A Placebo-Controlled phase 3 trial of repeated Lamazym treatment of subjects with Alpha-Mannosidosis

• Register: EUCTR
• Last refreshed on: 23 November 2015
• Main ID: EUCTR2012-000979-17-DE
• Date of registration: 09/07/2012
• Prospective Registration: Yes
• Primary sponsor: Zymenex A/S
• Public title: A Placebo-Controlled phase 3 trial of repeated Lamazym treatment of subjects with Alpha-Mannosidosis
• Scientific 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 - Phase III
• Date of first enrolment: 17/12/2012
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000979-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Denmark, Germany, Spain, Sweden

Contacts

• Name: CEO
• Affiliation: Zymenex A/S

• Name: CEO
• Affiliation: Zymenex A/S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities
2. The subject and his/her guardian(s) must have the ability to comply with the protocol
3. The subject must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity (historical data)
4. The subject must have an age at the time of screening = 5 years and = 35 years
5. The subject must have the ability to physically and mentally cooperate in the tests
6. The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. The subjects diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity
2. The subject cannot walk without support
3. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis
4. History of BMT
5. 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
6. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
7. Pregnancy: Pregnant woman are 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
8. Psychosis; any psychotic disease, also in remission, is an exclusion criteria
9. Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial
10. Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months
11. 11. 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
12. Total IgE >800IU/ml
13. 13. Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatement of Alpha-Mannosidosis

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Lamazym
Product Code: rhLAMAN
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: rhLAMAN
Current Sponsor code: rhLAMAN
Other descriptive name: recombinant human alpha-mannosidase
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoints is change from baseline in the active treated group versus the placebo group:
• The level of oligosaccharides in serum
• 3-minute stair climb test (3MSCT)

Secondary Objective: PK evaluation

Timepoint(s) of evaluation of this end point: Efficacy will be assessed at the Danish site at baseline (prior to first dose), as midterm evaluation (after 26±3 weeks, referred to as midterm evaluation or visit 26a), and as end evaluation (after 52±3 weeks, referred to as end evaluation or visit 52a).

Main Objective: 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

Secondary Outcome(s)

Secondary end point(s): Prioritized Secondary Efficacy Endpoints:
• Forced Vital Capacity (FVC)
• 6 minute walk test (6MWT)

Other Secondary Efficacy Endpoints:
• Bruininks-Oseretsky test of Motor Proficiency (BOT2)
• Leiter R
• Cerebrospinal fluid biomarkers incl oligosaccharide and standard tests
• Pulmonary Function Tests
• Pure tone audiometry (PTA)
• Questionnaires (CHAQ and EQ-5D)

Safety Endpoints:
• Adverse events (AEs)
• Vital signs and change in physical examination
• Clinical laboratory parameters (hematology, biochemistry and urinalysis)
• Development of Lamazym antibodies and neutralizing/inhibitory antibodies

Pharmacokinetic endpoints:
• Pharmacokinetics (PK)

Timepoint(s) of evaluation of this end point: Efficacy will be assessed at the Danish site at baseline (prior to first dose), as midterm evaluation (after 26±23 weeks, referred to as midterm evaluation or visit 26a), and as end evaluation (after 52±3 weeks, referred to as end evaluation or visit 52a).
Safety will be assessed at every visit.
PK will be analyzed at visit 1.

Secondary ID(s)

2012-000979-17

rhLAMAN-05

Source(s) of Monetary Support

EU FP7 ALPHA-MAN