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

• ClinicalTrials.gov Identifier: NCT02324049
• Recruitment Status: Completed
• First Posted: December 24, 2014
• Results First Posted: July 12, 2018
• Last Update Posted: August 21, 2018
• Sponsor: Alexion
• Information provided by (Responsible Party): Alexion

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis IIIB	Drug: SBC-103	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open Label Study in MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously
• Actual Study Start Date: January 22, 2015
• Actual Primary Completion Date: October 16, 2017
• Actual Study Completion Date: October 16, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: SBC-103; 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; Other Name: recombinant human alpha-N-acetylglucosaminidase

Outcome Measures

Primary Outcome Measures :

1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline to Week 142 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Minnesota

Minneapolis, Minnesota, United States, 55414

United States, Pennsylvania

Pittsburgh, Pennsylvania, United States, 15224

Spain

Barcelona, Spain, 08950

United Kingdom

Birmingham, United Kingdom, B4 6NH

Sponsors and Collaborators

Alexion

  Study Documents (Full-Text)

Documents provided by Alexion:

Study Protocol  [PDF] January 21, 2016

Statistical Analysis Plan  [PDF] September 1, 2017

More Information

• Responsible Party: Alexion
• ClinicalTrials.gov Identifier: NCT02324049
• Other Study ID Numbers: NGLU-CL02
• First Posted: December 24, 2014
• Results First Posted: July 12, 2018
• Last Update Posted: August 21, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion:

Mucopolysaccharidosis type IIIB; Sanfilippo Syndrome; MPS IIIB; Mucopolysaccharidosis; Metabolism, Inborn Errors; Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Connective Tissue Diseases; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Pathologic Processes

Additional relevant MeSH terms:

Mucopolysaccharidoses; Mucopolysaccharidosis III; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases