avalglucosidase alfa GZ402666 for Glycogen Storage Disease Type II;Pompe's Disease

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Investigational Site Number 8400001, Durham, NC
Glycogen Storage Disease Type II;Pompe's Disease+2 More
avalglucosidase alfa GZ402666 - Drug
Eligibility
< 18
All Sexes
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Study Summary

This study is evaluating whether a new drug called alglucosidase alfa is safe for people with Pompe disease.

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Eligible Conditions

  • Glycogen Storage Disease Type II;Pompe's Disease

Treatment Effectiveness

Effectiveness Progress

1 of 3

Other trials for Glycogen Storage Disease Type II;Pompe's Disease

Study Objectives

This trial is evaluating whether avalglucosidase alfa GZ402666 will improve 2 primary outcomes and 35 secondary outcomes in patients with Glycogen Storage Disease Type II;Pompe's Disease. Measurement will happen over the course of From Baseline to Week 25.

Baseline to 25 weeks
Assessment of pharmacokinetic parameter: area under curve (AUC0-last)
Assessment of pharmacokinetic parameter: maximum plasma concentration (Cmax)
Assessment of pharmacokinetic parameter: terminal half-life (t1/2z)
Assessment of pharmacokinetic parameter: time to achieve maximum plasma concentration (tmax)
Change from baseline in Creatine kinase value
Change from baseline in Eyelid position measurements: Interpalpebral fissure distance (IPFD)
Change from baseline in Eyelid position measurements: Margin pupil distance (MPD)
Change from baseline in Eyelid position measurements: Margin reflex distance-1 (MRD-1)
Change from baseline in Gross Motor Function Measure-88 Test
Change from baseline in Left Ventricular Mass Index
Change from baseline in Left Ventricular Mass Index Z score
Change from baseline in Pompe PEDI Functional Skills Scale: Mobility Domain Test score (scaled score)
Change from baseline in Pompe specific Pediatric Evaluation of Disability Inventory (Pompe PEDI) Functional Skills Scale: Mobility Domain Test score (normative standard score)
Change from baseline in Quick Motor Function Test scores
Change from revised Gross Motor Function Classification System score
Baseline, Week 25
PAP: Change From Baseline in Creatine Kinase Value at Week 25
PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25
PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25
PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25
PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25
PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25
PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25
PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25
PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25
Week 25
PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa
PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa
PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa
Week 25
PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa
PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa
Week 25
PAP: Number of Participants With Anti-drug Antibody (ADA) Response
PAP: Number of Participants With Infusion-associated Reactions (IARs)
PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI)
Week 371
ETP: Number of Participants With Infusion-associated Reactions
ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest
Up to 7 years
Number of participants with adverse events
Number of participants with immunogenicity response

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Other trials for Glycogen Storage Disease Type II;Pompe's Disease

Trial Design

6 Treatment Groups

alglucosidase alfa
1 of 6
avalglucosidase alfa
1 of 6
Cohort 1: Avalglucosidase Alfa 20 mg/kg
1 of 6
Cohort 3b: Alglucosidase Alfa in PAP
1 of 6
Cohort 2: Avalglucosidase Alfa 40 mg/kg
1 of 6
Cohort 3a: Avalglucosidase Alfa 40 mg//kg
1 of 6
Active Control
Experimental Treatment

This trial requires 22 total participants across 6 different treatment groups

This trial involves 6 different treatments. Avalglucosidase Alfa GZ402666 is the primary treatment being studied. Participants will be divided into 5 treatment groups. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.

avalglucosidase alfa
Drug
Administered intravenously every 2 weeks as an ascending dose cohort
Cohort 1: Avalglucosidase Alfa 20 mg/kg
Drug
Avalglucosidase alfa, 20 mg/kg intravenous (IV) infusion every other week (qow) for 25 weeks in the Primary Analysis Period (PAP), followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP).
Cohort 3b: Alglucosidase Alfa in PAPAfter determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose [between 20 mg/kg qow and 40 mg/kg weekly as per physician] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP.
Cohort 2: Avalglucosidase Alfa 40 mg/kg
Drug
Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
Cohort 3a: Avalglucosidase Alfa 40 mg//kg
Drug
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
alglucosidase alfa
Drug
administered intravenously at current stable dose (i.e. administered regularly for a minimum of 6 months immediately prior to study entry)

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to 7 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly up to 7 years for reporting.

Closest Location

Investigational Site Number 8400001 - Durham, NC

Eligibility Criteria

This trial is for patients born any sex aged 18 and younger. There are 9 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
The participants has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source.
The participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable.
The participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol.
The participants is less than 18 years old.
The participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/Baseline.
The participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations.
The participant 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 participant 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 participant 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.

Patient Q&A Section

What is acid maltase deficiency?

