 52, 78 and 104]

   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.

10. SOBI003 Concentration in Cerebrospinal Fluid [Weeks 52 and 104]

    Concentration of SOBI003 in cerebrospinal fluid

11. Number of Patients Having Anti-drug Antibodies in Serum [Weeks 38, 52, 78 and 104]

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

12. Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid [Weeks 52 and 104]

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

13. Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid [Weeks 52 and 104]

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

14. Change From Baseline in Heparan Sulfate Levels in Serum [Weeks 38, 52, 78 and 104]

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

15. Change From Baseline in Heparan Sulfate Levels in Urine [Weeks 38, 52, 78 and 104]

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

16. Change From Baseline in Neurocognitive Development Quotient [Weeks 52 and 104]

    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

17. Change From Baseline in Age-equivalence Score [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 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.

18. Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. [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.

19. Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. [Week 52 and 104]

    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.

20. Age-equivalence Score as Assessed by VABS-II [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.

21. Change From Baseline in Age-equivalence Score as Assessed by VABS-II [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.

22. Change From Baseline in Gray Matter Volume [Week 52 and 104]

    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.

23. Pediatric Quality of Life Inventory (PedsQL™) Total Score [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.

24. Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score [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.

25. PedsQL™ Family Impact Module Total Score [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.

26. Change From Baseline in PedsQL™ Family Impact Module Total Score [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 78 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of study SOBI003-001

• Informed consent obtained from the patient´s legally authorized representative

Exclusion Criteria:

• If, in the opinion of the investigator, there are patient specific safety concerns that contraindicates further treatment with SOBI003

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children´s Hospital and research center	Oakland	California	United States	94609
2	University of North Carolina hospitals	Chapel Hill	North Carolina	United States	27599
3	Gazi University Hospital	Ankara		Turkey

Sponsors and Collaborators

• Swedish Orphan Biovitrum

Investigators

• Principal Investigator: Paul Harmatz, MD, Children´s Hospital and Research Center, Oakland

Study Documents (Full-Text)

• Study Protocol - Jun 29, 2018
• Statistical Analysis Plan - Sep 13, 2018

More Information

Publications

None provided.

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT03811028
• Other Study ID Numbers: SOBI003-002
• First Posted: Jan 22, 2019
• Last Update Posted: Feb 25, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Mucopolysaccharidosis III

Study Results

Participant Flow

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dose Group 1	Dose Group 2	Total
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	Total of all reporting groups
Overall Participants	3	3	6
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	52.0 (23.8)	34.7 (12.7)	43.3 (19.5)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 33.3%	2 33.3%
Male	2 66.7%	2 66.7%	4 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 100%	3 100%	6 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Safety as Measured by Adverse Events Frequencies (by Type and Severity)
Description	Number of adverse events, by type and severity, from week 25 up to week 104
Time Frame	From infusion week 25 up to week 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Any adverse event	174	355
Any non-treatment emergent serious adverse event	0	1
Any treatment emergent adverse event (TEAE)	174	351
Any drug-related TEAE	69	202
Any non-serious TEAE	172	342
Any serious TEAE	2	9
Any serious drug-related TEAE	0	0
Any TEAE leading to study and/or treatment withdrawal	0	0
Any drug-related TEAE leading to study and/or treatment withdrawal	0	0
Any serious TEAE leading to study and/or treatment withdrawal	0	0
Any TEAE leading to death	0	0
Any Infusion Related Reaction	46	78

2. Secondary Outcome

Title	The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

The table report number of available pharmacokinetic (PK) samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	120.0 (NA)
Week 78 - central serum	47.0 (NA)	75.0 (NA)
Week 104 - central serum	2610 (NA)
Week 38 - peripheral serum	49 (NA)	30 (14.142)
Week 52 - peripheral serum	123 (NA)	11770 (16312)
Week 78 - peripheral serum	208.5 (234.05)
Week 104 - peripheral serum	765.5 (125.16)	66.33 (49.571)

3. Secondary Outcome

Title	The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

The table report number of available pharmacokinetic (PK) samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	210000 (NA)
Week 38 - peripheral serum	14370 (14583)	109500 (3535.5)
Week 52 - central serum	7900 (NA)	203000 (NA)
Week 52 - peripheral serum	72000 (37194)	86510 (122320)
Week 78 - peripheral serum	74450 (105310)	229500 (101120)
Week 104 - central serum	79700 (NA)
Week 104 - peripheral serum	292599 (37477)	195000 (72125)

