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 aims of the present study is to assess the dose related safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SOBI003, a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).
Detailed description
This is an open-label, non-controlled, parallel, sequential ascending multiple-dose, multicenter study to assess the dose related safety, tolerability, PK and PD of SOBI003 in pediatric MPS IIIA patients. Patients between 1 and 6 years of age who have not received previous treatment for MPS IIIA with an ERT, gene- or stem cell therapy will be eligible to participate in the study. The study is planned to consist of 3 dose cohorts, each comprising 3 patients. Treatment initiations will be staggered within each cohort in order to be able to observe, interpret and treat possible adverse reactions. SOBI003 is administered as weekly i.v. infusions over a period of 24 weeks. Upon completion of the 24-week treatment period with satisfactory tolerability, the patient is offered to receive continued SOBI003 treatment by participation in an extension study.
Interventions
DRUGSOBI003
Weekly i.v.infusion
Sponsors
Swedish Orphan Biovitrum
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study was designed to include three arms, up to 20 mg/kg. After a company decision to end the development of the compound it was decided to not start a third cohort, but if stated safe the dose could increase up to 20 mg/kg in cohort 1 and 2.
Eligibility
Sex/Gender
ALL
Age
12 Months to 72 Months
Healthy volunteers
No
Inclusion criteria
1. Informed consent obtained from the patient's legally authorized representative(s) 2. Patients with MPS IIIA, as confirmed by both: * A documented deficiency in sulfamidase enzyme activity in concordance with a diagnosis of MPS IIIA, and * Normal enzyme activity level of at least one other sulfatase measured in leukocytes 3. Chronological age of ≥12 and ≤72 months (i.e., 1 to 6 years) at the time of the first SOBI003 infusion and a developmental age ≥12 months at screening as assessed by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) 4. Medically stable patient who is expected to be able to comply with study procedures
Exclusion criteria
1. At least one S298P mutation in the SGSH gene 2. Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures 3. History of poorly controlled seizures 4. Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results 5. Significant non-MPS IIIA-related central nervous system (CNS) impairment or behavioral disturbances, which in the investigator's opinion, would confound the scientific integrity or interpretation of study assessments 6. Prior administration of stem cell or gene therapy, or ERT for MPS IIIA 7. Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Measured by Adverse Events Frequencies (by Type and Severity) | From start of first infusion up to Week 24 | Number of adverse events, by type and severity, from start of infusion up to 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Observed Serum Concentration at the End of Infusion of SOBI003 | Weeks 1, 2, 3, 4, 8, 12, and 24 | The observed serum concentration at the end of infusion of SOBI003 (CEnd of inf) |
| The Time of the End of the Infusion of SOBI003 | Weeks 1, 2, 3, 4, 8, 12, and 24 | The time of the end of infusion of SOBI003 (tEnd of inf) |
| The Maximum Observed Serum Concentration of SOBI003 | 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Weeks 1, 4, 12, and 24 | The Maximum Observed Serum Concentration of SOBI003 (Cmax) |
| The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Weeks 1, 4, 12, and 24 | The time after start of infusion at which the maximum serum concentration is observed (tmax) |
| The Minimum Observed Serum Concentration of SOBI003 | Weeks 1, 4, 12, and 24 | The minimum observed serum concentration of SOBI003 (CTrough) |
| Clearance | Weeks 1, 4, 12, and 24 | Clearance (CL) of SOBI003 |
| Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | 0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 1, 4,12, and 24 | Area under the serum concentration-time curve from time 0 to 168 hours (AUC 0-168h) |
| The Half-life | Weeks 1, 4, 12, and 24 | The half-life of SOBI003 in serum (T1/2) |
| SOBI003 Concentration in Cerebrospinal Fluid | Weeks 12 and 24 | SOBI003 concentration in cerebrospinal fluid |
| Number of Patients Having Anti-drug Antibodies in Serum | Weeks 2,4,8,12 and 24 | Number of patients in each dose group having anti-drug antibodies in serum |
| The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Weeks 1, 2, 3, 4, 8, 12, and 24 | The observed serum concentration immediately before the start of infusion of SOBI003 (CPre-dose). |
| Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid | Baseline, weeks 12, and 24 | Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid |
| Change From Baseline in Heparan Sulfate Levels in Serum | Weeks 2, 3, 4, 8, 12 and 24 | Change from baseline in Heparan sulfate levels in serum |
| Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 2, 3, 4, 8, 12 and 24 | Change from baseline in Heparan sulfate levels in urine |
| Change From Baseline in Neurocognitive Development Quotient | Week 24 | Quotient between age equivalent score and age, 0 - 100%, where high values are desirable. The age equivalent score represent the age of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development. |
| Change From Baseline in Age-equivalence Score | Week 24 | The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by the Bayley Scales of Infant and Toddler Development®, third edition cognitive subtest or the Kaufman Assessment Battery for Children, Second edition. The Bayley Scales of Infant and Toddler Development-Third Edition is an individually administered test designed to assess developmental functioning of infants and toddlers. The Bayley-III assesses development in five areas: cognitive, language, motor, social-emotional, and adaptive behavior. The Kaufman Assessment Battery for Children (K-ABC) is a clinical instrument for assessing cognitive development. |