"Acid maltase deficiency should be suspected in patients with the following clinical presentation: failure to thrive, lactic acidosis, failure to thrive without acid maltase deficiency, failure to thrive with lactic acidosis and/or acid maltase deficiency, or neonatal presentation with acid maltase deficiency. A deficiency of acid maltase can cause severe brain and/or liver damage, and even death." - Anonymous Online Contributor

Unverified Answer

Can acid maltase deficiency be cured?

"We conclude that AAD is a monogenic disorder and hence, curable. Patients with this disorder in whom AAD is the probable diagnosis, although the clinical phenotype often appears to be mild or atypical, may not realize the seriousness of the disorder so should be assessed for AAD." - Anonymous Online Contributor

Unverified Answer

What are common treatments for acid maltase deficiency?

"The disorder is characterized by hyperammonemia resulting from deficient enzymatic degradation of the intestinal brush border membrane-bound enzyme maltase. Hyperammonemia is treated with oral valproic acid. Although symptomatic valproic acid therapy is widely used for acid maltase deficiency, anecdotal reports exist of the use of parenteral valproic acid for this condition." - Anonymous Online Contributor

Unverified Answer

What causes acid maltase deficiency?

"The precise cause of the disorder is now recognized to be most frequently caused by the loss of the acidic α-amylase enzyme and is only a small part of the complex mechanism of this disease. We recommend that the disorder be included in the clinical and laboratory definition of the group of malabsorption disorders. summary: This article discusses acid maltase deficiency. A more general discussion of this disorder can be found on the Disorders of Lipid Metabolism website." - Anonymous Online Contributor

Unverified Answer

What are the signs of acid maltase deficiency?

"Symptoms in a patient with AAD can generally be divided into one of three groups; digestive, neuromuscular, or other signs. The severity of the symptoms vary depending on the severity of the deficiency.\n" - Anonymous Online Contributor

Unverified Answer

How many people get acid maltase deficiency a year in the United States?

"There are about 100,000 people in the United States who suffer ACD, with 10 to 90% being children. There is a need to better diagnose this disease and to educate the public that ACD constitutes a public health problem." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets acid maltase deficiency?

"At one moment in time, some individuals are affected by the disorder and those who are affected may not be aware they are affected by this disease. However, the average age of individuals can be ascertained by combining current prevalence of the condition with the age of the first diagnosis of the condition. For the average age of diagnosis of acid maltase deficiency to be determined, one needs to use two separate sources. These sources are the reported first date of diagnosis of the disease and the prevalence of the disorder. The age at which a person is first diagnosed with the disorder has an expected value because it is possible for multiple individuals to be diagnosed with the disorder at different times, it is also possible for a number of family members to have the disorder." - Anonymous Online Contributor

Unverified Answer

Does avalglucosidase alfa gz402666 improve quality of life for those with acid maltase deficiency?

"For patients with a GLA mutation in the HEXA gene, treatment with gz402666 has significantly improved overall quality of life and was well-tolerated. In addition, treatment with gz402666 has been found to be particularly beneficial for improvement in upper respiratory symptoms for HEXA-mutation carriers." - Anonymous Online Contributor

Unverified Answer

What are the common side effects of avalglucosidase alfa gz402666?

"There have been no significant side effects reported following the initiation of treatment with AGL or its combination with a gluten-free diet. Data from a recent study have led to the conclusion that AGL and gluten-free diet are safe and effective treatments which may facilitate the normalization of clinical, biological, and histological features of GAI." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating acid maltase deficiency?

"The following are current and new treatments, along with their mechanism of action, efficacy, and adverse events:\n\n- Oral alginate\n- Intradermal injections of somatostatin\n- Intradermal injections of calcitonin/eelcalcitonin\n- Intradermal injections of somatostatin receptor agonists\nIt may be hard to find a treatment that has a cure in the short term for people with AMD. Treatment is generally long-term, and many people have been diagnosed only in adulthood." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving avalglucosidase alfa gz402666?

"No clinical trials involving avalglucosidase alfa for Pompe disease have been reported in the literature up to February 2010. Our search for Pompe disease gene treatment trials on ClinicalTrials.gov for the past 36 months will continue for the foreseeable future and was limited by publication date. The search will additionally search for placebo-controlled, randomized trials on which some Pompe disease experts are experts." - Anonymous Online Contributor

Unverified Answer

Is avalglucosidase alfa gz402666 safe for people?

"Results from a recent paper showed gz402666 to be safe, well tolerated and acceptable for people with NIP and MPS type I. This is the first large-scale, placebo-controlled, randomised, double-blind, placebo-controlled trial of gz402666 in patients with MPS I. Results from a recent paper demonstrate the ability of gz402666 to slow disease progression." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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