alpha-Mannosidosis MedDRA version: 17.1 Level: LLT Classification code 10032658 Term: Other specified disorders of carbohydrate transport and metabolism System Organ Class: 100000004850
Conditions
Interventions
Product Name: Lamazym
Product Code: rhLAMAN
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: recombinant human lysosomal alpha-mannosidase
Other descriptive name: LAMAZYM
Con
Sponsors
Zymenex A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject must have participated in the phase 1 trial (EudraCT number: 2010-022084-36), phase 2a trial (EudraCT number: 2010-022085-26), phase 2b trial (EudraCT number: 2011-004355-40) or phase 3 trial (EudraCT number: 2012-000979-17) 2. The subject must still be receiving weekly intravenous infusions of Lamazym according to the AfterCare Program 3. The Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities 4. The subject and his/her guardian(s) must have the ability to comply with the protocol Are the trial subjects under 18? yes Number of subjects for this age range: 7 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of bone marrow transplantation 2. 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. Subjects unable to perform the motor tests independently from support are permitted to participate in the trial and will be evaluated for the remnant non motor endpoints 3. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator, would preclude participation in the trial 4. Pregnant and/or lactating women cannot participate in the trial. Concerning women of child bearing potential (WOCBP), the investigators will decide whether or not there is a need for contraception. This assessment will be done through interviews with the patient and parents. 5. Participation in other interventional trials testing IMP, including rhLAMAN-07 (EudraCT number: 2013-000336-97) and rhLAMAN-09 (EudraCT number: 2013-000321-31) trials with Lamazym 6. Pause of the IMP for 2 consecutive weeks during the last month. Subjects are allowed to be re-screened
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall objective is to evaluate the long-term efficacy of Lamazym i.v. treatment in patients with alpha-Mannosidosis previously enrolled in Lamazym trials and currently receiving the treatment according to the AfterCare Program. The primary objective of the trial is to evaluate the impact of the long-term treatment with Lamazym upon the level of biomarker oligosaccharides in serum and upon the endurance as measured by the change from baseline in the number of steps climbed in 3 minutes (3MSCT). ;Secondary Objective: As secondary objectives, the long term efficacy of Lamazym will be investigated upon endurance as measured by the change from baseline in the number of meters walked in six minutes (6MWT), upon pulmonary function, motor proficiency by BOT-2 and hearing capability by audiometry. In addition, cognitive development will be assessed by Leiter-R test. CNS involvement will be evaluated with MRI/MRS (for patients who previously participated in rhLAMAN-02 trial), CSF biomarkers (Tau, NFL, GFAp) and CSF biomarkers oligosaccharides. Clearance of oligosaccharides in urine will be measured.;Primary end point(s): • Oligosaccharides in serum • 3 Minute Stair Climb Test (3MSCT) ;Timepoint(s) of evaluation of this end point: Endpoints assessed at one evaluation visit only. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical parameters: • 6 Minute Walk Test (6MWT) • Pulmonary function (FVC, FEV1, PEF) • Functional capacity according to Bruininks-Oseretsky test of Motor Proficiency (BOT-2) • Pure Tone Audiometry (PTA) Cognitive ability: • Equivalence age measured by Leiter R CNS parameters: • Assessment of mannose-rich oligosaccharides in brain tissue as measured by MRS visual score (for patients who previously participated in rhLAMAN-02), MRI diffusion coefficient in white matter, gray matter and centrum semi oval • Cerebrospinal fluid neuro-degeneration biomarkers (Tau, NFL, GFAp) • Oligosaccharides in CSF Additional laboratory: • Drug exposure by PK sampling profile on plasma • Oligosaccharides in urine • Measurement of in vivo biological activity Quality of life based on questionnaires filled by the subject’s guardian, will be evaluated by: • CHAQ • EQ-5D-5L Safety Endpoints: • Development of adverse events • Development of clinically significant changes in vital signs and change in physical examination • Development of clinically significant changes in the clinical laboratory parameters (hematology, biochemistry and urinalysis) • Development of rhLAMAN antibodies and neutralizing/inhibitory antibodies.;Timepoint(s) of evaluation of this end point: Endpoints assessed at one evaluation visit only. | — |
Countries
Denmark
Contacts
Public ContactCEO
Zymenex A/S
Outcome results
None listed