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

Phase 3
Completed
Conditions
Alpha-Mannosidosis
Interventions
Drug: Placebo
Registration Number
NCT01681953
Lead Sponsor
Zymenex A/S
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LamazymLamazym1 mg Lamazym/kg body weight
PlaceboPlaceboPlacebo is formulated as an isotonic phosphate buffer with glycine and mannitol
Primary Outcome Measures
NameTimeMethod
The number of steps climbed in 3 minutes (3-minute stair climb test)Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group

Reduction of oligosaccharides in serumBaseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

Primary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group

Secondary Outcome Measures
NameTimeMethod
Development of clinically significant changes in vital signs and change in physical examination1 week

Safety endpoints assessed weekly throughout the trial

Clinical laboratory parameters (hematology, biochemistry and urinalysis)1 week

Safety endpoints assessed weekly throughout the trial

Forced Vital CapacityBaseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

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)Baseline evaluation prior to first dose, midterm evaluation after 26 weeks, and end evaluation after 52 weeks

Secondary efficacy endpoint evaluated as change from baseline in the active group versus the placebo group

Development of Lamazym antibodies and neutralizing/inhibitory antibodies1 week

Safety endpoints assessed weekly throughout the trial

Adverse Events1 week

Safety endpoint assessed weekly throughout the trial

Trial Locations

Locations (6)

Center for Metabolic Diseases, Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9

🇩🇰

Copenhagen, Denmark

Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Langenbeckstrasse 1

🇩🇪

Mainz, Germany

Hôpital Femme Mère Enfant, Lyon, 59 boulevard Pinel

🇫🇷

Bron, France

The Children's Memorial Health Institute Warsaw, Department of Metabolic Diseases, Al Dzieci Polskich 20

🇵🇱

Warszawa, Poland

Genetic Medicine, 6th floor, St Mary's Hospital, Oxford Road,

🇬🇧

Manchester, United Kingdom

Hôpital Trousseau, Service de neuropédiatrie, Centre Référence des Maladies Lysosomales, 26 avenue du Docteur Arnold Netter

🇫🇷

PARIS Cedex 12, France

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