Shorter Infusion of Fabrazyme for Fabry Disease

(SHORTEN Trial)

No longer recruiting at 4 trial locations

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

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Sanofi

Must be taking: Fabrazyme

Must not be taking: Diphenhydramine, Loratadine, others

Disqualifiers: Pregnancy, Breastfeeding, Allergic disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a faster and easier method of administering Fabrazyme, a treatment for Fabry Disease, by observing patient reactions to a shorter infusion time. The goal is to determine if a quicker infusion can safely reduce the inconvenience of lifelong treatment. The trial seeks individuals with Fabry Disease who have used Fabrazyme for at least three months without recent treatment issues. Eligible participants can be female or male, must weigh more than 30 kg, and have a confirmed diagnosis of Fabry Disease. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment can benefit more patients, potentially improving the treatment experience.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have a contraindication to Fabrazyme or any premedications like diphenhydramine, acetaminophen, montelukast, or dexamethasone.

What is the safety track record for Fabrazyme?

Research has shown that Fabrazyme, a treatment for Fabry disease, is generally safe. A detailed review found that altering the infusion duration did not cause major safety issues, indicating the drug is well-tolerated even with different administration methods.

Fabrazyme has been used for 20 years, with substantial real-world evidence supporting its safety and effectiveness. One study followed patients for over 30 months and confirmed the treatment's safety and effectiveness over time.

Overall, these findings suggest that Fabrazyme is generally safe for those who need it. However, like any treatment, monitoring by healthcare professionals is important during its use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Fabrazyme is unique because it's being tested for a shorter infusion time, which could make life much easier for people with Fabry disease. Typically, treatments like enzyme replacement therapies for Fabry disease require lengthy infusion sessions that can be time-consuming and inconvenient. Researchers are excited about Fabrazyme because if successful, it could significantly reduce the time patients spend receiving treatment, enhancing their quality of life without compromising effectiveness. This potential change in the delivery method is what sets Fabrazyme apart from other options.

What is the effectiveness track record for Fabrazyme in treating Fabry Disease?

Research has shown that Fabrazyme effectively treats Fabry disease. A long-term study found that patients taking agalsidase beta, the main ingredient in Fabrazyme, remained healthy and avoided major health problems for over ten years. Another study shows that Fabrazyme helps slow kidney and heart issues related to Fabry disease. Fabrazyme is the only enzyme replacement therapy approved by the FDA for this condition, with strong evidence supporting its safety and effectiveness over time. Most patients also report experiencing less pain from Fabry disease while on this treatment. ^{3 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for individuals with Fabry Disease, including those new to enzyme replacement therapy (ERT-naïve) and others previously treated with Fabrazyme. Participants must be between 2-65 years old and meet specific weight criteria. Women who can have children must use effective birth control. People cannot join if they've had infusion reactions to Fabrazyme in their last three treatments.

Inclusion Criteria

I am a male over 30kg, treated with Fabrazyme for 3+ months without infusion reactions recently.

I am a woman over 30kg, treated with Fabrazyme for 3+ months without reactions to the last 3 doses.

I am a male over 30kg, treated with Fabrazyme for 3+ months without infusion reactions recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive agalsidase beta 1 mg/kg infusion once every other week with increased infusion rate and reduced infusion volume

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fabrazyme

Trial Overview The study tests whether increasing the rate of infusing Fabrazyme, a treatment for Fabry Disease, while reducing its volume is safe and tolerable. It aims to make this lifelong treatment less burdensome by shortening the time patients spend receiving it.

How Is the Trial Designed?

Group I: agalsidase beta Experimental Treatment 8 Interventions

agalsidase beta 1 mg/kg infusion once every other week

Fabrazyme is already approved in United States, European Union for the following indications:

Approved in United States as Fabrazyme for:

• Fabry disease in adults and pediatric patients 2 years of age and older

Approved in European Union as Fabrazyme for:

• Fabry 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

Published Research Related to This Trial

Enzyme replacement therapy with agalsidase beta can be safely continued in Fabry disease patients who previously had allergic reactions, as shown in a study with six male participants aged 26-66.

During the rechallenge, no anaphylactic reactions occurred, and while some mild to moderate adverse events were reported, they were manageable, allowing all patients to transition to commercial treatment after the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme. Bodensteiner, D., Scott, CR., Sims, KB., et al.[2022]

In a study involving 16 pediatric patients with Fabry disease, enzyme replacement therapy with agalsidase beta effectively cleared harmful GL-3 accumulation in skin cells after 24 weeks of treatment, demonstrating its efficacy in managing the disease.

The treatment was generally well tolerated, with most side effects being mild to moderate, and it also led to a decrease in gastrointestinal symptoms and school absences, indicating a positive impact on the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. Wraith, JE., Tylki-Szymanska, A., Guffon, N., et al.[2016]

A post-marketing analysis of 2,678 infusions of agalsidase beta for Fabry disease showed that reducing infusion duration to less than 90 minutes did not significantly impact safety outcomes, with serious adverse events occurring in only 0.6% of cases.

