A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis - Full Text View

Purpose

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

Condition	Intervention	Phase
Alpha-Mannosidosis	Drug: Lamazym Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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.

Resource links provided by NLM:

Genetics Home Reference related topics: alpha-mannosidosis Schindler disease

MedlinePlus related topics: Metabolic Disorders

U.S. FDA Resources

Further study details as provided by Zymenex A/S:

Primary Outcome Measures:

Reduction of oligosaccharides in serum [ Time Frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks ] [ Designated as safety issue: No ]
Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group

Secondary Outcome Measures:

Forced Vital Capacity [ Time Frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks ] [ Designated as safety issue: No ]
Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group
Adverse Events [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
Safety endpoint assessed weekly throughout the trial
Development of clinically significant changes in vital signs and change in physical examination [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
Safety endpoints assessed weekly throughout the trial
Clinical laboratory parameters (hematology, biochemistry and urinalysis) [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
Safety endpoints assessed weekly throughout the trial
Development of Lamazym antibodies and neutralizing/inhibitory antibodies [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
Safety endpoints assessed weekly throughout the trial

Other Outcome Measures:

Quantitative determination of rhLAMAN in plasma [ Time Frame: 10 min, 60 min, 2 hours, 24 hours, 3 days, 7 days ] [ Designated as safety issue: No ]
Pharmacokinetic (PK) assessments. Blood samples are drawn pre-treatment and at various times post-treatment (see time frame above)

Estimated Enrollment:	20
Study Start Date:	August 2012
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Lamazym 1 mg Lamazym/kg body weight	Drug: Lamazym ERT, i.v. infusions weekly Other Names: rhLAMAN recombinant human alpha-mannosidase
Placebo Comparator: Placebo Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol	Drug: Placebo

Eligibility

Ages Eligible for Study:	5 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681953

Locations

Denmark
Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9
Copenhagen, Denmark, DK-2100
France
Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel
Bron, France, 69677
Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter
PARIS Cedex 12, France, 75 571
Germany
Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1
Mainz, Germany, 55131
Poland
The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20
Warszawa, Poland, 04 730
United Kingdom
Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,
Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Zymenex A/S

European Commission

Investigators

Principal Investigator:	Allan M Lund, MD	Copenhagen University Hospital, Center for Metabolic Diseases, Department for Clinical Genetics
Study Chair:	Jens Fogh	Zymenex A/S

More Information

No publications provided

Responsible Party:	Zymenex A/S
ClinicalTrials.gov Identifier:	NCT01681953 History of Changes
Other Study ID Numbers:	rhLAMAN-05, 2012-000979-17
Study First Received:	August 22, 2012
Last Updated:	September 5, 2012
Health Authority:	Denmark: Danish Medicines Agency Germany: Federal Institute for Drugs and Medical Devices United Kingdom: Medicines and Healthcare Products Regulatory Agency France: Agence Nationale de Sécurité du Médicament et des produits de santé Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Additional relevant MeSH terms:

Alpha-Mannosidosis
Mannosidase Deficiency Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors

Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on June 18, 2013