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

• 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

• 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

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

• Drug: Lamazym
  ERT, i.v. infusions weekly
  Other Names:

  • rhLAMAN
  • recombinant human alpha-mannosidase
• Drug: Placebo

• Active Comparator: Lamazym
  1 mg Lamazym/kg body weight
  Intervention: Drug: Lamazym
• Placebo Comparator: Placebo
  Placebo is formulated as an isotonic phosphate buffer with glycine and mannitol
  Intervention: Drug: Placebo

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)