4. Secondary Outcome

Title	The Time of the End of the Infusion of SOBI003
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	6.20
Week 52 - central serum	4.50	4.170
Week 104 - central serum	4.47
Week 38 - peripheral serum	4.5	4.825
Week 52- peripheral serum	4.775	5.845
Week 78- peripheral serum	4.50	8.575
Week 104- peripheral serum	5.030	8.540

5. Secondary Outcome

Title	The Maximum Observed Serum Concentration of SOBI003
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	105000
Week 52 - central serum	203000
Week 78 - central serum	136.0	75.0
Week 104 - central serum	79700
Week 38 - peripheral serum	7690	109500
Week 52 - peripheral serum	45700	23300
Week 78 - peripheral serum	195000	229500
Week 104 - peripheral serum	292500	144000

6. Secondary Outcome

Title	The Time at Which the Maximum Serum Concentration of SOBI003 is Observed
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	87.96
Week 52 - central serum	4.50	4.170
Week 78 - central serum	168	0
Week 104 - central serum	4.47
Week 38 - peripheral serum	4.5	4.825
Week 52 - peripheral serum	5.47	7.52
Week 78 - peripheral serum	5.88	8.575
Week 104 - peripheral serum	5.03	12.83

7. Secondary Outcome

Title	The Minimum Observed Serum Concentration of SOBI003
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38 - central serum	68.0
Week 78 - central serum	47.0	75.0
Week 104 - central serum	2610
Week 38 - peripheral serum	34	30
Week 52 - peripheral serum	138.5	25
Week 78 - peripheral serum	362	85
Week 104 - peripheral serum	704.5	75

8. Secondary Outcome

Title	Clearance
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 78 - central serum	208
Week 104 - central serum	1.6
Week 38 - peripheral serum	0.661
Week 52 - peripheral serum	3.51
Week 104 - peripheral serum	2.21	3.61

9. Secondary Outcome

Title	Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 78 - central serum	15400
Week 104 - central serum	2040000
Week 38 - peripheral serum	2880000
Week 52 - peripheral serum	1110000
Week 104 - peripheral serum	4390000	2770000

10. Secondary Outcome

Title	The Half-life
Description	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.
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	0	0

11. Secondary Outcome

Title	SOBI003 Concentration in Cerebrospinal Fluid
Description	Concentration of SOBI003 in cerebrospinal fluid
Time Frame	Weeks 52 and 104

Outcome Measure Data

Analysis Population Description

Number analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	15.7	92.3
Week 104	118.35	57.1

12. Secondary Outcome

Title	Number of Patients Having Anti-drug Antibodies in Serum
Description	Number of patients in each dose group having anti-drug antibodies in serum
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38	3 100%	3 100%
Week 52	3 100%	3 100%
Week 78	3 100%	2 66.7%
Week 104	3 100%	3 100%

13. Secondary Outcome

Title	Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid
Description	Number of patients in each dose group having anti-drug antibodies cerebrospinal fluid
Time Frame	Weeks 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	2 66.7%	3 100%
Week 104	3 100%	3 100%

14. Secondary Outcome

Title	Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid
Description	Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid
Time Frame	Weeks 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-1.19	-3.47
Week 104	-6.07	-3.59

15. Secondary Outcome

Title	Change From Baseline in Heparan Sulfate Levels in Serum
Description	Change from baseline in Heparan sulfate, in mg/L, levels in serum
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38	-1.811	-1.88
Week 52	-1.76	-2.25
Week 78	-1.729	-2.01
Week 104	-2.21	-2.24

16. Secondary Outcome

Title	Change From Baseline in Heparan Sulfate Levels in Urine
Description	Change from baseline in Heparan sulfate levels, in g/mol, in urine
Time Frame	Weeks 38, 52, 78 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available samples

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 38	-447.2	-692.78
Week 52	-464.4	-698.79
Week 78	-512.19	-494.610
Week 104	-578.89	-726.24

17. Secondary Outcome

Title	Change From Baseline in Neurocognitive Development Quotient
Description	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
Time Frame	Weeks 52 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are number of assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-8.97	-31.74
Week 104	-16.28	-24.94

18. Secondary Outcome

Title	Change From Baseline in Age-equivalence Score
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

Number of analyses are available assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-1.0	-1.0
Week 104	-3.0	5.0

19. Secondary Outcome

Title	Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

Number of analyses are available assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	14.0	16.0
Week 104	13.0	19.0

20. Secondary Outcome

Title	Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

Number of analysed are available assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-1.0	-1.0
Week 104	-3.0	5.0

21. Secondary Outcome

Title	Age-equivalence Score as Assessed by VABS-II
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	15	28
Week 104	16	23

22. Secondary Outcome

Title	Change From Baseline in Age-equivalence Score as Assessed by VABS-II
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-1	1
Week 104	-6	8

23. Secondary Outcome

Title	Change From Baseline in Gray Matter Volume
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

Number analysed is available assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-24.629	19.485
Week 104	-53.584	13.387

24. Secondary Outcome

Title	Pediatric Quality of Life Inventory (PedsQL™) Total Score
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	53.4 (3.9)	72.2 (11.6)
Week 104	55.9 (10.2)	76.5 (3.8)

25. Secondary Outcome

Title	Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	-17.0 (25.9)	-3.7 (24.2)
Week 104	-14.5 (14.9)	0.6 (21.0)

26. Secondary Outcome

Title	PedsQL™ Family Impact Module Total Score
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	66.7 (30.6)	70.0 (26.5)
Week 104	73.3 (34.0)	70.0 (26.5)

27. Secondary Outcome

Title	Change From Baseline in PedsQL™ Family Impact Module Total Score
Description	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.
Time Frame	Week 52 and 104

Outcome Measure Data

Analysis Population Description

Number analysed is available assessments

Arm/Group Title	Dose Group 1	Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion	SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
Measure Participants	3	3
Week 52	16.7 (12.6)	0.0 (0.0)
Week 104	23.3 (31.8)	0.0 (0.0)

