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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Zymenex A/S
ClinicalTrials.gov Identifier:
NCT01681953
First received: August 22, 2012
Last updated: September 5, 2012
Last verified: September 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 31, 2014