A Study to Assess the Safety and Tolerability of SOBI003 in Pediatric MPS IIIA Patients
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| ClinicalTrials.gov Identifier: NCT03423186 |
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Recruitment Status :
Completed
First Posted : February 6, 2018
Results First Posted : April 22, 2021
Last Update Posted : November 19, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sanfilippo Syndrome Type A (MPS IIIA) | Drug: SOBI003 | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 6 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| 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. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open, Non-controlled, Parallel, Ascending Multiple-dose, Multicenter Study to Assess Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of SOBI003 in Pediatric MPS IIIA Patients |
| Actual Study Start Date : | June 19, 2018 |
| Actual Primary Completion Date : | October 25, 2019 |
| Actual Study Completion Date : | October 25, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose group 1
SOBI003 dose 3 mg/kg once weekly for 24 weeks
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Drug: SOBI003
Weekly i.v.infusion
Other Name: Modified recombinant human sulphamidase |
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Experimental: Dose group 2
SOBI003 dose 10 mg/kg once weekly for 24 weeks
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Drug: SOBI003
Weekly i.v.infusion
Other Name: Modified recombinant human sulphamidase |
- Safety as Measured by Adverse Events Frequencies (by Type and Severity) [ Time Frame: 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
- The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 [ Time Frame: Weeks 1, 2, 3, 4, 8, 12, and 24 ]The observed serum concentration immediately before the start of infusion of SOBI003 (CPre-dose).
- The Observed Serum Concentration at the End of Infusion of SOBI003 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Weeks 1, 4, 12, and 24 ]The minimum observed serum concentration of SOBI003 (CTrough)
- Clearance [ Time Frame: Weeks 1, 4, 12, and 24 ]Clearance (CL) of SOBI003
- Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours [ 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 ]Area under the serum concentration-time curve from time 0 to 168 hours (AUC 0-168h)
- The Half-life [ Time Frame: Weeks 1, 4, 12, and 24 ]The half-life of SOBI003 in serum (T1/2)
- SOBI003 Concentration in Cerebrospinal Fluid [ Time Frame: Weeks 12 and 24 ]SOBI003 concentration in cerebrospinal fluid
- Number of Patients Having Anti-drug Antibodies in Serum [ Time Frame: Weeks 2,4,8,12 and 24 ]Number of patients in each dose group having anti-drug antibodies in serum
- Patients Having Anti-drug Antibodies in Cerebrospinal Fluid [ Time Frame: Weeks 12 and 24 ]Percent of patients having anti-drug antibodies in cerebrospinal fluid
- Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Weeks 2, 3, 4, 8, 12 and 24 ]Change from baseline in Heparan sulfate levels in urine
- Change From Baseline in Neurocognitive Development Quotient [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Months to 72 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Informed consent obtained from the patient's legally authorized representative(s)
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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
- 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)
- Medically stable patient who is expected to be able to comply with study procedures
Exclusion Criteria:
- At least one S298P mutation in the SGSH gene
- Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures
- History of poorly controlled seizures
- Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results
- 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
- Prior administration of stem cell or gene therapy, or ERT for MPS IIIA
- Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03423186
| United States, California | |
| Childrens's Hospital and Research Center | |
| Oakland, California, United States, 94609 | |
| United States, North Carolina | |
| University of North Carolina Hospitals | |
| Chapel Hill, North Carolina, United States, 27599 | |
| Germany | |
| University Medical Center Hamburg-Eppendorf | |
| Hamburg, Germany | |
| Turkey | |
| Gazi University Hospital | |
| Ankara, Turkey | |
| Principal Investigator: | Paul Harmatz, MD | Childrens's Hospital and Research Center Oakland |
Documents provided by Swedish Orphan Biovitrum:
| Responsible Party: | Swedish Orphan Biovitrum |
| ClinicalTrials.gov Identifier: | NCT03423186 |
| Other Study ID Numbers: |
SOBI003-001 |
| First Posted: | February 6, 2018 Key Record Dates |
| Results First Posted: | April 22, 2021 |
| Last Update Posted: | November 19, 2021 |
| Last Verified: | November 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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