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

NCT04031066 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: CLI-LMZYMAA2-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Alpha-Mannosidosis

Keywords

Alpha-Mannosidosis; velmanase alfa; alpha-mann; shaman; mannosidosis; alpha-mannosidasis

Outcome Measures

Primary Outcomes (2)

• 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;

  24 weeks (end of study)

• Change in serum level of total immunoglobulin (Ig)G level

  Efficacy of velmanase alfa compared with placebo in alpha mannosidosis subjects based on serum levels of total immunoglobulin (Ig)G after 24 weeks of velmanase alfa treatment

  24 weeks (end of study)

Secondary Outcomes (11)

• Change in Intracellular level of oligosaccharides in peripheral blood leukocytes

  24 weeks (end of study)

• Change in serum IgG Subclasses

  24 weeks (end of study)

• Incidence of Infections

  24 weeks (end of study)

• Assessment of PK parameter Maximum plasma Concentration [Cmax]

  12 weeks

• Assessment of PK parameter Maximum plasma Concentration [Cmax]

  24 weeks (end of study)

Other Outcomes (32)

• Adverse Events (AEs)

  24 weeks (end of study)

• Infusion Related Reactions (IRRs)

  24 weeks (end of study)

• Incidence of Adverse Drug Reactions (ADRs)

  24 weeks (end of study)

Study Arms (2)

Velmanase alfa

EXPERIMENTAL

Drug: Velmanase Alfa

placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Velmanase Alfa DRUG

infusion i.v. treatment

Velmanase alfa

Placebo DRUG

infusion i.v. treatment

placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

MeSH Terms

Conditions

alpha-Mannosidosis; Mannosidase Deficiency Diseases

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paul Harmatz, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized using IRT system
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: double-blind, randomized 2:1 to either velmanase alfa:placebo

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 24, 2019
• Study Start: January 11, 2021
• Primary Completion: October 27, 2021
• Study Completion: December 29, 2021
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share