Phase 2
N=6
A Study to Assess the Safety and Tolerability of SOBI003 in Pediatric MPS IIIA Patients
Sanfilippo Syndrome Type A (MPS IIIA)
Bottom Line
View on ClinicalTrials.gov: NCT03423186 ↗Enrolled (actual)
6
Serious AEs
33.3%
Results posted
Apr 2021
Primary outcome: Primary: Safety as Measured by Adverse Events Frequencies (by Type and Severity) — 53; 128; 0; 1 number of events
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- SOBI003 (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Swedish Orphan Biovitrum
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety as Measured by Adverse Events Frequencies (by Type and Severity) |
53; 128; 0; 1; 53; 124 | — |
| SECONDARY The Observed Serum Concentration Immediately Before the Start of Infusion of SOBI003 |
NA; NA; 58.4; 109.0; 68.85; 135.5 | — |
| SECONDARY The Observed Serum Concentration at the End of Infusion of SOBI003 |
33800; 87500; 34950; 108200; 36750; 82700 | — |
| SECONDARY The Time of the End of the Infusion of SOBI003 |
4.57; 4.33; 4.565; 4.245; 4.28; 4.1 | — |
| SECONDARY The Maximum Observed Serum Concentration of SOBI003 |
33800; 87500; 35700; 77400; 20800; 56900 | — |
| SECONDARY The Time at Which the Maximum Serum Concentration of SOBI003 is Observed |
4.57; 4.33; 4.28; 4.42; 4.23; 6.83 | — |
| SECONDARY The Minimum Observed Serum Concentration of SOBI003 |
NA; NA; 28.9; 115; 26.2; NA | — |
| SECONDARY Clearance |
10.4; 12.8; 8.1; 12.75; 9.5; 13.45 | — |
| SECONDARY Area Under the Serum Concentration-time Curve From Time 0 to 168 Hours |
290044.5; 834411; 369915.5; 789106.5; 324999.5; 749864 | — |
| SECONDARY The Half-life |
19.8; 22.75; 34.3; 7.65; 40.95; 10.75 | — |
| SECONDARY SOBI003 Concentration in Cerebrospinal Fluid |
NA; 17.8; NA; 47.2 | — |
| SECONDARY Number of Patients Having Anti-drug Antibodies in Serum |
1; 1; 2; 3; 3; 3 | — |
| SECONDARY Patients Having Anti-drug Antibodies in Cerebrospinal Fluid |
33.3; 66.7; 66.7; 100 | — |
| SECONDARY Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid |
-5.4; -52.8; -17.5; -50.9 | — |
| SECONDARY Change From Baseline in Heparan Sulfate Levels in Serum |
-1.8070; -1.7460; -1.22; -1.9190; -1.9040; -1.9229 | — |
| SECONDARY Change From Baseline in Heparan Sulfate Levels in Urine |
-456.2; -561.1; -494.67; -597.4; -498.53; -503.465 | — |
| SECONDARY Change From Baseline in Neurocognitive Development Quotient |
-8.7; -15.68 | — |
| SECONDARY Change From Baseline in Age-equivalence Score |
-1.0; -3.0 | — |
| SECONDARY Change From Baseline in Age-equivalence Score as Assessed by VABS-II |
1.0; 0.0 | — |
| SECONDARY Change From Baseline in Gray Matter Volume |
10.858; 39.129 | — |
| SECONDARY Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score |
-9.3; -7.3 | — |
| SECONDARY Change From Baseline in PedsQL™ Family Impact Module Total Score |
-9.77; 1.3 | — |
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).
Eligibility Criteria
Inclusion Criteria
- Informed consent obtained from the patient's legally authorized representative(s)
- 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
Data sourced from ClinicalTrials.gov (NCT03423186). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.