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

Brief Title

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

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

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 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
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Safety and tolerability of velmanase alfa as per Adverse events

Secondary Outcome

 Evaluation of levels of Serum oligosaccharides

Condition

Alpha-Mannosidosis

Intervention

Velmanase Alfa (e.g. Lamazym)

Study Arms / Comparison Groups

 Velmanase Alfa
Description:  velmanase alfa 1mg/kg body weight infusion

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

5

Start Date

December 2016

Completion Date

July 2020

Primary Completion Date

July 2020

Eligibility 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.
      

Gender

All

Ages

N/A - 6 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT02998879

Organization ID

CCD-LMZYMAA1-08

Secondary IDs

2016-001988-36

Responsible Party

Sponsor

Study Sponsor

Chiesi Farmaceutici S.p.A.

Collaborators

 Cromsource

Study Sponsor

, , 


Verification Date

October 2021