Adverse Events

Time Frame	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.
Arm/Group Title	Dose Group 1		Dose Group 2
Arm/Group Description	SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion		SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104 SOBI003: weekly i.v. infusion
All Cause Mortality
	Dose Group 1		Dose Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	Dose Group 1		Dose Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/3 (66.7%)
General disorders
Pyrexia	1/3 (33.3%)	1	0/3 (0%)	0
Infections and infestations
Upper respiratory tract infection	1/3 (33.3%)	1	1/3 (33.3%)	2
Device related infection	0/3 (0%)		1/3 (33.3%)	1
Endocarditis	0/3 (0%)		1/3 (33.3%)	1
Infection	0/3 (0%)		1/3 (33.3%)	1
Influenza	0/3 (0%)		1/3 (33.3%)	1
Pneumonia	0/3 (0%)		1/3 (33.3%)	1
Staphylococcal infection	0/3 (0%)		1/3 (33.3%)	1
Injury, poisoning and procedural complications
Incision site haemorrhage	0/3 (0%)		1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Dose Group 1		Dose Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/3 (33.3%)	2	1/3 (33.3%)	2
Cardiac disorders
Aortic valve thickening	0/3 (0%)	0	1/3 (33.3%)	1
Cyanosis	0/3 (0%)	0	1/3 (33.3%)	1
Tachycardia	1/3 (33.3%)	20	3/3 (100%)	28
Ear and labyrinth disorders
Auricular swelling	0/3 (0%)	0	1/3 (33.3%)	1
Otorrhoea	1/3 (33.3%)	1	0/3 (0%)	0
Eye disorders
Eye swelling	0/3 (0%)	0	1/3 (33.3%)	1
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)	1	0/3 (0%)	0
Abdominal pain upper	0/3 (0%)	0	2/3 (66.7%)	2
Abnormal faeces	0/3 (0%)	0	1/3 (33.3%)	1
Aphthous ulcer	1/3 (33.3%)	1	0/3 (0%)	0
Constipation	1/3 (33.3%)	4	0/3 (0%)	0
Dental caries	1/3 (33.3%)	1	0/3 (0%)	0
Diarrhoea	1/3 (33.3%)	1	2/3 (66.7%)	10
Faeces discoloured	0/3 (0%)	0	1/3 (33.3%)	1
Haematochezia	1/3 (33.3%)	1	0/3 (0%)	0
Lip disorder	0/3 (0%)	0	1/3 (33.3%)	1
Nausea	0/3 (0%)	0	2/3 (66.7%)	4
Oral contusion	0/3 (0%)	0	1/3 (33.3%)	1
Retching	0/3 (0%)	0	1/3 (33.3%)	1
Vomiting	3/3 (100%)	17	3/3 (100%)	22
General disorders
Application site erythema	0/3 (0%)	0	1/3 (33.3%)	1
Catheter site extravasation	0/3 (0%)	0	1/3 (33.3%)	1
Catheter site inflammation	1/3 (33.3%)	1	1/3 (33.3%)	1
Catheter site injury	1/3 (33.3%)	1	0/3 (0%)	0
Complication associated with device	0/3 (0%)	0	1/3 (33.3%)	6
Fatigue	0/3 (0%)	0	1/3 (33.3%)	1
Infusion site bruising	1/3 (33.3%)	1	0/3 (0%)	0
Infusion site irritation	0/3 (0%)	0	1/3 (33.3%)	1
Medical device site haemorrhage	1/3 (33.3%)	1	0/3 (0%)	0
Oedema	2/3 (66.7%)	2	0/3 (0%)	0
Pain	1/3 (33.3%)	1	0/3 (0%)	0
Pyrexia	3/3 (100%)	8	3/3 (100%)	11
Immune system disorders
Drug hypersensitivity	1/3 (33.3%)	1	0/3 (0%)	0
Hypersensitivity	1/3 (33.3%)	2	1/3 (33.3%)	1
Seasonal allergy	1/3 (33.3%)	1	0/3 (0%)	0
Infections and infestations
Abscess	1/3 (33.3%)	1	0/3 (0%)	0
Cellulitis	1/3 (33.3%)	1	0/3 (0%)	0
Conjunctivitis	1/3 (33.3%)	1	0/3 (0%)	0
Corona virus infection	0/3 (0%)	0	1/3 (33.3%)	1
Device related infection	0/3 (0%)	0	1/3 (33.3%)	1
Ear infection	1/3 (33.3%)	2	1/3 (33.3%)	1
Endocarditis	0/3 (0%)	0	1/3 (33.3%)	1
Furuncle	1/3 (33.3%)	1	0/3 (0%)	0
Gastroenteritis	2/3 (66.7%)	4	0/3 (0%)	0
Infection	0/3 (0%)	0	1/3 (33.3%)	1
Influenza	1/3 (33.3%)	1	1/3 (33.3%)	1
Nasopharyngitis	0/3 (0%)	0	1/3 (33.3%)	1
Otitis media acute	0/3 (0%)	0	1/3 (33.3%)	1
Pharyngitis streptococcal	1/3 (33.3%)	1	0/3 (0%)	0
Pneumonia	0/3 (0%)	0	1/3 (33.3%)	1
Staphylococcal infection	0/3 (0%)	0	1/3 (33.3%)	1
Streptococcal infection	1/3 (33.3%)	1	0/3 (0%)	0
Tonsillitis	0/3 (0%)	0	1/3 (33.3%)	1
Upper respiratory tract infection	3/3 (100%)	17	2/3 (66.7%)	12
