Clinical Trial: A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary: This study is to evaluate the safety and tolerability of intravenous (IV) administration of SBC-103 in previously studied, SBC-103 treatment naïve patients with mucopolysaccharidosis III, type B (MPS IIIB, Sanfilippo B) who participated in the NGLU-CL01 study. The NGLU-CL01 study was a non-interventional study that evaluated structural brain abnormalities and blood brain barrier (BBB) integrity by magnetic resonance imaging (MRI) and cerebrospinal fluid/serum albumin index.

Detailed Summary:
Sponsor: Alexion Pharmaceuticals

Current Primary Outcome: Safety and Tolerability of IV SBC-103 as measured by Physical examinations, vital signs, ECGs, clinical laboratory tests, concomitant medications and development of anti-drug antibodies. [ Time Frame: Baseline to Week 156 ]

Original Primary Outcome:

  • Incidence of adverse events (AEs), serious adverse events (SAEs), and infusion-associated reactions (IARs); [ Time Frame: 30 days after the last study drug infusion ]
  • Changes from baseline in clinical laboratory tests (hematology, serum chemistry, and urinalysis) and CSF (cerebrospinal fluid) findings (cell counts, glucose, and protein) [ Time Frame: 30 days after the last study drug infusion ]
  • Changes from baseline in 12-lead electrocardiograms [ Time Frame: 30 days after the last study drug infusion ]
  • Changes in vital signs during and post-infusion, relative to pre-infusion values [ Time Frame: 30 days after the last study drug infusion ]
  • Physical examination findings [ Time Frame: 30 days after the last study drug infusion ]
  • Use of concomitant medications/therapies [ Time Frame: 30 days after the last study drug infusion ]
  • Assessment of anti-drug antibodies (ADAs) [ Time Frame: 30 days after the last study drug infusion ]


Current Secondary Outcome: PK/PD effects of SBC 103 after single and multiple IV doses, neurocognitive and developmental function, brain structure volumetric assessment, indices of microstructural integrity, and BBB integrity. [ Time Frame: Baseline to Week 156 ]

Original Secondary Outcome:

  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Serum maximum concentration (Cmax)
  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Time to maximum concentration (Tmax)
  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Area-under-the-concentration-time curve extrapolated to infinity (AUC∞)
  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Half-life (T1/2)
  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Clearance (Cl)
  • Effect of SBC-103 on pharmacokinetic (PK) parameters [ Time Frame: Week 0, Week 12, Week 24, Week 52, Week 78, Week 104, Week 130, Week 156 ]
    Apparent volume of distribution at steady state (Vss)
  • Changes in levels of heparan sulfate (HS) during the observational period and the treatment period with IV SBC-103 [ Time Frame: Baseline to Week 12, Week 24, Week 36, Week 52, Week 68, Week 78, Week 90, Week 104, Week 120, Week 130, Week 142,Week 156 ]
  • Neurocognitive and developmental function during the observational period and following dosing with SBC-103 [ Time Frame: Baseline to Week 24, annually up to 3 years ]
  • Changes in brain structure during the observational period and following dosing with SBC-103 as determined by the relative proportion of grey and white matter volume and indices of microstructural integrity as assessed by magnetic resonance imaging (MRI) [ Time Frame: Baseline to Week 24, bi-annually up to 3 years ]
  • Changes in blood-brain barrier (BBB) integrity during the observational period and following dosing with SBC-103 as determined by cerebrospinal fluid-albumin (CSF-AI). [ Time Frame: Baseline to Week 12, Week 24, Week 36, Week 52, Week 68, Week 78, Week 90, Week 104, Week 120, Week 130, Week 142,Week 156 ]


Information By: Alexion Pharmaceuticals

Dates:
Date Received: October 21, 2015
Date Started: September 2015
Date Completion: December 2018
Last Updated: August 4, 2016
Last Verified: August 2016