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Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis (rhLaman-08)

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ClinicalTrials.gov Identifier: NCT02998879
Recruitment Status : Completed
First Posted : December 21, 2016
Last Update Posted : October 26, 2021
Sponsor:
Collaborator:
Cromsource
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.

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

Condition or disease Intervention/treatment Phase
Alpha-Mannosidosis Drug: Velmanase Alfa (e.g. Lamazym) Phase 2

Detailed Description:

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 tissue, MRI
  • Pharmacokinetic parameters

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 of Age With Alpha-Mannosidosis
Study Start Date : December 2016
Actual Primary Completion Date : July 2020
Actual Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Velmanase Alfa
velmanase alfa 1mg/kg body weight infusion
Drug: Velmanase Alfa (e.g. Lamazym)
iv infusion treatment
Other Name: Lamazym




Primary Outcome Measures :
  1. 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]

  2. Safety and tolerability of velmanase alfa as per vital signs [ Time Frame: From baseline throughout study completion, at least of 2 years ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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 ]
  4. Functional capacity: Mullen Scales of Early Learning (MSEL) [ Time Frame: From baseline throughout study completion, at least for 2 years ]
  5. 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 ]
  6. 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 ]
  7. Hearing evaluation: Otoacoustic Emissions (OAE) testing [ Time Frame: From baseline throughout study completion, at least for 2 years ]
  8. Hearing evaluation: Automatic Auditory Brainstem Response (A-ABR) audiometry [ Time Frame: From baseline throughout study completion, at least for 2 years ]
  9. 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 ]
  10. 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 ]
  11. Assessment of quality of life via Questionnaire [ Time Frame: From baseline throughout study completion, at least for 2 years ]
  12. 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 ]
  13. 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 ]
  14. Pharmacokinetic parameters to determine Cmax (Peak Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  15. Pharmacokinetic parameters to determine Ctrough (Trough Plasma Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  16. Pharmacokinetic parameters to determine Area Under Curve (AUC24) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  17. 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) ]
  18. 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) ]
  19. Pharmacokinetic parameters to determine tmax (Time To Peak Concentration) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  20. Pharmacokinetic parameters to determine CL (Clearance) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  21. Pharmacokinetic parameters to determine t1/2 (Elimination Half-Life) [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]
  22. Pharmacokinetic parameters to determine Rac (Obs) Observed Accumulation Ratio [ Time Frame: At first dose (visit 1) and after 6 months (visit 26) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient's custodial parent(s) must provide signed ICF prior to the involvement of the patient in any trial-related activities
  2. The subject's custodial parent(s) must have the ability to comply with the protocol
  3. The subject must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity in leukocytes or fibroblasts < 10% of normal activity (historical data)
  4. The subject must have an age at the time of screening < 6 years.

Exclusion Criteria:

  1. The subject's diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
  2. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
  3. History of BMT
  4. Presence of known clinically significant cardiovascular, hepatic, pulmonary, or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
  5. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
  6. Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
  7. Participation in other interventional trials testing the IMP within the last 3 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02998879


Locations
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Austria
Wien, Austria
Denmark
Copenhagen, Denmark
France
Lyon, France
Germany
Hamburg, Germany
Mainz, Germany
Italy
Trieste, Italy
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Cromsource
Additional Information:
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Responsible Party: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT02998879    
Other Study ID Numbers: CCD-LMZYMAA1-08
2016-001988-36 ( EudraCT Number )
First Posted: December 21, 2016    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Mannosidase Deficiency Diseases
alpha-Mannosidosis
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases