Clinical trial NCT04031066: Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Alpha-Mannosidosis
Keywords: Alpha-Mannosidosis
velmanase alfa
alpha-mann
shaman
mannosidosis
alpha-mannosidasis
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2019-07-24
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind, randomized 2:1 to either velmanase alfa:placebo
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Change in concentration of serum oligosaccharides
timeFrame: 24 weeks (end of study)
measure: Change in serum level of total immunoglobulin (Ig)G level
timeFrame: 24 weeks (end of study)
Secondary outcomes:
measure: Change in Intracellular level of oligosaccharides in peripheral blood leukocytes
timeFrame: 24 weeks (end of study)
measure: Change in serum IgG Subclasses
timeFrame: 24 weeks (end of study)
measure: Incidence of Infections
timeFrame: 24 weeks (end of study)
measure: Assessment of PK parameter Maximum plasma Concentration [Cmax]
timeFrame: 12 weeks
measure: Assessment of PK parameter Maximum plasma Concentration [Cmax]
timeFrame: 24 weeks (end of study)
measure: Assessment of PK parameter Area Under the Curve [AUC]
timeFrame: 24 weeks (end of study)
measure: Assessment of PK parameter Area Under the Curve [AUC]
timeFrame: 12 weeks
measure: Assessment of PK parameter Elimination half-life [t1/2]
timeFrame: 12 weeks
measure: Assessment of PK parameter Elimination half-life [t1/2]
timeFrame: 24 weeks (end of study)
measure: Assessment of PK parameter trough concentration (Ctrough)
timeFrame: 12 weeks
measure: Assessment of PK parameter trough concentration (Ctrough)
timeFrame: 24 weeks (end of study)
Other outcomes:
measure: Adverse Events (AEs)
timeFrame: 24 weeks (end of study)
measure: Infusion Related Reactions (IRRs)
timeFrame: 24 weeks (end of study)
measure: Incidence of Adverse Drug Reactions (ADRs)
timeFrame: 24 weeks (end of study)
measure: Anty-Drug Antibody (ADA) level
timeFrame: 24 weeks (end of study)
measure: Neutralizing Antibody (NAb) level
timeFrame: 24 weeks (end of study)
measure: Change on Immunoglobuline Type A (IgA) values
timeFrame: 24 weeks (end of study)
measure: Change on Immunoglobuline Type M (IgM) values
timeFrame: 24 weeks (end of study)
measure: Change on B-cell immunophenotype level
timeFrame: 24 weeks (end of study)
measure: 3MSCT (3-Minute Stair Climb Test)
timeFrame: 24 weeks (end of study)
measure: 6MWT (2MWT for children) (6- or 2-Minute Walk Test)
timeFrame: 24 weeks (end of study)
measure: FVC, FEV1 and PEF
timeFrame: 24 weeks (end of study)
measure: Psychotic events
timeFrame: 24 weeks (end of study)
measure: Shoulder mobility
timeFrame: 24 weeks (end of study)
measure: ECG PR interval
timeFrame: 24 weeks (end of study)
measure: ECG QT interval
timeFrame: 24 weeks (end of study)
measure: ECG QRS duration
timeFrame: 24 weeks (end of study)
measure: Heart diseases
timeFrame: 24 weeks (end of study)
measure: Hearing testing
timeFrame: 24 weeks (end of study)
measure: Kaufman-II (Kaurfman Assessment Battery for Children - 2nd Edition)
timeFrame: 24 weeks (end of study)
measure: Bayley-III (Bayley Scales of Infant and Toddler Development - 3rd Edition)
timeFrame: 24 weeks (end of study)
measure: VABS-3 scores (Vineland Adaptive Behavior Scales - 3rd Edition)
timeFrame: 24 weeks (end of study)
measure: Development Motor scale
timeFrame: 24 weeks (end of study)
measure: EQ-5D-5L (European Quality of Life Five Dimension Five Level) Questionnaire
timeFrame: 24 weeks (end of study)
measure: CHAQ (Childhood Health Assessment Questionnaire)
timeFrame: 24 weeks (end of study)
measure: MPS Health Assessment Questionnaire
timeFrame: 24 weeks (end of study)
measure: Zarit Burden Interview
timeFrame: 24 weeks (end of study)
measure: CBCL (Child Behavioral Checklist) or ABCL (Adult Behavioral Checklist) according to age
timeFrame: 24 weeks (end of study)
measure: PEDI (Pediatric Evaluation of Disability Inventory)
timeFrame: 24 weeks (end of study)
measure: PROMIS-SF (Patient-reported Outcomes Measurement Information System Short Forms)
timeFrame: 24 weeks (end of study)
measure: Service-use and cost questionnaire to patient and families
timeFrame: 24 weeks (end of study)
measure: Physician's Judgement of Overall Response
timeFrame: 24 weeks (end of study)
measure: Caregiver's Judgement of Overall Response
timeFrame: 24 weeks (end of study)
Locations:
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Paul Harmatz, MD
role: PRINCIPAL_INVESTIGATOR
References: