Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB)

Study Overview
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Brief Summary
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Study to evaluate the safety and tolerability of intravenous (IV) administration of SBC-103 in participants with mucopolysaccharidosis III, type B (MPS IIIB, Sanfilippo B) with evaluable signs or symptoms of developmental delay.

Detailed Description
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This study was designed as a 3-part study to evaluate the safety and tolerability of IV administration of SBC-103. Participants enrolled in Part A (0.3, 1.0, or 3.0 milligrams [mg] per kilogram [kg] of SBC-103 administered every other week [QOW] for 24 consecutive weeks). Participants who completed Part A were eligible for Part B (an increase to 1.0 or 3.0 mg/kg QOW). Participants who completed Part B were eligible for Part C (5.0 and/or 10.0 mg/kg to continue through Week156; no participants received both 5.0 and 10.0 mg/kg). Due to the early termination of the SBC-103 development program, including this study, all participants withdrew from Part C at the sponsor's decision. As a result of the early termination of this program, this report provides only safety data.

Official Title
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A Phase I/II Open Label Study in MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously

Conditions
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Mucopolysaccharidosis IIIB

Intervention / Treatment
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* Drug: SBC-103


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A participant was greater than or equal to 2 years of age but less than 12 years of age at the time of informed consent. Definitive diagnosis of MPS IIIB. Documented developmental delay. Key Exclusion Criteria: Received treatment with gene therapy at any time. Previous hematopoietic stem cell or bone marrow transplant. Had any internal or non-removable external metal items that presented a safety risk for study assessments that utilized magnetic fields, or any other medical condition or circumstance in which magnetic resonance imaging was contraindicated according to local institutional policy. Known hypersensitivity to eggs.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBC-103<br>Part A (Initial therapy): Participants received SBC-103, 0.3, 1.0, or 3.0 mg/kg QOW for 24 weeks, followed by a ≥ 4-week treatment break. Participants enrolled in the lowest dosage first. Part B: Participants were escalated to the next highest dose that was considered safe (1.0 or 3.0 mg/kg QOW) for ≥ 8 weeks. Participants who received doses of 0.3 mg/kg in Part A were considered for a second dose escalation to 3.0 mg/kg at any time during Part B provided that they tolerated at least 2 doses of 1.0 mg/kg in Part B. Participants who received and tolerated at least 4 doses of SBC-103 QOW at 3.0 mg/kg were considered for participation in Part C. Part C: Participants received SBC-103 5.0 or 10.0 mg/kg administered IV QOW. Dosing in Part C began at the 5.0 mg/kg dose level. The decision to begin dosing the first participant at 10.0 mg/kg was based on the review of safety data at 5.0 mg/kg. | Drug: SBC-103<br> <br> * Other names: recombinant human alpha-N-acetylglucosaminidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event (AE) that occurred after administration of the first dose of study drug on Day 1 (Part A). A severe AE was defined as an AE that was incapacitating and required medical intervention. TEAEs were summarized cumulatively over the entire study and separately for Part C, data for all severe TEAEs throughout the entire study is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Baseline to Week 142 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS IIIB, Mucopolysaccharidosis, Mucopolysaccharidosis type IIIB, Sanfilippo Syndrome, Metabolism, Inborn Errors, Metabolic Diseases, Genetic Diseases, Inborn, Carbohydrate Metabolism, Inborn Errors, Connective Tissue Diseases, Lysosomal Storage Diseases, Mucinoses, Mucopolysaccharidoses, Pathologic Processes