Clinical Trial: Evaluation of Long-term Efficacy of Treatment With Lamazym

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official 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-Manno

Brief Summary: 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.

Detailed Summary:

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).

Sponsor: Zymenex A/S

Current Primary Outcome:

• 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
• 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

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Drug exposure by Pharmaco Kinetic (PK) sampling profile on plasma [ Time Frame: 1 week ]
  Evaluation of steady state Pharmaco Kinetics
• 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
• Oligosaccharides in urine [ Time Frame: 1 week ]
  Evaluation of steady state

Original Secondary Outcome: Same as current

Information By: Chiesi Farmaceutici S.p.A.

Dates:
Date Received: February 9, 2015
Date Started: February 2015
Date Completion:
Last Updated: March 28, 2017
Last Verified: March 2017