Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis

Chiesi Farmaceutici S.p.A.

Overview

Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks. Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions

A Screening visit (V1) will take place 7±3 days prior to randomization in order to give the subject enough time to consider their participation in the study, to plan the next visits including the long-stay visits at V2, V5 and V8 (long-stay visits as PK and certain tests are performed over more than one day), and to allow the clinic center to complete the evaluation of the eligibility criteria. Upon confirmation of eligibility, subjects will be randomized to receive weekly i.v. administration of either velmanase alfa 1 mg/kg or placebo. Thereafter, subjects will undergo weekly visits for administration of study treatment and safety data collection. Clinical, laboratory and functional assessments will be performed at the 4-weekly assessment visits with each subject undergoing a minimum of 8 assessment visits (V1 to V8).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Alpha-Mannosidosis

Interventions

Velmanase AlfaDRUG

infusion i.v. treatment

PlaceboDRUG

infusion i.v. treatment

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Confirmed diagnosis of alpha-mannosidosis based on alpha mannosidase activity \<10% of normal in leukocytes or fibroblasts or through genetic testing; * Capability to comply with the protocol; * Evidence of informed consent provided by subject or legally authorized guardian(s) prior to performance of any trial-related activities. Exclusion Criteria: * Previous hematopoietic stem cells transplantation (HSCT) with positive outcome; * Major surgery planned within 3 months prior to study entry or planned during the study that, in the opinion of the Investigator, would preclude participation in the trial; * Known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that would preclude participation in the study in the Investigator's judgment; * Pregnant (as evident by a positive urine hCG or serum-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential \[WOCBP\]) UNLESS they are willing to use highly effective birth control methods; * Participation in other interventional trials testing investigational medicinal products (IMPs) within the last 6 months; * Total IgE \>800 IU/ml; * Any hypersensitivity to velmanase alfa or its excipients that, in the judgment of the Investigator, places the subject at an increased risk for adverse reactions * Clinically active infection and recent vaccinations (within the last month before screening).

Outcomes

Primary Outcomes

Change in concentration of serum oligosaccharides

To evaluate the efficacy of velmanase alfa compared with placebo after 24 weeks of velmanase alfa treatment as measured by Level of serum oligosaccharides;