Avalglucosidase Alfa for Pompe Disease

(Baby-COMET Trial)

Not currently recruiting at 43 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of avalglucosidase alfa, a treatment for infantile-onset Pompe disease (IOPD), a rare genetic disorder affecting the muscles and heart. Participants will receive the treatment through an IV every two weeks. The trial seeks individuals with a confirmed diagnosis of IOPD who have not yet received any specific treatment for this condition. Participants should also have cardiomyopathy, a common heart condition in Pompe disease. The study will last up to four years, requiring frequent visits. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising treatment.

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.

Is there any evidence suggesting that avalglucosidase alfa is likely to be safe for humans?

Research has shown that avalglucosidase alfa is generally well-tolerated. In one study, patients who used avalglucosidase alfa for up to 97 weeks experienced improved breathing and movement. Another study found that patients maintained stable breathing and movement after switching to this treatment. These results suggest that avalglucosidase alfa is safe, as participants did not experience major negative effects. Avalglucosidase alfa has demonstrated positive results in treating Pompe disease, supporting its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Avalglucosidase alfa is unique because it offers a new approach to treating Pompe disease by replacing the enzyme that patients lack. Unlike standard treatments like alglucosidase alfa, avalglucosidase alfa is designed to improve the delivery and uptake of the enzyme into muscle tissue, potentially enhancing its effectiveness. Researchers are excited because this could mean better outcomes for patients, such as improved muscle function and reduced disease progression.

What evidence suggests that avalglucosidase alfa might be an effective treatment for Pompe disease?

Research has shown that avalglucosidase alfa, the treatment under study in this trial, may help treat Pompe disease, particularly by improving lung function. One study found that patients experienced over a 10% improvement in their ability to breathe deeply after 97 weeks. Additionally, avalglucosidase alfa proved more effective than alglucosidase alfa, an existing treatment, in lowering disease-related markers. This suggests that avalglucosidase alfa might better manage Pompe disease symptoms. Overall, these findings support its potential effectiveness in treating the condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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, 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40817977/

Efficacy and safety of avalglucosidase alfa in patients with ... Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38313679

Real-world outcomes from a series of patients with late ... This study presents evidence that switching from alglucosidase to avalglucosidase may be associated with improved outcomes in certain patients with LOPD.

3. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2802973

Efficacy and Safety of Avalglucosidase Alfa in Patients With ... At 97 weeks, FVC percent predicted improved by more than 10% in 16 patients and worsened by more than 10% in 14 patients (eFigure 1 in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1098360025000206

Article Efficacy of transitioning from alglucosidase alfa to ... In this study, AVA demonstrated superior efficacy compared with AGL in reducing the levels of Pompe disease-related biomarker levels. This finding aligns with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01898364

NCT01898364 | Safety and Efficacy Evaluation of Repeat ... Primary Objective: To evaluate the safety and tolerability of neoGAA in treatment naïve and alglucosidase alfa treated late-onset Pompe disease patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10087094/

Efficacy and Safety of Avalglucosidase Alfa in Patients With ... In the COMET trial extension period, participants treated with avalglucosidase alfa for up to 97 weeks maintained improvements in respiratory ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S221442692400079X

Avalglucosidase alfa in infantile-onset Pompe disease Enzyme replacement therapy with alglucosidase alfa (rhGAA) has been available since 2006 and patients treated with the enzyme show improved outcomes.

8. sanofi.com sanofi.com/en/media-room/press-releases/2024/2024-02-05-23-00-00-2823915

Media Update: New data demonstrate clinical safety, ... Results showed that patients who switched to avalglucosidase alfa had stabilized respiratory function and mobility, as measured by upright ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36542086/

Safety and efficacy of avalglucosidase alfa in individuals ... These data support the positive clinical effect of avalglucosidase alfa in patients with infantile-onset Pompe disease previously declining on alglucosidase ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1096719223007515

Meaningful change analyses from the Phase 3 COMET trial These analyses show that avalglucosidase alfa improves multiple symptoms and aspects of daily functioning, including breathing and mobility.