Infusion-associated reactions (IARs) and adverse events (AEs) were numerically lower with shorter infusion times, suggesting that patients who tolerate treatment may benefit from gradually decreasing infusion durations under careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of agalsidase beta infusions shorter than 90 min in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study. Lee, CS., Tsurumi, M., Eto, Y.[2023]

In a study involving 21 adult males with Fabry disease, a lower dose of agalsidase beta (0.3 mg/kg every 2 weeks) was able to maintain globotriaosylceramide clearance achieved with a higher dose (1.0 mg/kg) in 90% of patients after 6 months of treatment.

While the lower dose maintained globotriaosylceramide reduction in about 70% of other renal cell types and dermal capillaries, the long-term clinical effects of this dose reduction have not yet been assessed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Lubanda, JC., Anijalg, E., Bzdúch, V., et al.[2022]

In a study involving 34 patients with Fabry disease, both agalsidase alfa and agalsidase beta showed no significant difference in reducing left ventricular mass or other disease parameters after 12 and 24 months of treatment at a dose of 0.2 mg/kg biweekly.

Treatment failure occurred in 8 out of 34 patients, with no significant difference between the two enzyme preparations, suggesting that factors like age and severity of pre-treatment disease may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. Vedder, AC., Linthorst, GE., Houge, G., et al.[2022]

A hemizygous male patient with Fabry disease experienced severe anaphylactoid shock after receiving agalsidase beta, indicating a serious adverse reaction to enzyme replacement therapy.

Despite negative immunological tests for specific IgE antibodies and skin reactivity, the patient had repeated anaphylactoid shock episodes, highlighting that such tests do not eliminate the risk of severe allergic reactions to agalsidase infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme therapy in Fabry disease: severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies. Tesmoingt, C., Lidove, O., Reberga, A., et al.[2022]

During the shortage of agalsidase beta for Fabry disease treatment, the incidence of clinical events in 35 Dutch patients remained unchanged, indicating that the reduced dosage or switch to agalsidase alpha did not lead to more health complications.

However, there was a significant increase in the biochemical marker lysoGb3 in males after one year of the shortage, suggesting a potential recurrence of disease activity despite stable clinical event rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients. Smid, BE., Rombach, SM., Aerts, JM., et al.[2022]

In a 30-36 month extension study of 58 patients with Fabry disease, treatment with recombinant human alpha-galactosidase A (agalsidase beta) resulted in continuously normal plasma globotriaosylceramide (GL-3) levels and sustained clearance of GL-3 from capillary endothelial cells in 98% of patients, indicating long-term efficacy.

The treatment demonstrated a favorable safety profile, with a decrease in infusion-related reactions and anti-rh-alpha GalA IgG antibody levels over time, suggesting that patients can tolerate the therapy well even after developing antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Wilcox, WR., Banikazemi, M., Guffon, N., et al.[2022]

Enzyme therapy has been shown to be safe and effective in treating Gaucher disease, and similar approaches are now being explored for Fabry disease with the products agalsidase alpha and beta.

Comparative analysis of pivotal trials for these treatments highlights the need for long-term data to fully assess their efficacy and safety, as short-term trials may not capture the outcomes for chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of alpha-galactosidase A infusions for treatment of Fabry disease. Hopkin, RJ., Bissler, J., Grabowski, GA.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4413801/

Ten-year outcome of enzyme replacement therapy with ... This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease. Most patients remained alive and event-free.

2. academic.oup.com academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfaf318/8286902

Clinical outcomes in Fabry Patients switching to agalsidase ... This study was aimed to assess the effects of switching to agalsidase beta for renal ineffectiveness of the primary Fabry therapy. Methods. Data ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2214426925000308

Two decades of experience of the Fabry Outcome Survey ... These results indicate that treatment with agalsidase alfa slowed renal deterioration and progression of cardiomyopathy, and delayed morbidity and death in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1182009/

Long-Term Safety and Efficacy of Enzyme Replacement ... In addition, most patients report decreased and/or less-frequent Fabry pain, but these findings have varied among patients. Clearly, additional experience is ...

5. news.sanofi.us news.sanofi.us/2021-03-12-Long-term-data-on-Fabrazyme-R-agalsidase-beta-for-people-with-Fabry-disease

Fabrazyme is the only FDA-approved enzyme replacement ... Fabrazyme is the only FDA-approved enzyme replacement therapy for Fabry disease with long-term efficacy and safety data.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10367408/

Safety and tolerability of agalsidase beta infusions shorter ... The results of this post-hoc analysis demonstrated no significant impact of infusion duration on safety outcomes, and no significant difference in outcomes ...

7. pro.campus.sanofi pro.campus.sanofi/us/products/fabrazyme/real-world-patient-experience

Fabrazyme® 20 Years of Real-World Experience Explore 20 years of real-world experience with historical data for Fabry disease, including long-term safety & efficacy info on Fabrazyme® (agalsidase ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00074984

NCT00074984 | A Study of the Safety and Efficacy ... The primary efficacy endpoint was the time to the first occurrence of a clinically significant renal (33% increase in serum creatinine, dialysis or transplant), ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1096719222004437

Clinical outcomes among young patients with Fabry ... Our aim was to analyze clinical outcomes among patients aged 5–30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry.