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

Phase 2

• Conditions: Alpha Mannosidosis
• Interventions: Drug: Lamazym

• Registration Number: NCT01285700
• Lead Sponsor: Zymenex A/S

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-25
• Study First Submitted QC: 2011-01-26
• Study First Posted: 2011-01-28
• Primary Completion: 2012-01
• Status Verified: 2012-09
• Last Update Submitted: 2012-09-25
• Last Update Posted: 2012-09-26
• Study Completion: 2012-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lamazym 25	Lamazym	25 U/kg
Lamazym 50	Lamazym	50 U/kg

Primary Outcome Measures

Name	Time	Method
Reduction of Oligosaccharides in urine	3 months (interim evaluation) + 6 months	Efficacy endpoint evaluation as change from baseline

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9; 🇩🇰 Copenhagen, Denmark