Avalglucosidase Alfa for Pompe Disease

(Baby-COMET Trial)

Recruiting at 42 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Disqualifiers: Respiratory insufficiency, Congenital abnormality, Organic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

17 Participants Needed

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

Will 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.

Will 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.

What 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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug avalglucosidase alfa for Pompe disease?

Avalglucosidase alfa has shown clinically meaningful improvements in lung function and walking ability in patients with late-onset Pompe disease, as demonstrated in a 97-week clinical trial. Additionally, it was well-tolerated and generally maintained or improved pulmonary function and functional capacity in a phase 1 study. ^{1 2 3 5 6}

Is 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. ^{1 2 5 6 7}

Is 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, but no life-threatening events or deaths were reported. ^{1 2 5 6 7}

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. ^{1 2 5 6 7}

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, making it more effective than the current standard treatment, alglucosidase alfa, for late-onset Pompe disease. ^{1 2 5 6 7}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

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.

Participants with major congenital abnormality

You have participated in a clinical trial for avalglucosidase alfa before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Primary Analysis Period (PAP)

Participants receive avalglucosidase alfa intravenously to assess efficacy, safety, pharmacokinetics, and pharmacodynamics

52 weeks

Visits every other week

Extended Treatment Period (ETP)

Continuation of treatment with avalglucosidase alfa to further assess long-term efficacy and safety

52 weeks

Visits every other week

Extended Long-term Treatment Period (ELTP)

Further extended treatment to evaluate long-term outcomes

104 weeks

Visits every other week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• avalglucosidase alfa

Trial Overview 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.

Participant Groups

Group I: Avalglucosidase alfa Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Genzyme, a Sanofi Company

Lead Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Findings from Research

Avalglucosidase alfa (NEXVIAZYME™) is a recombinant enzyme replacement therapy approved in the USA for treating late-onset Pompe disease in patients aged 1 year and older, addressing a critical enzyme deficiency that leads to glycogen accumulation.

The drug has also received a positive opinion in the EU for long-term treatment and is currently under regulatory review in the UK and Japan, indicating its potential for widespread use in managing Pompe disease globally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avalglucosidase alfa: First Approval. Dhillon, S.[2022]

Avalglucosidase alfa, a new treatment for late-onset Pompe disease, was found to be well-tolerated in a study involving 23 patients over 24 weeks, with no deaths or life-threatening adverse events reported.

Exploratory efficacy results showed that patients' pulmonary function and functional capacity remained stable or improved, suggesting that avalglucosidase alfa may be effective in managing symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Pena, LDM., Barohn, RJ., Byrne, BJ., et al.[2020]

In a study of 22 childhood onset Pompe disease patients treated with enzyme replacement therapy (ERT) using recombinant human alpha-glucosidase (rhGAA), 91% developed antibodies against the treatment, but these antibodies did not significantly affect clinical outcomes like muscle strength or pulmonary function.

High antibody titers were linked to infusion-associated reactions (IARs), with 18% of patients experiencing IARs, suggesting that monitoring antibody levels could be important in managing treatment, especially in cases of clinical deterioration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease. van Kooten, HA., Ditters, IAM., Hoogeveen-Westerveld, M., et al.[2022]

The enzyme replacement therapy for Pompe disease, using recombinant human acid alpha-glucosidase (CHO-GAA), was shown to be more effective in reducing glycogen accumulation in the heart compared to skeletal muscle in a mouse model, indicating its potential efficacy in treating the disease.

Biochemical analyses revealed that CHO-GAA had superior binding properties and glycosylation patterns compared to other enzyme variants, which contributed to its selection as the first approved therapy for Pompe disease in multiple countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical and pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe disease. McVie-Wylie, AJ., Lee, KL., Qiu, H., et al.[2021]

In a phase 3 trial involving 100 participants with late-onset Pompe disease, avalglucosidase alfa demonstrated a significant improvement in respiratory function (measured by forced vital capacity) compared to the standard treatment, alglucosidase alfa, with a mean difference of 2.43%.

Avalglucosidase alfa also showed better outcomes in functional endurance (measured by the 6-minute walk test), indicating its potential as a more effective treatment option without new safety concerns compared to the existing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Diaz-Manera, J., Kishnani, PS., Kushlaf, H., et al.[2022]

In the COMET trial extension, patients with late-onset Pompe disease who continued treatment with avalglucosidase alfa showed significant improvements in lung function (FVC percent predicted) and walking distance (6MWT) over 97 weeks, indicating sustained efficacy of the treatment.

No new safety concerns were identified during the extension period, with similar rates of treatment-related adverse events between those who continued avalglucosidase alfa and those who switched from alglucosidase alfa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial. Kishnani, PS., Diaz-Manera, J., Toscano, A., et al.[2023]

Avalglucosidase alfa, an enzyme replacement therapy for late-onset Pompe disease, has been shown to be well tolerated over a period of up to 6.5 years, with no deaths or serious adverse events related to the treatment.

The therapy demonstrated sustained efficacy, as most participants maintained stable lung function and walking ability, with improvements noted in younger participants, indicating its potential long-term benefits for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease. Dimachkie, MM., Barohn, RJ., Byrne, B., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Avalglucosidase alfa: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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]

3. England pubmed.ncbi.nlm.nih.gov

Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Biochemical and pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe disease. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease. [2022]