Viral infection	1/3 (33.3%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	1/3 (33.3%)	1	1/3 (33.3%)	2
Contusion	1/3 (33.3%)	2	3/3 (100%)	8
Fall	1/3 (33.3%)	2	1/3 (33.3%)	8
Foreign body in gastrointestinal tract	0/3 (0%)	0	1/3 (33.3%)	1
Human bite	1/3 (33.3%)	3	0/3 (0%)	0
Incision site haemorrhage	0/3 (0%)	0	1/3 (33.3%)	1
Lip injury	0/3 (0%)	0	1/3 (33.3%)	1
Scratch	1/3 (33.3%)	1	1/3 (33.3%)	6
Skin abrasion	0/3 (0%)	0	1/3 (33.3%)	10
Soft tissue injury	1/3 (33.3%)	1	0/3 (0%)	0
Vascular access complication	0/3 (0%)	0	2/3 (66.7%)	4
Vascular access site occlusion	1/3 (33.3%)	4	2/3 (66.7%)	5
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)	0	1/3 (33.3%)	3
Blood fibrinogen increased	0/3 (0%)	0	1/3 (33.3%)	2
Blood pressure diastolic increased	0/3 (0%)	0	1/3 (33.3%)	1
Blood pressure systolic increased	0/3 (0%)	0	1/3 (33.3%)	1
C-reactive protein increased	0/3 (0%)	0	1/3 (33.3%)	2
CSF glucose decreased	0/3 (0%)	0	1/3 (33.3%)	1
CSF protein increased	0/3 (0%)	0	1/3 (33.3%)	1
Cardiac murmur	0/3 (0%)	0	1/3 (33.3%)	1
Eosinophil count increased	0/3 (0%)	0	1/3 (33.3%)	2
Haemoglobin increased	0/3 (0%)	0	1/3 (33.3%)	1
Heart rate increased	0/3 (0%)	0	1/3 (33.3%)	1
Monocyte count decreased	0/3 (0%)	0	1/3 (33.3%)	1
Neutrophil count increased	0/3 (0%)	0	1/3 (33.3%)	1
Oxygen saturation decreased	0/3 (0%)	0	2/3 (66.7%)	26
Platelet count decreased	0/3 (0%)	0	1/3 (33.3%)	1
Red blood cell count increased	0/3 (0%)	0	1/3 (33.3%)	1
Vitamin D decreased	1/3 (33.3%)	1	0/3 (0%)	0
Weight decreased	1/3 (33.3%)	1	0/3 (0%)	0
White blood cell count increased	0/3 (0%)	0	1/3 (33.3%)	2
Musculoskeletal and connective tissue disorders
Muscle tightness	0/3 (0%)	0	1/3 (33.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/3 (0%)	0	1/3 (33.3%)	1
Nervous system disorders
Ataxia	1/3 (33.3%)	1	0/3 (0%)	0
Clonus	0/3 (0%)	0	1/3 (33.3%)	2
Drooling	0/3 (0%)	0	1/3 (33.3%)	2
Tremor	1/3 (33.3%)	1	2/3 (66.7%)	6
Product Issues
Device damage	1/3 (33.3%)	2	0/3 (0%)	0
Device dislocation	1/3 (33.3%)	2	2/3 (66.7%)	2
Device malfunction	1/3 (33.3%)	1	0/3 (0%)	0
Psychiatric disorders
Abnormal behaviour	1/3 (33.3%)	1	0/3 (0%)	0
Anxiety	1/3 (33.3%)	1	0/3 (0%)	0
Irritability	1/3 (33.3%)	1	0/3 (0%)	0
Restlessness	0/3 (0%)	0	2/3 (66.7%)	8
Sleep disorder	0/3 (0%)	0	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1	2/3 (66.7%)	10
Hypoxia	0/3 (0%)	0	1/3 (33.3%)	2
Nasal congestion	0/3 (0%)	0	1/3 (33.3%)	3
Rhinorrhoea	2/3 (66.7%)	2	1/3 (33.3%)	1
Sneezing	1/3 (33.3%)	1	0/3 (0%)	0
Tachypnoea	0/3 (0%)	0	1/3 (33.3%)	5
Wheezing	0/3 (0%)	0	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/3 (33.3%)	1	0/3 (0%)	0
Dermatitis allergic	1/3 (33.3%)	1	0/3 (0%)	0
Dermatitis contact	1/3 (33.3%)	2	0/3 (0%)	0
Dermatitis diaper	1/3 (33.3%)	1	2/3 (66.7%)	5
Dry skin	0/3 (0%)	0	1/3 (33.3%)	2
Erythema	1/3 (33.3%)	1	2/3 (66.7%)	22
Generalised erythema	0/3 (0%)	0	1/3 (33.3%)	7
Hyperhidrosis	0/3 (0%)	0	1/3 (33.3%)	1
Hyperkeratosis	0/3 (0%)	0	1/3 (33.3%)	1
Livedo reticularis	0/3 (0%)	0	1/3 (33.3%)	1
Rash	1/3 (33.3%)	13	2/3 (66.7%)	4
Rash erythematous	0/3 (0%)	0	1/3 (33.3%)	13
Rash maculo-papular	1/3 (33.3%)	2	0/3 (0%)	0
Skin discolouration	0/3 (0%)	0	1/3 (33.3%)	2
Skin fissures	1/3 (33.3%)	1	1/3 (33.3%)	1
Skin irritation	1/3 (33.3%)	1	0/3 (0%)	0
Swelling face	0/3 (0%)	0	1/3 (33.3%)	1
Urticaria	2/3 (66.7%)	20	3/3 (100%)	20
Vascular disorders
Flushing	0/3 (0%)	0	3/3 (100%)	5
Hyperaemia	1/3 (33.3%)	1	0/3 (0%)	0
Hypertension	0/3 (0%)	0	1/3 (33.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.