Mucopolysaccharidosis IIIB
Conditions
Keywords
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
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.
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.
Interventions
DRUGSBC-103
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 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. |
Countries
Spain, United Kingdom, United States
Participant flow
Recruitment details
Diagnosis of mucopolysaccharidosis III, type B (MPS IIIB), determined by either documented deficiency in Alpha-N-acetylglucosaminidase (NAGLU) enzyme activity ≤10% of the mean value in normal individuals at Screening OR documented functionally-relevant mutations in both alleles of the NAGLU gene based on historical or Screening laboratory results.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part C | Study terminated | 11 |
Baseline characteristics
| Characteristic | SBC-103 |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Overall Age at Diagnosis 10.0 mg/kg | 25.0 Months |
| Overall Age at Diagnosis 5.0 mg/kg | 48.0 Months |
| Overall Age at Diagnosis Overall | 37.0 Months |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 3 / 11 |
Outcome results
Primary
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.
Time frame: Baseline to Week 142
Population: Safety Population: all participants for whom informed consent had been obtained, who had a confirmed diagnosis of MPS IIIB, and who had received any amount of SBC-103.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SBC-103 | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 5.0 mg/kg | 1 Participants |
| SBC-103 | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 10.0 mg/kg | 0 Participants |
| SBC-103 | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | Overall | 1 Participants |