A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated with Alglucosidase Alfa

• Register: EUCTR
• Last refreshed on: 4 May 2020
• Main ID: EUCTR2016-003475-21-GB
• Date of registration: 03/01/2017
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated with Alglucosidase Alfa
• Scientific title: An Open-label Ascending Dose Cohort Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of Avalglucosidase Alfa (NeoGAA, GZ402666) in Patients with Infantile-onset Pompe Disease Treated with Alglucosidase Alfa Who Demonstrate Clinical Decline or Sub-optimal Clinical Response
• Date of first enrolment: 17/05/2017
• Target sample size: 34
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003475-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Stage1: ascending dose cohort study design - Stage 2: randomised parallel group study design If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Japan, Taiwan, United Kingdom, United States

Contacts

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V.

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
The patient has confirmed GAA enzyme deficiency from any tissue source.
-The patient who has reached legal age of majority as defined by local regulation, or the patient's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the patient is legally minor per local regulations, assent shall be obtained from
patients, if applicable.
-The patient (and patient’s legal guardian if patient is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol.
-The patient is <18 years old.
-The patient, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not be breastfeeding at screening/baseline.
-The patient has cardiomyopathy at the time of diagnosis: ie, left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations.
-The patient has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry.
-For participants in Stage 1: The patient has documented evidence of clinical decline in at least 1 of the following parameters related to Pompe Disease and NOT related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or cardiac parameters.
- For participants in Stage 2: The patient has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to Pompe Disease and NOT related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or new onset of ptosis.
Are the trial subjects under 18? yes
Number of subjects for this age range: 34
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-The patient has high antibody titer to alglucosidase alfa.
-The patient has a high risk for a severe allergic reaction to Avalglucosidase Alfa (NeoGAA).
-The patient requires any prohibited concomitant medications (e.g., immune modulatory treatment or beta-blockers) for the duration of the study.
-The patient has previously participated in any ACT14132 study cohort.
- Female patient of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Pompe disease (acid alpha-glucosidase deficiency)
MedDRA version: 20.0 Level: LLT Classification code 10036143 Term: Pompe's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.1 Level: PT Classification code 10053185 Term: Glycogen storage disease type II System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Avalglucosidase Alfa (NeoGAA)
Product Code: GZ402666
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Avalglucosidase Alfa (NeoGAA)
CAS Number: 1802558-87-7
Current Sponsor code: GZ402666
Other descriptive name: Recombinant human a-glucosidase conjugated with multiple copies of synthetic bis-mannose-6-phosphate-tetra-mannose glycan Avalglucosidase Alfa (NeoGAA)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: MYOZYME®
Product Name: Myozyme®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ALGLUCOSIDASE ALFA
CAS Number: 420784-05-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: To characterize the pharmacokinetic profile of avalglucosidase alfa and to evaluate the preliminary efficacy of avalglucosidase alfa in comparison to alglucosidase alfa.

Timepoint(s) of evaluation of this end point: Baseline to 25 weeks

Primary end point(s): - Number of participants with adverse events
- Number of participants with immunogenicity response

Main Objective: To evaluate the safety profile of avalglucosidase alfa in patients with infantile-onset Pompe disease (IOPD) previously treated with alglucosidase alfa.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 / to 13 / : Baseline to 25 weeks
14 / and 15 / : Up to 7 years

Secondary end point(s): 1 / Assessment of pharmacokinetic parameter: maximum plasma concentration (Cmax)
Assessment of pharmacokinetic parameter: time to achieve maximum plasma concentration (tmax)
2 / Assessment of pharmacokinetic parameter: area under curve (AUC0 to last)
Assessment of pharmacokinetic parameter: terminal half-life (t1/2z)
3 / Change from baseline in Gross Motor Function Measure-88 Test
4 / Change from revised Gross Motor Function Classification System score
5 / Change from baseline in Pompe specific Pediatric Evaluation of Disability Inventory (Pompe PEDI), Functional Skills Scale: Mobility Domain Test score (normative standard score)
6 / Change from baseline for Pompe PEDI Functional Skills Scale: Mobility Domain Test score (scaled score)
7 / Change from baseline in Quick Motor Function Test scores
8 / Change from baseline in Left Ventricular Mass Index
9 / Change from baseline in Left Ventricular Mass Index Z score
10 / Change from baseline in Eyelid position measurements
Interpalpebral fissure distance (IPFD)
11 / Change from baseline in Eyelid position measurements: Margin reflex distance-1 (MRD-1)
12 / Change from baseline in Eyelid position measurements: Margin pupil distance (MPD)
13/ Change from baseline in Creatine kinase value
14 / Number of participants with adverse events
15 / Number of participants with immunogenicity response

Secondary ID(s)

ACT14132

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date: 17/05/2017
Contact: