Sanfilippo Syndrome Type A (MPS IIIA)
Conditions
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).
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.
Interventions
DRUGSOBI003
weekly i.v. infusion
Sponsors
Swedish Orphan Biovitrum
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 78 Months
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| SOBI003 Concentration in Cerebrospinal Fluid | Weeks 52 and 104 | Concentration of SOBI003 in cerebrospinal fluid |
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Group 1 SOBI003 initial dose 3 mg/kg, once weekly from infusion week 25 to week 104
SOBI003: weekly i.v. infusion | 3 |
| Dose Group 2 SOBI003 initial dose 10 mg/kg, once weekly from infusion week 25 to week 104
SOBI003: weekly i.v. infusion | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Dose Group 2 | Total | Dose Group 1 |
|---|---|---|---|
| Age, Continuous | 34.7 months STANDARD_DEVIATION 12.7 | 43.3 months STANDARD_DEVIATION 19.5 | 52.0 months STANDARD_DEVIATION 23.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 |
Outcome results
Primary
Safety as Measured by Adverse Events Frequencies (by Type and Severity)
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any adverse event | 174 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-treatment emergent serious adverse event | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any treatment emergent adverse event (TEAE) | 174 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE | 69 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-serious TEAE | 172 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE | 2 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious drug-related TEAE | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to death | 0 events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any Infusion Related Reaction | 46 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to death | 0 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any adverse event | 355 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious drug-related TEAE | 0 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-treatment emergent serious adverse event | 1 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any treatment emergent adverse event (TEAE) | 351 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE | 202 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any Infusion Related Reaction | 78 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-serious TEAE | 342 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE leading to study and/or treatment withdrawal | 0 events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE | 9 events |
Secondary
Age-equivalence Score as Assessed by VABS-II
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Age-equivalence Score as Assessed by VABS-II | Week 52 | 15 Months |
| Dose Group 1 | Age-equivalence Score as Assessed by VABS-II | Week 104 | 16 Months |
| Dose Group 2 | Age-equivalence Score as Assessed by VABS-II | Week 52 | 28 Months |
| Dose Group 2 | Age-equivalence Score as Assessed by VABS-II | Week 104 | 23 Months |
Secondary
Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
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
Population: Number of analyses are available assessments
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. | Week 104 | 13.0 Months |
| Dose Group 1 | Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. | Week 52 | 14.0 Months |
| Dose Group 2 | Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. | Week 52 | 16.0 Months |
| Dose Group 2 | Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. | Week 104 | 19.0 Months |
Secondary
Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 78 - central serum | 15400 h*ng/mL |
| Dose Group 1 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 104 - central serum | 2040000 h*ng/mL |
| Dose Group 1 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 52 - peripheral serum | 1110000 h*ng/mL |
| Dose Group 1 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 104 - peripheral serum | 4390000 h*ng/mL |
| Dose Group 2 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 104 - peripheral serum | 2770000 h*ng/mL |
| Dose Group 2 | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 38 - peripheral serum | 2880000 h*ng/mL |
| Unknown | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 78 - peripheral serum | — h*ng/mL |
| Unknown | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 38 - central serum | — h*ng/mL |
| Unknown | Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours | Week 52 - central serum | — h*ng/mL |
Secondary
Change From Baseline in Age-equivalence Score
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
Population: Number of analyses are available assessments
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Age-equivalence Score | Week 52 | -1.0 Months |
| Dose Group 1 | Change From Baseline in Age-equivalence Score | Week 104 | -3.0 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score | Week 52 | -1.0 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score | Week 104 | 5.0 Months |
Secondary
Change From Baseline in Age-equivalence Score as Assessed by VABS-II
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | Week 52 | -1 Months |
| Dose Group 1 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | Week 104 | -6 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | Week 52 | 1 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | Week 104 | 8 Months |
Secondary
Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
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
Population: Number of analysed are available assessments
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | 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 |
| Dose Group 1 | 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 |
| Dose Group 2 | 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 |
| Dose Group 2 | Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II. | Week 104 | 5.0 Months |
Secondary
Change From Baseline in Gray Matter Volume
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
Population: Number analysed is available assessments
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Gray Matter Volume | Week 52 | -24.629 mL |
| Dose Group 1 | Change From Baseline in Gray Matter Volume | Week 104 | -53.584 mL |
| Dose Group 2 | Change From Baseline in Gray Matter Volume | Week 52 | 19.485 mL |
| Dose Group 2 | Change From Baseline in Gray Matter Volume | Week 104 | 13.387 mL |
Secondary
Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid
Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid
Time frame: Weeks 52 and 104
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid | Week 52 | -1.19 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid | Week 104 | -6.07 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid | Week 52 | -3.47 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid | Week 104 | -3.59 mg/L |
Secondary
Change From Baseline in Heparan Sulfate Levels in Serum
Change from baseline in Heparan sulfate, in mg/L, levels in serum
Time frame: Weeks 38, 52, 78 and 104
