Clinical Trial: Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years o

Brief Summary: The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years

Detailed Summary:

The Primary endpoints of the study include:

  • Safety and tolerability of velmanase alfa as per Adverse events (AEs, including IRR), vital signs, laboratory parameters (hematology, biochemistry and urinanalysis)
  • Detection of anti-velmanase alfa antibodies and neutralizing/inhibitory antibodies

The Secondary endpoints include changes from baseline to 24 months for the following parameters. Efficacy outcomes:

  • Serum oligosaccharides
  • Functional capacity: Peabody Developmental Motor Scale - 2nd edition (PDMS-2) scores, Mullen's Scale of Early Learning (MSEL) scores, Bruininks-Oseretsky Test Of Motor Proficiency-2nd Edition (BOT-2), when applicable by age (from 4 years) or upon the judgment of the physician
  • Endurance: 3-Minute Stair Climb Test (3MSCT) and 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician, 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age, or when applicable according to the judgment of the physician
  • Hearing evaluation: Otoacoustic Emissions (OAE) testing, Automatic Auditory Brainstem Response (A-ABR) audiometry
  • Immunological profile, when applicable upon the judgment of the physician:
  • CSF biomarkers: Tau protein (Tau), Neurofilament Protein Light (NFL), Glial Fibrillary Acidic Protein (GFAp), Oligosaccharides
  • Assessment of quality of life via Questionnaire to parents
  • Assessment of mannose-rich oligosaccharides in brain tiss
    Sponsor: Chiesi Farmaceutici S.p.A.

    Current Primary Outcome:

    • Safety and tolerability of velmanase alfa as per Adverse events [ Time Frame: From baseline throughout study completion, at least of 2 years ]
      Safety and tolerability assessed as per AEs including infusion-related reactions [IRRs]
    • Safety and tolerability of velmanase alfa as per vital signs [ Time Frame: From baseline throughout study completion, at least of 2 years ]
    • Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per hematology [ Time Frame: From baseline throughout study completion, at least of 2 years ]
    • Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per blood biochemistry [ Time Frame: From baseline throughout study completion, at least of 2 years ]
    • Safety and tolerability of velmanase alfa as per clinical laboratory parameters as per urinalysis [ Time Frame: From baseline throughout study completion, at least of 2 years ]
    • Detection of anti-velmanase alfa-IgG antibodies (ADA) and neutralizing/inhibitory antibodies [ Time Frame: From baseline throughout study completion, at least of 2 years ]
      Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Evaluation of levels of Serum oligosaccharides [ Time Frame: From baseline throughout study completion, at least for 2 years ]
      Assessment of change from baseline in levels of Serum oligosaccharides
    • Functional capacity: The Peabody Developmental Motor Scale test (PDMS-2) [ Time Frame: From baseline throughout study completion, at least for 2 years ]
      Serum samples for anti-velmanase alfa-IgG antibody (ADA) testing will be obtained
    • Functional capacity: Bruininks-Oseretsky test of Motor Proficiency (BOT-2) when applicable by age (from 4 years) or upon the judgment of the physician [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Functional capacity: Mullen Scales of Early Learning (MSEL) [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Endurance: 3-Minute Stair Climb Test (3MSCT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Endurance: 6-Minute Walk Test (6MWT) in pediatric patients from 4 years of age, or when applicable according to the judgment of the physician 2-Minute Walk Test (2MWT) in pediatric patients below 4 years of age [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Hearing evaluation: Otoacoustic Emissions (OAE) testing [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Immunological profile when applicable upon the judgement of the physician (Serum IgG, IgA, IgM; in vitro synthesis of IgG; in vitro proliferative response and Immunophenotype) [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • CSF biomarkers: Tau protein (Tau) § Neurofilament Protein Light (NFL) § Glial Fibrillary Acidic Protein (GFAp) § Oligosaccharides [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Assessment of quality of life via Questionnaire [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Assessment of mannose-rich oligosaccharides in brain tissue, as measured by Magnetic Resonance Spectroscopy (MRS) [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Magnetic Resonance Imaging (MRI) in white matter, gray matter and in centrum semi ovale, and diffusion-MRI of the brain, [ Time Frame: From baseline throughout study completion, at least for 2 years ]
    • Pharmacokinetic parameters to determine Cmax (Peak Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine Area Under Curve (AUC24) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine AUClast (Area Under Curve After The Last Count) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine AUCinf (Area Under Curve From Time Zero To Infinity) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine tmax (Time To Peak Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine CL (Clearance) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
    • Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]


    Original Secondary Outcome: Same as current

    Information By: Chiesi Farmaceutici S.p.A.

    Dates:
    Date Received: November 25, 2016
    Date Started: December 2016
    Date Completion: February 2020
    Last Updated: January 11, 2017
    Last Verified: January 2017