A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis

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

Sponsors

Lead sponsor: Chiesi Farmaceutici S.p.A.

Source Chiesi Farmaceutici S.p.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

Detailed Description

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).

Overall Status Not yet recruiting
Start Date April 8, 2020
Completion Date March 29, 2021
Primary Completion Date March 15, 2021
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in concentration of serum oligosaccharides 24 weeks (end of study)
Change in serum level of total immunoglobulin (Ig)G level 24 weeks (end of study)
Secondary Outcome
Measure Time Frame
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)
Assessment of PK parameter Area Under the Curve [AUC] 24 weeks (end of study)
Assessment of PK parameter Area Under the Curve [AUC] 12 weeks
Assessment of PK parameter Elimination half-life [t1/2] 12 weeks
Assessment of PK parameter Elimination half-life [t1/2] 24 weeks (end of study)
Assessment of PK parameter trough concentration (Ctrough) 12 weeks
Assessment of PK parameter trough concentration (Ctrough) 24 weeks (end of study)
Enrollment 12
Condition
Intervention

Intervention type: Drug

Intervention name: Velmanase Alfa

Description: infusion i.v. treatment

Arm group label: Velmanase alfa

Intervention type: Drug

Intervention name: Placebo

Description: infusion i.v. treatment

Arm group label: placebo

Eligibility

Criteria:

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).

Gender: All

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Paul Harmatz, MD Principal Investigator UCSF Benioff Children’s Hospital Oakland
Overall Contact

Last name: Chiesi Clinical Trial Info

Phone: +3905212791

Email: [email protected]

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Velmanase alfa

Arm group type: Experimental

Arm group label: placebo

Arm group type: Placebo Comparator

Acronym SHAMAN
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: double-blind, randomized 2:1 to either velmanase alfa:placebo

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking description: Randomized using IRT system

Source: ClinicalTrials.gov