Dose Finding Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis

A Single Center, Randomized, Open-label, Multiple-dose Study of the Efficacy and Long-term Safety of rhLAMAN (Recombinant Human Alpha-mannosidase or Lamazym) for the Treatment of Patients With Alpha-mannosidosis.

This is a single-center, open-label, multiple-dose study of the efficacy and long-term safety of Lamazym for the treatment of patients with alpha-mannosidosis.

Study Overview

• Status: Unknown
• Conditions: Alpha Mannosidosis
• Intervention / Treatment: Drug: Lamazym

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patient must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity in blood leukocytes
2. The patient must have an age at the time of screening ≥ 5 year and ≤ 21 years
3. The patient must have physical ability to perform 6-minutes walk test (6MWT), 3 minute-stair climb test (3MSCT) and pulmonary lung function test (spirometry, body plethysmography).
4. The patient must have the ability to mentally cooperate in the cognitive and motor function tests
5. The patient must have the ability to hear and follow a request. Hearing aids can be worn.
6. Patient or patient's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
7. The patient and his/her guardian(s) must have the ability to comply with the protocol

Exclusion Criteria:

1. The patient cannot walk without support.
2. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
3. History of bone marrow transplantation
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. Presence of an ECHO with abnormalities within half a year that, in the opinion of the Investigator, would preclude participation in the trial
6. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial
7. Pregnancy
8. Psychosis within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lamazym 25; 25 U/kg	Drug: Lamazym; ERT, infusion weekly; Other Names: rhLAMAN
Active Comparator: Lamazym 50; 50 U/kg	Drug: Lamazym; ERT, infusion weekly; Other Names: rhLAMAN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Oligosaccharides in urine	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Oligosaccharides in serum	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months
Reduction of Oligosaccharides in CSF	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months
The distance walked in 6 minutes	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months
The number of steps climbed in 3 minutes	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months
Pulmonary Function	Efficacy endpoint evaluation as change from baseline	3 months (interim evaluation) + 6 months
Adverse events	Safety endpoint assessed weekly throughout the trial	1 week
Development of clinically significant changes in vital signs and change in physical examination	Safety endpoint assessed weekly throughout the trial	1 week
Development of clinically significant changes in the clinical laboratory parameters (hematology, biochemistry and urinalysis)	Safety endpoint assessed every 4th week throughout the trial	4 weeks
Development of rhLAMAN antibodies and neutralizing/inhibitory antibodies	Safety endpoint assessed every other week throughout the trial	2 weeks

Collaborators and Investigators

• Sponsor: Zymenex A/S
• Collaborators: European Commission
• Investigators: Study Chair: Jens Fogh, Zymenex A/S; Principal Investigator: Allan M. Lund, MD, Department of Clinical Genetics, Juliane Marie Centre, Region Hovedstaden, Copenhagen University hospital, Denmark

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Anticipated): November 1, 2012

Study Registration Dates

• First Submitted: January 25, 2011
• First Submitted That Met QC Criteria: January 26, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Estimate): September 26, 2012
• Last Update Submitted That Met QC Criteria: September 25, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mannosidase Deficiency Diseases; alpha-Mannosidosis
• Other Study ID Numbers: rhLAMAN-03; 2010-022085-26 (EudraCT Number)