Back to resultsA Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis
Primary Purpose
Alpha-Mannosidosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lamazym
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alpha-Mannosidosis
Eligibility Criteria
Inclusion Criteria:
- 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
- The subject must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-Mannosidase activity < 10% of normal activity (historical data)
- The subject must have an age at the time of screening ≥ 5 years and ≤ 35 years
- The subject must have the ability to physically and mentally cooperate in the tests
- The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial
Exclusion Criteria:
- The subjects diagnosis cannot be confirmed by alpha-Mannosidase activity < 10% of normal activity
- The subject cannot walk without support
- Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
- History of BMT
- 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
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
- Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception
- Psychosis; any psychotic disease, also in remission, is an exclusion criteria
- Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
- Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months
- Adult patients who, in the opinion of the Investigator, would be unable to give consent, and who does not have any legal protection or guardianship
- Total IgE >800 IU/ml
- Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol)
Sites / Locations
- Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
- Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel
- Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter
- Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1
- The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20
- Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lamazym
Placebo
Arm Description
1 mg Lamazym/kg body weight
Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol
Outcomes
Primary Outcome Measures
Reduction of oligosaccharides in serum
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
The number of steps climbed in 3 minutes (3-minute stair climb test)
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Secondary Outcome Measures
Forced Vital Capacity
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
The distance walked in 6 minutes (6-minute walk test)
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Adverse Events
Safety endpoint assessed weekly throughout the trial
Development of clinically significant changes in vital signs and change in physical examination
Safety endpoints assessed weekly throughout the trial
Clinical laboratory parameters (hematology, biochemistry and urinalysis)
Safety endpoints assessed weekly throughout the trial
Development of Lamazym antibodies and neutralizing/inhibitory antibodies
Safety endpoints assessed weekly throughout the trial
Full Information
NCT ID
NCT01681953
First Posted
August 22, 2012
Last Updated
July 30, 2020
Sponsor
Zymenex A/S
Collaborators
European Commission
1. Study Identification
Unique Protocol Identification Number
NCT01681953
Brief Title
A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis
Official Title
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zymenex A/S
Collaborators
European Commission
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha-Mannosidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lamazym
Arm Type
Active Comparator
Arm Description
1 mg Lamazym/kg body weight
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol
Intervention Type
Drug
Intervention Name(s)
Lamazym
Other Intervention Name(s)
rhLAMAN, recombinant human alpha-mannosidase
Intervention Description
ERT, i.v. infusions weekly
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Infusions weekly
Primary Outcome Measure Information:
Title
Reduction of oligosaccharides in serum
Description
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Time Frame
Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Title
The number of steps climbed in 3 minutes (3-minute stair climb test)
Description
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Time Frame
Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Secondary Outcome Measure Information:
Title
Forced Vital Capacity
Description
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Time Frame
Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Title
The distance walked in 6 minutes (6-minute walk test)
Description
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Time Frame
Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks
Title
Adverse Events
Description
Safety endpoint assessed weekly throughout the trial
Time Frame
1 week
Title
Development of clinically significant changes in vital signs and change in physical examination
Description
Safety endpoints assessed weekly throughout the trial
Time Frame
1 week
Title
Clinical laboratory parameters (hematology, biochemistry and urinalysis)
Description
Safety endpoints assessed weekly throughout the trial
Time Frame
1 week
Title
Development of Lamazym antibodies and neutralizing/inhibitory antibodies
Description
Safety endpoints assessed weekly throughout the trial
Time Frame
1 week
Other Pre-specified Outcome Measures:
Title
Quantitative determination of rhLAMAN in plasma
Description
Pharmacokinetic (PK) assessments. Blood samples are drawn pre-treatment and at various times post-treatment (see time frame above)
Time Frame
10 min, 60 min, 2 hours, 24 hours, 3 days, 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
The subject must have a confirmed diagnosis of alpha-Mannosidosis as defined by alpha-Mannosidase activity < 10% of normal activity (historical data)
The subject must have an age at the time of screening ≥ 5 years and ≤ 35 years
The subject must have the ability to physically and mentally cooperate in the tests
The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial
Exclusion Criteria:
The subjects diagnosis cannot be confirmed by alpha-Mannosidase activity < 10% of normal activity
The subject cannot walk without support
Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-Mannosidosis
History of BMT
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
Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception
Psychosis; any psychotic disease, also in remission, is an exclusion criteria
Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months
Adult patients who, in the opinion of the Investigator, would be unable to give consent, and who does not have any legal protection or guardianship
Total IgE >800 IU/ml
Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allan M Lund, MD
Organizational Affiliation
Copenhagen University Hospital, Center for Metabolic Diseases, Department for Clinical Genetics
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jens Fogh
Organizational Affiliation
Zymenex A/S
Official's Role
Study Chair
Facility Information:
Facility Name
Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter
City
PARIS Cedex 12
ZIP/Postal Code
75 571
Country
France
Facility Name
Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20
City
Warszawa
ZIP/Postal Code
04 730
Country
Poland
Facility Name
Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26048034
Citation
Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
Results Reference
background
PubMed Identifier
26016802
Citation
Borgwardt L, Thuesen AM, Olsen KJ, Fogh J, Dali CI, Lund AM. Cognitive profile and activities of daily living: 35 patients with alpha-mannosidosis. J Inherit Metab Dis. 2015 Nov;38(6):1119-27. doi: 10.1007/s10545-015-9862-4. Epub 2015 May 28.
Results Reference
background
PubMed Identifier
29716835
Citation
Harmatz P, Cattaneo F, Ardigo D, Geraci S, Hennermann JB, Guffon N, Lund A, Hendriksz CJ, Borgwardt L. Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis. Mol Genet Metab. 2018 Jun;124(2):152-160. doi: 10.1016/j.ymgme.2018.04.003. Epub 2018 Apr 18.
Results Reference
background
PubMed Identifier
29846843
Citation
Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigo D, Cattaneo F, Fogh J, Van den Hout JMH, Beck M, Jones SA, Tylki-Szymanska A, Haugsted U, Lund AM. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018 Nov;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0. Epub 2018 May 30.
Results Reference
result
Links:
URL
https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-000979-17
Description
Study Record on EU Clinical Trials Register including results
Learn more about this trial
A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis
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