Avalglucosidase Alfa for Pompe Disease

(Mini-COMET Trial)

Not currently recruiting at 24 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Genzyme, a Sanofi Company

Must be taking: Alglucosidase alfa

Must not be taking: Immune modulatory treatment

Disqualifiers: High antibody titer, Severe allergy risk, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 25 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, avalglucosidase alfa, for children with Infantile-Onset Pompe Disease (IOPD), a rare condition affecting muscles and organs. The trial aims to determine if avalglucosidase alfa can benefit those who have already used another treatment, alglucosidase alfa, without sufficient improvement. Participants will receive varying doses of avalglucosidase alfa to identify the most effective one. Children under 18 who have been on the previous treatment for at least six months and have experienced a decline in symptoms are suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that certain medications, like immune modulatory treatments, are not allowed during the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that avalglucosidase alfa is generally well-tolerated at all doses, with no deaths or life-threatening serious side effects reported. Most side effects were mild and manageable. Some patients might experience infusion-related reactions, common with this type of treatment, such as chills, fever, or headache during or after the infusion.

Alglucosidase alfa has also been studied for safety in patients with Pompe disease, showing no major safety concerns. Patients are usually monitored during and after infusions to ensure safety. Both treatments have been used in different forms of Pompe disease, providing reassurance about their safety.

Since this trial is in Phase 2, the treatment has already passed initial safety tests in humans. This phase focuses on finding the right dose and further assessing safety. Reaching this stage without major safety issues is a positive sign. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about avalglucosidase alfa for treating Pompe disease because it offers a potentially more effective enzyme replacement therapy. Unlike the current standard, alglucosidase alfa, avalglucosidase alfa is designed to enhance the delivery of the enzyme to muscle tissues, where it's most needed. This targeted delivery could lead to improved muscle function and overall better outcomes for patients. Additionally, the treatment explores different dosing regimens, such as 20 mg/kg and 40 mg/kg, to find the optimal balance between efficacy and safety, which may provide more tailored options for patients.

What evidence suggests that this trial's treatments could be effective for Infantile-Onset Pompe Disease?

Research shows that avalglucosidase alfa holds promise for treating Pompe disease. In this trial, participants will receive varying dosages of avalglucosidase alfa or alglucosidase alfa. Studies have found that patients using avalglucosidase alfa experienced good health outcomes over time. This treatment also proved more effective at lowering disease-related markers compared to alglucosidase alfa. Previous studies on alglucosidase alfa demonstrated improvements in heart function and survival in young children with Pompe disease. However, recent comparisons suggest avalglucosidase alfa might be more effective, potentially offering better long-term benefits. ^{1 5 6 7 8}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for children under 18 with infantile-onset Pompe disease who've been on alglucosidase alfa for at least 6 months. They must show signs of the disease worsening or not improving enough, and be able to follow the study plan. Pregnant or breastfeeding females can't join, nor those allergic to the study drugs or on certain other medications.

Inclusion Criteria

I am of legal age or have consent from my guardian to participate.

I have Pompe Disease and my breathing, movement, or heart health is getting worse.

I (and my guardian, if I'm a minor) can follow the study's requirements.

Exclusion Criteria

I am using effective birth control or am willing to be tested for pregnancy.

You are at high risk for a severe allergic reaction to neoGAA (avalglucosidase alfa).

I have high antibody levels against alglucosidase alfa.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avalglucosidase alfa or alglucosidase alfa via IV infusion every other week for 25 weeks

25 weeks

Extension Treatment

Participants continue to receive avalglucosidase alfa IV infusion every other week

Up to 430 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• alglucosidase alfa GZ419829
• avalglucosidase alfa GZ402666

Trial Overview The trial tests avalglucosidase alfa's safety and effectiveness in kids previously treated with alglucosidase alfa for Pompe Disease. It compares how both drugs work in the body (pharmacokinetics) and their impact on symptoms like heart size, muscle function, breathing, and eyelid drooping.

How Is the Trial Designed?

Group I: Cohort 3b: Alglucosidase Alfa in PAP Experimental Treatment 2 Interventions

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 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.

Group II: Cohort 3a: Avalglucosidase Alfa 40 mg//kg Experimental Treatment 1 Intervention

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.

Group III: Cohort 2: Avalglucosidase Alfa 40 mg/kg Experimental Treatment 1 Intervention

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.

Group IV: Cohort 1: Avalglucosidase Alfa 20 mg/kg Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33543425/

STIG study: real-world data of long-term outcomes of adults ... The STIG real-world study confirms an initial efficacy of ERT in the first years with a secondary sustained decline in multiple outcome measures.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3129995/

Early Treatment with Alglucosidase Alfa Prolongs Long Term ... In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 ...

3. 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 ...

4. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-023-02981-2

Higher dose alglucosidase alfa is associated with improved ... Higher ALGLU doses were associated with significantly improved overall and invasive ventilator-free survival in IOPD. Results were consistent ...

5. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1310317/full

Efficacy and safety of enzyme replacement therapy with ... Our data suggest that alglucosidase alfa potentially improves LV mass, TSV, and survival in IOPD patients, with no important safety issues.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa0909859

A Randomized Study of Alglucosidase Alfa in Late-Onset ... Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0960896617314633

Safety, tolerability, pharmacokinetics, pharmacodynamics, ... Avalglucosidase alfa (neoGAA) had a well-tolerated safety profile in LOPD patients. Respiratory and functional capacities were stable or improved in most ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00158600

NCT00158600 | A Placebo-Controlled Study of Safety and ... The overall objective is to evaluate the safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa treatment in patients with late-onset Pompe disease ...