Avalglucosidase Alfa for Pompe Disease (Baby-COMET Trial)
Recruiting in Palo Alto (17 mi)
+39 other locations
Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Sanofi
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This is a single group, treatment, Phase 3, open-label study to assess efficacy, safety, pharmacokinetic (PK), pharmacodynamics (PD) of avalglucosidase alfa in treatment-naïve male and female participants with IOPD.
Study details include:
* Study duration: Screening - up to 4 weeks;
* Primary Analysis Period (PAP) - 52 weeks;
* Extended Treatment Period (ETP) - 52 weeks;
* Extended Long term Treatment Period (ELTP) - 104 weeks; 4-week follow-up period for a total study duration - up to 4.08 years.
* Treatment duration: Up to 4 years
* Visit frequency: every other week and potentially every week
How is the drug avalglucosidase alfa different from other treatments for Pompe disease?
Avalglucosidase alfa is a second-generation enzyme replacement therapy specifically designed for better uptake by cells and increased clearance of glycogen, which makes it more effective than the current standard treatment, alglucosidase alfa.
23467Is avalglucosidase alfa safe for humans?
Avalglucosidase alfa has been generally well-tolerated in clinical trials for Pompe disease, with most side effects being mild to moderate. Some patients experienced infusion-related reactions, and one patient withdrew due to serious side effects like respiratory distress and chest discomfort.
23467What data supports the effectiveness of the drug avalglucosidase alfa for treating Pompe disease?
Avalglucosidase alfa has shown to be well-tolerated and generally effective in maintaining or improving lung function and physical capacity in patients with late-onset Pompe disease, as seen in a study where most patients completed the treatment without serious side effects. Additionally, it has been designed for better targeting and uptake in the body, potentially leading to improved glycogen clearance compared to the standard treatment.
12345Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.
Eligibility Criteria
This trial is for babies with infantile-onset Pompe disease who haven't been treated before. They must have a confirmed diagnosis, known CRIM status, and cardiomyopathy. Babies can't join if they've been in avalglucosidase alfa trials, have major birth defects unrelated to Pompe disease, other serious diseases, or are on ventilation.Inclusion Criteria
I have been diagnosed with infantile-onset Pompe disease.
I have been diagnosed with cardiomyopathy based on specific heart muscle measurements.
My legal guardian can give consent for me.
Exclusion Criteria
I am experiencing breathing difficulties and may be using a ventilator.
I have received treatment for Pompe disease, like enzyme therapy.
Participant Groups
The study tests the effectiveness and safety of a drug called avalglucosidase alfa in babies with Pompe Disease over up to 4 years. It includes regular visits every week or two for doses and monitoring how well the treatment works and its effects on the body.
1Treatment groups
Experimental Treatment
Group I: Avalglucosidase alfaExperimental Treatment1 Intervention
Administered intravenously every 2 weeks
avalglucosidase alfa is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Nexviazyme for:
- Late-onset Pompe disease
🇪🇺 Approved in European Union as Nexviazyme for:
- Late-onset Pompe disease
🇨🇦 Approved in Canada as Nexviazyme for:
- Late-onset Pompe disease
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Advanced Medical Genetics Site Number : 8400002Hawthorne, NY
Stanford University Site Number : 8400006Stanford, CA
Cincinnati Children's Hospital Medical Center - PIN Site Number : 8400001Cincinnati, OH
Children's Minnesota Site Number : 8400008Minneapolis, MN
More Trial Locations
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Who is running the clinical trial?
SanofiLead Sponsor
Genzyme, a Sanofi CompanyLead Sponsor
References
Biochemical and pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe disease. [2021]Pompe disease results in the accumulation of lysosomal glycogen in multiple tissues due to a deficiency of acid alpha-glucosidase (GAA). Enzyme replacement therapy for Pompe disease was recently approved in Europe, the U.S., Canada, and Japan using a recombinant human GAA (Myozyme, alglucosidase alfa) produced in CHO cells (CHO-GAA). During the development of alglucosidase alfa, we examined the in vitro and in vivo properties of CHO cell-derived rhGAA, an rhGAA purified from the milk of transgenic rabbits, as well as an experimental version of rhGAA containing additional mannose-6-phosphate intended to facilitate muscle targeting. Biochemical analyses identified differences in rhGAA N-termini, glycosylation types and binding properties to several carbohydrate receptors. In a mouse model of Pompe disease, glycogen was more efficiently removed from the heart than from skeletal muscle for all enzymes, and overall, the CHO cell-derived rhGAA reduced glycogen to a greater extent than that observed with the other enzymes. The results of these preclinical studies, combined with biochemical characterization data for the three molecules described within, led to the selection of the CHO-GAA for clinical development and registration as the first approved therapy for Pompe disease.
Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study. [2020]This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) affected 8 patients. Most treatment-emergent AEs/IARs were non-serious with mild-to-moderate intensity. At screening, 5 Switch patients tested positive for anti-avalglucosidase alfa antibodies; on-treatment, 2 Switch and 9 Naïve patients seroconverted. Post-infusion, avalglucosidase alfa plasma concentrations declined monoexponentially (t1/2z∼1.0 h). AUC was 5-6 × higher in the 20 vs 5 mg/kg group. Pharmacokinetics were similar between Switch and Naïve groups and over time. Baseline quadriceps muscle glycogen was low (∼6%) in most patients, generally remaining unchanged thereafter. Exploratory efficacy parameters (pulmonary function/functional capacity) generally remained stable or improved. Avalglucosidase alfa's well-tolerated safety profile and exploratory efficacy results support further avalglucosidase alfa development.
Avalglucosidase alfa: First Approval. [2022]Avalglucosidase alfa (NEXVIAZYME™; avalglucosidase alfa-ngpt) is a hydrolytic lysosomal glycogen-specific recombinant human α-glucosidase product being developed by Sanofi Genzyme (formerly Genzyme Corporation) for the treatment of Pompe disease. Pompe disease is an autosomal recessive lysosomal storage disease caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA), which results in intralysosomal accumulation of glycogen in various tissues. In August 2021, avalglucosidase alfa received its first approval in the USA for the treatment of patients 1 year of age and older with late-onset Pompe disease (GAA deficiency). In July 2021, avalglucosidase alfa received a positive opinion in the EU for long-term enzyme replacement therapy for the treatment of patients with Pompe disease. The drug is under regulatory review in the UK and Japan, and clinical studies are underway in several countries worldwide. This article summarizes the milestones in the development of avalglucosidase alfa leading to this first approval for late-onset Pompe disease.
Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. [2022]Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease.
Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease. [2022]Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed.
Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease. [2022]Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA) and subsequent glycogen accumulation. Avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy designed for increased cellular uptake and glycogen clearance, has been studied for long-term efficacy and safety in patients with late-onset Pompe disease (LOPD). Here we report up to 6.5 years' experience with avalglucosidase alfa during the NEO1 and NEO-EXT studies.
Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial. [2023]In the previously reported Comparative Enzyme Replacement Trial With neoGAA Versus rhGAA (COMET) trial, avalglucosidase alfa treatment for 49 weeks showed clinically meaningful improvements in upright forced vital capacity (FVC) percent predicted and 6-minute walk test (6MWT) compared with alglucosidase alfa.