Clinical trial NCT03811028: A Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients
Official title: An Open, Single-arm, Multicenter Extension Study to Assess the Safety, Tolerability, and Efficacy of Long-term SOBI003 Treatment in Pediatric MPS IIIA Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sanfilippo Syndrome Type A (MPS IIIA)
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety as Measured by Adverse Events Frequencies (by Type and Severity)
timeFrame: From infusion week 25 up to week 104
Secondary outcomes:
measure: The Observed SOBI003 Serum Concentration Immediately Before the Start of Infusion of SOBI003
timeFrame: Weeks 38, 52, 78 and 104
measure: The Observed SOBI003 Serum Concentration at the End of Infusion of SOBI003
timeFrame: Weeks 38, 52, 78 and 104
measure: The Time of the End of the Infusion of SOBI003
timeFrame: Weeks 38, 52, 78 and 104
measure: The Maximum Observed Serum Concentration of SOBI003
timeFrame: Weeks 38, 52, 78 and 104
measure: The Time at Which the Maximum Serum Concentration of SOBI003 is Observed
timeFrame: Weeks 38, 52, 78 and 104
measure: The Minimum Observed Serum Concentration of SOBI003
timeFrame: Weeks 38, 52, 78 and 104
measure: Clearance
timeFrame: Weeks 38, 52, 78 and 104
measure: Area Under the SOBI003 Serum Concentration-time Curve From Time 0 to168 Hours
timeFrame: 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
measure: The Half-life
timeFrame: Weeks 38, 52, 78 and 104
measure: SOBI003 Concentration in Cerebrospinal Fluid
timeFrame: Weeks 52 and 104
measure: Number of Patients Having Anti-drug Antibodies in Serum
timeFrame: Weeks 38, 52, 78 and 104
measure: Number of Patients Having Anti-drug Antibodies in Cerebrospinal Fluid
timeFrame: Weeks 52 and 104
measure: Change From Baseline in Heparan Sulfate Concentration in Cerebrospinal Fluid
timeFrame: Weeks 52 and 104
measure: Change From Baseline in Heparan Sulfate Levels in Serum
timeFrame: Weeks 38, 52, 78 and 104
measure: Change From Baseline in Heparan Sulfate Levels in Urine
timeFrame: Weeks 38, 52, 78 and 104
measure: Change From Baseline in Neurocognitive Development Quotient
timeFrame: Weeks 52 and 104
measure: Change From Baseline in Age-equivalence Score
timeFrame: Week 52 and 104
measure: Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
timeFrame: Week 52 and 104
measure: Change From Baseline in Age-equivalence Score as Assessed Either by the BSID-III, Cognitive Subtest, or the KABC-II.
timeFrame: Week 52 and 104
measure: Age-equivalence Score as Assessed by VABS-II
timeFrame: Week 52 and 104
measure: Change From Baseline in Age-equivalence Score as Assessed by VABS-II
timeFrame: Week 52 and 104
measure: Change From Baseline in Gray Matter Volume
timeFrame: Week 52 and 104
measure: Pediatric Quality of Life Inventory (PedsQL™) Total Score
timeFrame: Week 52 and 104
measure: Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Total Score
timeFrame: Week 52 and 104
measure: PedsQL™ Family Impact Module Total Score
timeFrame: Week 52 and 104
measure: Change From Baseline in PedsQL™ Family Impact Module Total Score
timeFrame: Week 52 and 104
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children´s Hospital and research center
state: California
city: Chapel Hill
country: United States
facility: University of North Carolina hospitals
state: North Carolina
city: Ankara
country: Turkey
facility: Gazi University Hospital
Study officials:
affiliation: Children´s Hospital and Research Center, Oakland
name: Paul Harmatz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harmatz P, Muenzer J, Ezgu F, Dalen P, Huledal G, Lindqvist D, Gelius SS, Wiken M, Onnestam K, Broijersen A. Chemically modified recombinant human sulfamidase (SOBI003) in mucopolysaccharidosis IIIA patients: Results from an open, non-controlled, multicenter study. Mol Genet Metab. 2022 Aug;136(4):249-259. doi: 10.1016/j.ymgme.2022.06.008. Epub 2022 Jun 28.