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Completed

NCT Number: NCT02478840

Evaluation of Long-term Efficacy of Treatment With Lamazym

The overall objective is to evaluate the long-term efficacy of Lamazym i.v. treatment in patients with alpha-Mannosidosis previously enrolled in Lamazym trials and currently receiving the treatment according to the AfterCare Program.

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Key information

Conditions

Alpha-Mannosidosis Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Lysosomal Storage Diseases Mannosidase Deficiency Diseases Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9

Copenhagen, DK-2100, Denmark

About this study

The primary objective of the trial is to evaluate the impact of the long-term treatment with Lamazym upon the level of biomarker oligosaccharides in serum and upon the endurance as measured by the change from baseline in the number of steps climbed in 3 minutes (3MSCT).

As secondary objectives, the long term efficacy of Lamazym will be investigated upon endurance as measured by the change from baseline in the number of meters walked in six minutes (6MWT), upon pulmonary function, motor proficiency by BOT-2 and hearing capability by audiometry. In addition, cognitive development will be assessed by Leiter-R test. CNS involvement will be evaluated with MRI/MRS (for patients who previously participated in rhLAMAN-02 trial), CSF biomarkers (Tau, NFL, GFAp) and CSF biomarkers oligosaccharides. Clearance of oligosaccharides in urine will be measured.

Long-term safety and Pharmaco-Kinetic (PK) profile after long-term treatment as measured by rhLAMAN levels in plasma will be assessed as well.

Quality of life will be assessed by questionnaires (CHAQ and EQ-5D-5L).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • The subject must have participated in the phase 1 trial (EudraCT number: 2010-022084-36), phase 2a trial (EudraCT number: 2010-022085-26), phase 2b trial (EudraCT number: 2011-004355-40) or phase 3 trial (EudraCT number: 2012-000979-17)
  • The subject must still be receiving weekly intravenous infusions of Lamazym according to the AfterCare Program
  • The Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities
  • The subject and his/her guardian(s) must have the ability to comply with the protocol

Exclusion criteria

  • History of bone marrow transplantation
  • 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. Subjects unable to perform the motor tests independently from support are permitted to participate in the trial and will be evaluated for the remnant non motor endpoints
  • Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial
  • Pregnant and/or lactating women cannot participate in the trial. Concerning women of child bearing potential (WOCBP), the investigators will decide whether or not there is a need for contraception. This assessment will be done through interviews with the patient and parents.
  • Participation in other interventional trials testing IMP, including rhLAMAN-07 (EudraCT number: 2013-000336-97) and rhLAMAN-09 (EudraCT number: 2013-000321-31) trials with Lamazym
  • Pause of the IMP for 2 consecutive weeks during the last month. Subjects are allowed to be re-screened

Treatment and study plan

Lamazym

Drug

recombinant human alpha-mannosidase

Other names: rhLAMAN

Primary outcomes

  1. Change from baseline in reduction of oligosaccharides in serum

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Primary Endpoint evaluation as change

  2. Change from baseline in 3 Minutes Stair Climb Test (3MSCT)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Primary Endpoint evaluation as change

Secondary outcomes

  1. 6 Minute Walk Test (6MWT)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  2. Pulmonary function: Forced Vital Capacity (FVC)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  3. Pulmonary function: Forced Expiratory Volume during first second (FEV1)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  4. Pulmonary function: Peak Expiratory Flow Rate (PEF)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  5. Functional capacity according to Bruininks-Oseretsky test of Motor Proficiency (BOT-2)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  6. Pure Tone Audiometry (PTA)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  7. Equivalence age measured by Leiter International Performance Scale-Revised (Leiter-R)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  8. Assessment of mannose-rich oligosaccharides in brain tissue as measured by Magnetic Resonance Spectroscopy (MRS) visual score (for patients who previously participated in rhLAMAN-02)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  9. Assessment of mannose-rich oligosaccharides in brain tissue as measured by Magnetic Resonance Imaging (MRI) diffusion coefficient (for patients who previously participated in rhLAMAN-02)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  10. Cerebrospinal fluid biomarkers: Oligosaccharides in Cerebrospinal Fluid (CSF)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  11. Cerebrospinal fluid neuro-degeneration biomarkers: Tau Protein (Tau) in Cerebrospinal Fluid (CSF)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  12. Cerebrospinal fluid neuro-degeneration biomarkers: Neurofilament Protein Light (NFL) in Cerebrospinal Fluid (CSF)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  13. Cerebrospinal fluid neuro-degeneration biomarkers: Glial Fibrillary Acidic protein (GFAp) in Cerebrospinal Fluid (CSF)

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    Endpoint evaluation as change

  14. Drug exposure by Pharmaco Kinetic (PK) sampling profile on plasma

    Time frame: 1 week

    Evaluation of steady state Pharmaco Kinetics

  15. Measurement of in vivo biological activity of Lamazym in blood before and after Infusion of Lamazym

    Time frame: 1 week

    Comparing with Anti Body (AB) and PK measurements. Measuring unit is mU/mL

  16. Oligosaccharides in urine

    Time frame: 1 week

    Evaluation of steady state

Other outcomes

  1. Quality of life based on questionnaires

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    filled by the subject's guardian, will be evaluated by Childhood Health Assessment Questionnaire (CHAQ) questionnaires filled in by the subject's guardian, will be evaluated by CHAQ and EQ-5D-5L

  2. Quality of life based on questionnaires

    Time frame: Baseline evaluation prior to first dose compared to evaluation after one, two or four years of treatment

    filled by the subject's guardian, will be evaluated by Health Questionnaire (EQ-5D-5L) questionnaires filled in by the subject's guardian, will be evaluated by CHAQ and EQ-5D-5L

  3. Development of adverse events

    Time frame: 1 week

    Safety endpoint assessed from signing of the Informed Consent Form (ICF)

  4. Development of clinically significant changes in vital signs and change in physical examination

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

  5. Development of clinically significant changes in the clinical laboratory Parameters: Hematology

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

  6. Development of clinically significant changes in the clinical laboratory Parameters: Biochemistry

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

  7. Development of clinically significant changes in the clinical laboratory Parameters: Urinalysis

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

  8. Development of rhLAMAN antibodies

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

  9. Development of rhLAMAN neutralizing/inhibitory antibodies

    Time frame: 1 week

    Safety endpoint assessed throughout the trial

Sponsors and collaborators

Lead sponsor

Zymenex A/S

Industry

Registry information

Official study title

A Single Center, Open Label Clinical Trial Investigating the Long-term Efficacy of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) Treatment in Subjects With Alpha-Mannosidosis Who Previously Participated in Lamazym Trials

Acronym: rhLAMAN-10

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Jun 23, 2015
Registry last updated
Nov 20, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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