| Change From Baseline in Age-equivalence Score as Assessed by VABS-II | Week 24 | The age equivalent score represent the age in months of the typical and normal individual who would achieve the same result as the one who was tested. The age equivalent scores are assessed by Vineland™ Adaptive Behavior Scales, Expanded Interview Form, Second edition (VABS-II). The Vineland is designed to measure adaptive behavior of individuals from birth to age 90. The Vineland-II contains 5 domains each with 2-3 subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior. |
| Change From Baseline in Gray Matter Volume | Week 24 | Grey matter contains most of the brain's neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, and sensory perception such as seeing and hearing, memory, emotions, speech, decision making, and self-control. The gray matter volume will be measured by volumetric magnetic resonance imaging (MRI). |
| Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | Week 24 | Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Lower scores indicate better functioning. Min score = 0, and max score = 144. |
| Change From Baseline in PedsQL™ Family Impact Module Total Score | Week 24 | Pediatric Quality of Life Inventory (PedsQL™) is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The measure includes a scale, from where the categorical score 4, 3, 2, 1, and 0 was reversed and linearly transformed to a 0-100 scale to 4=0, 3=25, 2=50, 1=75 and 0=100, where 100 = minimum and 0 = maximum. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning. |
| Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Weeks 12 and 24 | Percent of patients having anti-drug antibodies in cerebrospinal fluid |
Countries
Germany, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Group 1 SOBI003 dose 3 mg/kg once weekly for 24 weeks
SOBI003: Weekly i.v.infusion | 3 |
| Dose Group 2 SOBI003 dose 10 mg/kg once weekly for 24 weeks
SOBI003: Weekly i.v.infusion | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Dose Group 2 | Total | Dose Group 1 |
|---|---|---|---|
| Age, Continuous | 29.0 months STANDARD_DEVIATION 12.2 | 37.7 months STANDARD_DEVIATION 19.6 | 46.3 months STANDARD_DEVIATION 24.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 1 / 3 | 1 / 3 |
Outcome results
Primary
Safety as Measured by Adverse Events Frequencies (by Type and Severity)
Number of adverse events, by type and severity, from start of infusion up to 24 weeks
Time frame: From start of first infusion up to Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious drug-related TEAE | 0 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-treatment emergent serious adverse event | 0 number of 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 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE | 27 number of 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 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-serious TEAE | 52 number of 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 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any adverse event | 53 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to death | 0 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE | 1 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any Infusion related Reaction | 17 number of events |
| Dose Group 1 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any treatment emergent adverse event (TEAE) | 53 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any Infusion related Reaction | 27 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any treatment emergent adverse event (TEAE) | 124 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any adverse event | 128 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any drug-related TEAE | 74 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-serious TEAE | 121 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious TEAE | 3 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any serious drug-related TEAE | 0 number of 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 number of 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 number of 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 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any TEAE leading to death | 0 number of events |
| Dose Group 2 | Safety as Measured by Adverse Events Frequencies (by Type and Severity) | Any non-treatment emergent serious adverse event | 1 number of events |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours
Area under the serum concentration-time curve from time 0 to 168 hours (AUC 0-168h)
Time frame: 0,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Weeks 1, 4,12, and 24
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 1 | 290044.5 h*ng/mL |
| Dose Group 1 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 4 | 369915.5 h*ng/mL |
| Dose Group 1 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 12 | 324999.5 h*ng/mL |
| Dose Group 1 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 24 | 198973 h*ng/mL |
| Dose Group 2 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 24 | 961516.5 h*ng/mL |
| Dose Group 2 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 1 | 834411 h*ng/mL |
| Dose Group 2 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 12 | 749864 h*ng/mL |
| Dose Group 2 | Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours | Week 4 | 789106.5 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 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Change From Baseline in Age-equivalence Score | -1.0 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score | -3.0 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 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | 1.0 Months |
| Dose Group 2 | Change From Baseline in Age-equivalence Score as Assessed by VABS-II | 0.0 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).
Time frame: Week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Change From Baseline in Gray Matter Volume | 10.858 mL |
| Dose Group 2 | Change From Baseline in Gray Matter Volume | 39.129 mL |
Secondary
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid
Change from baseline, in percent, of Heparan Sulfate levels in cerebrospinal fluid
Time frame: Baseline, weeks 12, and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid | Week 12 | -5.4 percent change |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid | Week 24 | -17.5 percent change |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid | Week 12 | -52.8 percent change |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid | Week 24 | -50.9 percent change |
Secondary
Change From Baseline in Heparan Sulfate Levels in Serum
Change from baseline in Heparan sulfate levels in serum
Time frame: Weeks 2, 3, 4, 8, 12 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 4 | -1.9040 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 2 | -1.8070 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 8 | -2.1030 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 3 | -1.22 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 24 | -1.7480 mg/L |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 12 | -1.8170 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 24 | -1.8310 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 3 | -1.9190 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 4 | -1.9229 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 12 | -1.8340 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 8 | -1.8290 mg/L |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Serum | Week 2 | -1.7460 mg/L |
Secondary
Change From Baseline in Heparan Sulfate Levels in Urine
Change from baseline in Heparan sulfate levels in urine
Time frame: Weeks 2, 3, 4, 8, 12 and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 8 | -474.7 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 12 | -534.1 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 24 | -421.98 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 2 | -456.2 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 3 | -494.67 g/mol |
| Dose Group 1 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 4 | -498.53 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 24 | -695.9 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 4 | -503.465 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 8 | -666.81 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 3 | -597.4 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 12 | -640.2 g/mol |
| Dose Group 2 | Change From Baseline in Heparan Sulfate Levels in Urine | Weeks 2 | -561.1 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.
Time frame: Week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Change From Baseline in Neurocognitive Development Quotient | -8.7 unitless |
| Dose Group 2 | Change From Baseline in Neurocognitive Development Quotient | -15.68 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. Lower scores indicate better functioning. Min score = 0, and max score = 144.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | -9.3 Units on a scale | Standard Deviation 15.52 |
| Dose Group 2 | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score | -7.3 Units on a scale | Standard Deviation 14.9 |
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 measure includes a scale, from where the categorical score 4, 3, 2, 1, and 0 was reversed and linearly transformed to a 0-100 scale to 4=0, 3=25, 2=50, 1=75 and 0=100, where 100 = minimum and 0 = maximum. The Total Score is the sum of all 36 items in the test divided by the number of items answered. Higher scores indicate better functioning.
Time frame: Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Group 1 | Change From Baseline in PedsQL™ Family Impact Module Total Score | -9.77 Units on a scale | Standard Deviation 19.05 |
| Dose Group 2 | Change From Baseline in PedsQL™ Family Impact Module Total Score | 1.3 Units on a scale | Standard Deviation 3.11 |
Secondary
Clearance
Clearance (CL) of SOBI003
Time frame: Weeks 1, 4, 12, and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | Clearance | Week 24 | 19.5 (mL/h)/kg |
| Dose Group 1 | Clearance | Week 1 | 10.4 (mL/h)/kg |
| Dose Group 1 | Clearance | Week 4 | 8.1 (mL/h)/kg |
| Dose Group 1 | Clearance | Week 12 | 9.5 (mL/h)/kg |
| Dose Group 2 | Clearance | Week 12 | 13.45 (mL/h)/kg |
| Dose Group 2 | Clearance | Week 24 | 10.4 (mL/h)/kg |
| Dose Group 2 | Clearance | Week 4 | 12.75 (mL/h)/kg |
| Dose Group 2 | Clearance | Week 1 | 12.8 (mL/h)/kg |
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 2,4,8,12 and 24
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 4 | 2 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 8 | 3 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 12 | 3 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 2 | 1 Participants |
| Dose Group 1 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 24 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 24 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 4 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 2 | 1 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 8 | 3 Participants |
| Dose Group 2 | Number of Patients Having Anti-drug Antibodies in Serum | Weeks 12 | 3 Participants |
Secondary
Patients Having Anti-drug Antibodies in Cerebrospinal Fluid
Percent of patients having anti-drug antibodies in cerebrospinal fluid
Time frame: Weeks 12 and 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Group 1 | Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 12 | 33.3 percent of participants in dose group |
| Dose Group 1 | Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 24 | 66.7 percent of participants in dose group |
| Dose Group 2 | Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 12 | 66.7 percent of participants in dose group |
| Dose Group 2 | Patients Having Anti-drug Antibodies in Cerebrospinal Fluid | Week 24 | 100 percent of participants in dose group |
Secondary
SOBI003 Concentration in Cerebrospinal Fluid
SOBI003 concentration in cerebrospinal fluid
Time frame: Weeks 12 and 24
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | SOBI003 Concentration in Cerebrospinal Fluid | Week 12 | NA mg/L |
| Dose Group 1 | SOBI003 Concentration in Cerebrospinal Fluid | Week 24 | NA mg/L |
| Dose Group 2 | SOBI003 Concentration in Cerebrospinal Fluid | Week 12 | 17.8 mg/L |
| Dose Group 2 | SOBI003 Concentration in Cerebrospinal Fluid | Week 24 | 47.2 mg/L |
Secondary
The Half-life
The half-life of SOBI003 in serum (T1/2)
Time frame: Weeks 1, 4, 12, and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Half-life | Week 1 | 19.8 Hours |
| Dose Group 1 | The Half-life | Week 4 | 34.3 Hours |
| Dose Group 1 | The Half-life | Week 12 | 40.95 Hours |
| Dose Group 1 | The Half-life | Week 24 | 20.85 Hours |
| Dose Group 2 | The Half-life | Week 24 | 15.95 Hours |
| Dose Group 2 | The Half-life | Week 1 | 22.75 Hours |
| Dose Group 2 | The Half-life | Week 12 | 10.75 Hours |
| Dose Group 2 | The Half-life | Week 4 | 7.65 Hours |
Secondary
The Maximum Observed Serum Concentration of SOBI003
The Maximum Observed Serum Concentration of SOBI003 (Cmax)
Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Weeks 1, 4, 12, and 24
Population: Samples was taken centrally and/or peripherally.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 12 | 20800 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 24 | 17500 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 1 | 33800 ng/mL |
| Dose Group 1 | The Maximum Observed Serum Concentration of SOBI003 | Week 4 | 35700 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 24 | 93500 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 4 | 77400 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 12 | 56900 ng/mL |
| Dose Group 2 | The Maximum Observed Serum Concentration of SOBI003 | Week 1 | 87500 ng/mL |
Secondary
The Minimum Observed Serum Concentration of SOBI003
The minimum observed serum concentration of SOBI003 (CTrough)
Time frame: Weeks 1, 4, 12, and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 1 | NA ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 4 | 28.9 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 12 | 26.2 ng/mL |
| Dose Group 1 | The Minimum Observed Serum Concentration of SOBI003 | Week 24 | 44.8 ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 24 | NA ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 1 | NA ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 12 | NA ng/mL |
| Dose Group 2 | The Minimum Observed Serum Concentration of SOBI003 | Week 4 | 115 ng/mL |
Secondary
The Observed Serum Concentration at the End of Infusion of SOBI003
The observed serum concentration at the end of infusion of SOBI003 (CEnd of inf)
Time frame: Weeks 1, 2, 3, 4, 8, 12, and 24
Population: Number of analysed are available samples
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 3 | 36750 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 8 | 20800 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 2 | 34950 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 12 | 30500 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 4 | 35700 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 24 | 17500 ng/mL |
| Dose Group 1 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 1 | 33800 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 24 | 93500 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 1 | 87500 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 2 | 108200 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 3 | 82700 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 4 | 77400 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 8 | 50900 ng/mL |
| Dose Group 2 | The Observed Serum Concentration at the End of Infusion of SOBI003 | Week 12 | 56900 ng/mL |
Secondary
The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003
The observed serum concentration immediately before the start of infusion of SOBI003 (CPre-dose).
Time frame: Weeks 1, 2, 3, 4, 8, 12, and 24
Population: The table report number of available pharmacokinetic (PK) samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 3 | 68.85 ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 8 | NA ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 2 | 58.4 ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 12 | 33.75 ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 4 | 71.4 ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 24 | NA ng/mL |
| Dose Group 1 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 1 | NA ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 24 | 16.4 ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 1 | NA ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 2 | 109.0 ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 3 | 135.5 ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 4 | 49.8 ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 8 | 25.5 ng/mL |
| Dose Group 2 | The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 | Week 12 | NA 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)
Time frame: Weeks 1, 4, 12, and 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 4 | 4.28 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 1 | 4.57 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 12 | 4.23 Hours |
| Dose Group 1 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 24 | 4.45 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 24 | 4.75 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 4 | 4.42 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 12 | 6.83 Hours |
| Dose Group 2 | The Time at Which the Maximum Serum Concentration of SOBI003 is Observed | Week 1 | 4.33 Hours |
Secondary
The Time of the End of the Infusion of SOBI003
The time of the end of infusion of SOBI003 (tEnd of inf)
Time frame: Weeks 1, 2, 3, 4, 8, 12, and 24
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 3 | 4.28 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 8 | 4.85 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 2 | 4.565 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 12 | 4.23 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 4 | 4.28 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 24 | 4.45 Hours |
| Dose Group 1 | The Time of the End of the Infusion of SOBI003 | Week 1 | 4.57 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 24 | 4.75 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 1 | 4.33 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 2 | 4.245 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 3 | 4.1 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 4 | 4.42 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 8 | 8.17 Hours |
| Dose Group 2 | The Time of the End of the Infusion of SOBI003 | Week 12 | 6.83 Hours |