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 38 | -1.811 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 52 | -1.76 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 78 | -1.729 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 104 | -2.21 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 104 | -2.24 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 38 | -1.88 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 78 | -2.01 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 52 | -2.25 mg/L |
Secondary
Change From Baseline in Heparan Sulfate Levels in Urine
Change from baseline in Heparan sulfate levels, in g/mol, in urine
Time frame: Weeks 38, 52, 78 and 104
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 38 | -447.2 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 52 | -464.4 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 78 | -512.19 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 104 | -578.89 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 104 | -726.24 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 38 | -692.78 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 78 | -494.610 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Week 52 | -698.79 g/mol |
Secondary
Change From Baseline in Neurocognitive Development Quotient
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
Population: Number of analysed are number of assessments
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Neurocognitive Development Quotient | Week 52 | -8.97 Unitless |
| Dose Group 1 | Change From Baseline in Neurocognitive Development Quotient | Week 104 | -16.28 Unitless |
| Dose Group 2 | Change From Baseline in Neurocognitive Development Quotient | Week 52 | -31.74 Unitless |
| Dose Group 2 | Change From Baseline in Neurocognitive Development Quotient | Week 104 | -24.94 Unitless |
Secondary
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 52 | -17.0 Units on a scale | Standard Deviation 25.9 |
| Dose Group 1 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 104 | -14.5 Units on a scale | Standard Deviation 14.9 |
| Dose Group 2 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 52 | -3.7 Units on a scale | Standard Deviation 24.2 |
| Dose Group 2 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 104 | 0.6 Units on a scale | Standard Deviation 21 |
Secondary
Change From Baseline in PedsQL™ Family Impact Module Total Score
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
Population: Number analysed is available assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | Change From Baseline in PedsQL™ Family Impact Module Total Score | Week 52 | 16.7 Units on a scale | Standard Deviation 12.6 |
| Dose Group 1 | Change From Baseline in PedsQL™ Family Impact Module Total Score | Week 104 | 23.3 Units on a scale | Standard Deviation 31.8 |
| Dose Group 2 | Change From Baseline in PedsQL™ Family Impact Module Total Score | Week 52 | 0.0 Units on a scale | Standard Deviation 0 |
| Dose Group 2 | Change From Baseline in PedsQL™ Family Impact Module Total Score | Week 104 | 0.0 Units on a scale | Standard Deviation 0 |
Secondary
Clearance
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Clearance | Week 78 - central serum | 208 mL/min |
| Dose Group 1 | Clearance | Week 104 - central serum | 1.6 mL/min |
| Dose Group 1 | Clearance | Week 52 - peripheral serum | 3.51 mL/min |
| Dose Group 1 | Clearance | Week 104 - peripheral serum | 2.21 mL/min |
| Dose Group 2 | Clearance | Week 104 - peripheral serum | 3.61 mL/min |
| Dose Group 2 | Clearance | Week 38 - peripheral serum | 0.661 mL/min |
| Unknown | Clearance | Week 78 - peripheral serum | — mL/min |
| Unknown | Clearance | Week 38 - central serum | — mL/min |
| Unknown | Clearance | Week 52 - central serum | — mL/min |
Secondary
Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid
Number of patients in each dose group having anti-drug antibodies cerebrospinal fluid
Time frame: Weeks 52 and 104
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 52 | 2 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 104 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 52 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 104 | 3 Participants |
Secondary
Number of Patients Having Anti-drug Antibodies in Serum
Number of patients in each dose group having anti-drug antibodies in serum
Time frame: Weeks 38, 52, 78 and 104
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Week 38 | 3 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Week 52 | 3 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Week 78 | 3 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Week 104 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Week 104 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Week 38 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Week 78 | 2 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Week 52 | 3 Participants |
Secondary
Pediatric Quality of Life Inventory (PedsQL™) Total Score
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 52 | 53.4 Units on a scale | Standard Deviation 3.9 |
| Dose Group 1 | Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 104 | 55.9 Units on a scale | Standard Deviation 10.2 |
| Dose Group 2 | Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 52 | 72.2 Units on a scale | Standard Deviation 11.6 |
| Dose Group 2 | Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 104 | 76.5 Units on a scale | Standard Deviation 3.8 |
Secondary
PedsQL™ Family Impact Module Total Score
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | PedsQL™ Family Impact Module Total Score | Week 52 | 66.7 Units on a scale | Standard Deviation 30.6 |
| Dose Group 1 | PedsQL™ Family Impact Module Total Score | Week 104 | 73.3 Units on a scale | Standard Deviation 34 |
| Dose Group 2 | PedsQL™ Family Impact Module Total Score | Week 52 | 70.0 Units on a scale | Standard Deviation 26.5 |
| Dose Group 2 | PedsQL™ Family Impact Module Total Score | Week 104 | 70.0 Units on a scale | Standard Deviation 26.5 |
Secondary
SOBI003 Concentration in Cerebrospinal Fluid
Concentration of SOBI003 in cerebrospinal fluid
Time frame: Weeks 52 and 104
Population: Number analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | SOBI003 Concentration in Cerebrospinal Fluid | Week 52 | 15.7 ng/mL |
| Dose Group 1 | SOBI003 Concentration in Cerebrospinal Fluid | Week 104 | 118.35 ng/mL |
| Dose Group 2 | SOBI003 Concentration in Cerebrospinal Fluid | Week 52 | 92.3 ng/mL |
| Dose Group 2 | SOBI003 Concentration in Cerebrospinal Fluid | Week 104 | 57.1 ng/mL |
Secondary
The Half-life
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | The Half-life | Week 38 - central serum | — |
| Unknown | The Half-life | Week 52 - central serum | — |
| Unknown | The Half-life | Week 78 - central serum | — |
| Unknown | The Half-life | Week 104 - central serum | — |
| Unknown | The Half-life | Week 38 - peripheral serum | — |
| Unknown | The Half-life | Week 52 - peripheral serum | — |
| Unknown | The Half-life | Week 78 - peripheral serum | — |
| Unknown | The Half-life | Week 104 - peripheral serum | — |
Secondary
The Maximum Observed Serum Concentration of SOBI003
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 52 - peripheral serum | 45700 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 78 - central serum | 136.0 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 78 - peripheral serum | 195000 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 104 - central serum | 79700 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 104 - peripheral serum | 292500 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 38 - peripheral serum | 7690 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 38 - peripheral serum | 109500 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 104 - peripheral serum | 144000 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 38 - central serum | 105000 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 52 - central serum | 203000 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 78 - central serum | 75.0 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 52 - peripheral serum | 23300 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 78 - peripheral serum | 229500 ng/mL |
Secondary
The Minimum Observed Serum Concentration of SOBI003
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 78 - central serum | 47.0 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 104 - central serum | 2610 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 38 - peripheral serum | 34 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 52 - peripheral serum | 138.5 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 78 - peripheral serum | 362 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 104 - peripheral serum | 704.5 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 78 - peripheral serum | 85 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 38 - central serum | 68.0 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 78 - central serum | 75.0 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 52 - peripheral serum | 25 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 104 - peripheral serum | 75 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 38 - peripheral serum | 30 ng/mL |
Secondary
The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003
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
Population: The table report number of available pharmacokinetic (PK) samples
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 52 - central serum | 7900 ng/mL | — |
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 78 - peripheral serum | 74450 ng/mL | Standard Deviation 105310 |
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 38 - peripheral serum | 14370 ng/mL | Standard Deviation 14583 |
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 104 - central serum | 79700 ng/mL | — |
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 104 - peripheral serum | 292599 ng/mL | Standard Deviation 37477 |
| Dose Group 1 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 52 - peripheral serum | 72000 ng/mL | Standard Deviation 37194 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 104 - peripheral serum | 195000 ng/mL | Standard Deviation 72125 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 38 - peripheral serum | 109500 ng/mL | Standard Deviation 3535.5 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 52 - central serum | 203000 ng/mL | — |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 52 - peripheral serum | 86510 ng/mL | Standard Deviation 122320 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 78 - peripheral serum | 229500 ng/mL | Standard Deviation 101120 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003 | Week 38 - central serum | 210000 ng/mL | — |
Secondary
The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003
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
Population: The table report number of available pharmacokinetic (PK) samples
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Group 1 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 52 - peripheral serum | 123 ng/mL | — |
| Dose Group 1 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 104 - central serum | 2610 ng/mL | — |
| Dose Group 1 | 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 |
| Dose Group 1 | 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 |
| Dose Group 1 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 38 - peripheral serum | 49 ng/mL | — |
| Dose Group 1 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 78 - central serum | 47.0 ng/mL | — |
| Dose Group 2 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 104 - peripheral serum | 66.33 ng/mL | Standard Deviation 49.571 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 78 - central serum | 75.0 ng/mL | — |
| Dose Group 2 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 38 - peripheral serum | 30 ng/mL | Standard Deviation 14.142 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 52 - peripheral serum | 11770 ng/mL | Standard Deviation 16312 |
| Dose Group 2 | The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 38 - central serum | 120.0 ng/mL | — |
Secondary
The Time at Which the Maximum Serum Concentration of SOBI003 is Observed
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 78 - central serum | 168 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 52 - peripheral serum | 5.47 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 52 - central serum | 4.50 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 78 - peripheral serum | 5.88 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 104 - central serum | 4.47 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 104 - peripheral serum | 5.03 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 38 - peripheral serum | 4.5 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 104 - peripheral serum | 12.83 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 52 - central serum | 4.170 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 78 - central serum | 0 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 38 - peripheral serum | 4.825 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 52 - peripheral serum | 7.52 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 78 - peripheral serum | 8.575 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 38 - central serum | 87.96 Hours |
Secondary
The Time of the End of the Infusion of SOBI003
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
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 52- peripheral serum | 4.775 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 104 - central serum | 4.47 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 78- peripheral serum | 4.50 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 38 - peripheral serum | 4.5 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 104- peripheral serum | 5.030 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 52 - central serum | 4.50 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 104- peripheral serum | 8.540 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 52 - central serum | 4.170 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 38 - peripheral serum | 4.825 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 52- peripheral serum | 5.845 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 78- peripheral serum | 8.575 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 38 - central serum | 6.20 Hours |