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

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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:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE December 15, 2014
First Posted Date  ICMJE December 24, 2014
Results First Submitted Date  ICMJE June 12, 2018
Results First Posted Date  ICMJE July 12, 2018
Last Update Posted Date August 21, 2018
Actual Study Start Date  ICMJE January 22, 2015
Actual Primary Completion Date October 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • Incidence of adverse events, serious adverse events, and infusion-associated reactions (IAR)s from baseline [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Changes from baseline in clinical laboratory tests in serum, urine and cerebrospinal fluid [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Changes from baseline in 12-lead electrocardiograms [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Changes in vital signs during and post-infusion, relative to pre-infusion values [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Changes from baseline in physical exam findings [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Changes from baseline in the use of concomitant medications/therapies [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
  • Development of anti-drug antibodies since baseline [ Time Frame: Part A: 24 Weeks; Part B: 128 Weeks and/or 30 days after last study drug infusion in Part B ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • Change from baseline on heparan sulfate in cerebrospinal fluid, blood serum, and urine. [ Time Frame: Baseline to Week 24, Week 28, Week 40, Week 52, Week 66, Week 78, Week 90, Week 104, Week 118, Week 130, Week 142, Week 156 ]
  • The effect of SBC-103 on PK parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    • Serum maximum concentration (Cmax)
    • Time to maximum concentration (Tmax)
    • Area-under-the-concentration-time curve extrapolated to infinity (AUC∞)
    • Half-life (T1/2)
    • Clearance (Cl)
    • Apparent volume of distribution at steady state (Vss)
  • Change from baseline in neurocognitive and developmental function as determined by the scores on select developmental and behavioral assessment tools. [ Time Frame: Baseline to Week 24, Annually up to 3 years ]
  • Changes from baseline in brain structure as assessed by magnetic resonance imaging (MRI). [ Time Frame: Baseline to Week 24, Bi-annually up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB)
Official Title  ICMJE A Phase I/II Open Label Study in MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mucopolysaccharidosis IIIB
Intervention  ICMJE Drug: SBC-103
Other Name: recombinant human alpha-N-acetylglucosaminidase
Study Arms  ICMJE 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.

Intervention: Drug: SBC-103
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 12, 2018)
11
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2014)
9
Actual Study Completion Date  ICMJE October 16, 2017
Actual Primary Completion Date October 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02324049
Other Study ID Numbers  ICMJE NGLU-CL02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP