Shorter Infusion of Fabrazyme for Fabry Disease

(SHORTEN Trial)

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

8 Participants Needed

Trial Summary

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 data supports the idea that Shorter Infusion of Fabrazyme for Fabry Disease is an effective treatment?

The available research shows that Fabrazyme, when used as a treatment for Fabry Disease, has been effective in reducing harmful substances in the body. One study found that regular infusions of Fabrazyme helped clear or reduce these substances in important areas like the kidneys and heart, with results lasting up to five years for most patients. This suggests that the treatment is effective in managing the disease over a long period. Additionally, the treatment has been shown to be safe for patients, even those who had previous allergic reactions, indicating its overall effectiveness and safety. ^{1 2 3 4 5}

What safety data is available for Fabrazyme treatment in Fabry disease?

The safety data for Fabrazyme (agalsidase beta) includes several studies: 1) Successful reinstitution of therapy in patients with previous IgE-antibody or skin-test reactivity, indicating it can be safely continued under certain conditions. 2) Reports of severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies. 3) An international study in pediatric patients showing safety and efficacy. 4) Concerns about increased adverse events at lower dosages during a global enzyme shortage. 5) Long-term safety data from a multicenter phase 3 trial showing stable kidney function, decreased infusion-associated reactions, and reduced antibody titers over 30-36 months of treatment. ^{2 3 6 7 8}

Is the drug Fabrazyme a promising treatment for Fabry Disease?

Yes, Fabrazyme is a promising treatment for Fabry Disease. It helps clear harmful substances from cells, improving kidney, heart, and skin health. It has shown positive results in both adults and children, and can be safely used even in patients with previous allergic reactions. ^{1 2 3 4 9}

What is the purpose of this trial?

This Phase 4 study will evaluate the safety and tolerability of Fabrazyme at current approved dose with increases in the infusion rate and reduced infusion volume. This study aims to generate data to provide the guidance on how infusion rate can be safely increased and minimize the burden of the life-long treatment with Fabrazyme.

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

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]

References

1. England 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. [2023]

2. United States 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. [2016]

3. United States 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. [2022]

4. United States 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. [2022]

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

Comparative evaluation of alpha-galactosidase A infusions for treatment of Fabry disease. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Enzyme therapy in Fabry disease: severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients. [2022]

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

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. [2022]

9. United States 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. [2022]