Elaprase IV Infusion for Hunter Syndrome

Recruiting at 7 trial locations

Age: < 18

Sex: Male

Trial Phase: Phase 4

Sponsor: Shire

Must not be taking: Investigational drugs, Idursulfase-IT, Growth hormones

Disqualifiers: Blood transfusions, Non-compliance, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5-10 years

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received certain treatments like investigational drugs, idursulfase-IT, growth hormones, or blood transfusions recently. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Elaprase (idursulfase) for treating Hunter syndrome?

Research shows that Elaprase (idursulfase) helps people with Hunter syndrome by increasing their walking distance, improving lung function, and reducing the size of organs and certain substances in the urine. It is generally well tolerated, although some people may experience reactions during the infusion. ^{1 2 3 4 5}

Is Elaprase (idursulfase) safe for humans?

Elaprase (idursulfase) is generally well tolerated in humans, though some people may experience mild infusion reactions, such as allergic reactions or cough. Serious adverse events are rare and not typically related to the treatment. ^{1 3 6 7 8}

How is the drug Elaprase unique in treating Hunter syndrome?

Elaprase is unique because it is the first enzyme replacement therapy specifically approved for Hunter syndrome, addressing the root cause by replacing the deficient enzyme iduronate-2-sulfatase. It is administered through weekly infusions and has been shown to improve walking distance, lung function, and reduce organ size and harmful substances in the body. ^{1 3 8 9 10}

What is the purpose of this trial?

This long-term study will provide Elaprase treatment to children enrolled in this study and will utilize data from both enrolled patients and Hunter Outcome Survey (HOS) patient registry data to conduct the primary growth analysis to assess changes in height and weight in patients with Mucopolysaccharidosis II (Hunter syndrome) MPS II.

Research Team

Study Director

Principal Investigator

Shire

Eligibility Criteria

This trial is for boys under 6 with Hunter syndrome (MPS II) who haven't had Elaprase before. They must have a confirmed diagnosis and agree to data collection. Boys can't join if they've had blood transfusions, growth treatments, or other recent investigational drugs.

Inclusion Criteria

I am a male patient.

I have been receiving Elaprase treatment weekly for at least 5 years.

My height and weight were recorded around the time I started Elaprase treatment.

Exclusion Criteria

I have received a blood transfusion in the last 90 days.

I have not taken growth hormone or similar treatments to promote growth.

I am currently being treated with or have been treated with idursulfase-IT.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Long-term Elaprase treatment for children with MPS II

5-10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Elaprase

Trial Overview The study tests the long-term effects of Elaprase IV infusions on height and weight in young boys with MPS II. It combines new patient data with existing records from the Hunter Outcome Survey to analyze growth patterns.

Participant Groups

Group I: Enrolled Patients Experimental Treatment 1 Intervention

Patients who are receiving treatment with Elaprase in this study (SHP-ELA-401), who are \<6 years of age, and were previously treatment-naïve. Patients who are not enrolled in this study (SHP-ELA-401) but are enrolled in the Hunter Outcome Survey (HOS) patient registry and were \< 6 years of age at start of Elaprase treatment. While not enrolled in the present Study SHP-ELA-401, their height and weight data from HOS will be utilized in the Primary Growth Analysis for this study.

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

Approved in United States as Elaprase for:

• Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Approved in European Union as Elaprase for:

• Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Approved in Canada as Elaprase for:

• Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Who Is Running the Clinical Trial?

Shire

Lead Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Findings from Research

Idursulfase (Elaprase) is the first approved enzyme replacement therapy for Hunter syndrome, showing significant benefits in a phase II/III clinical trial, including increased walking distance, improved pulmonary function, and reduced organ size and urinary glycosaminoglycans (GAGs) excretion in patients.

The treatment is generally well tolerated, although some patients may experience infusion reactions, marking idursulfase as a promising symptomatic therapy that addresses the underlying enzymatic deficiency in Hunter syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idursulfase in Hunter syndrome treatment. Zareba, G.[2017]

Long-term enzyme replacement therapy with idursulfase for Hunter syndrome showed sustained clinical improvements over 3 years, including a 25.1% increase in absolute forced vital capacity and significant enhancements in walking distance.

While 53% of patients experienced infusion-related adverse events, these decreased over time, and the presence of neutralizing antibodies in 23% of patients was associated with reduced pulmonary function improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Muenzer, J., Beck, M., Eng, CM., et al.[2022]

Enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has shown positive effects in patients of all ages, including improvements in weight, height, and a significant reduction in glycosaminoglycan (GAG) levels, which are associated with the disease.

The therapy led to notable clinical improvements, such as recovery from carpal tunnel syndrome and decreased organomegaly, particularly in one patient who experienced an 86% reduction in GAGs, highlighting the efficacy of ERT in managing symptoms and preventing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome. Dalmau Serra, J., Vitoria Miñana, I., Calderón Fernández, R., et al.[2015]

Idursulfase-IT, administered monthly, was generally well tolerated in 56 patients over a 36-month period, with only 25% experiencing mild adverse events and no serious adverse events linked to the treatment.

Secondary analyses suggested a potential cognitive benefit for younger patients with specific genetic variants, indicating that idursulfase-IT may help improve cognitive function in some children with MPS II, although the overall evidence was deemed insufficient for regulatory approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II. Muenzer, J., Burton, BK., Harmatz, P., et al.[2023]

Enzyme replacement therapy (ERT) with idursulfase beta has shown significant improvements in symptoms and quality of life for patients with MPS II, despite the risk of infusion-associated reactions (IARs).

Discontinuation of ERT due to recurrent IARs can lead to worsening clinical symptoms, highlighting the importance of continuing treatment whenever possible, as demonstrated in two adolescent patients who successfully managed their reactions with idursulfase beta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term experience with idursulfase beta (Hunterase) in two adolescent patients with MPS II: A case series. Chan, MY., Nelson, AJ., Ngu, LH.[2023]

Idursulfase beta has a significantly higher formylglycine (FGly) content and specific enzyme activity compared to idursulfase, which may enhance its effectiveness in treating Mucopolysaccharidosis II (Hunter syndrome).

The study suggests that the differences in enzyme activity could impact clinical outcomes, but further long-term evaluations in patients are necessary to confirm these potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome. Chung, YK., Sohn, YB., Sohn, JM., et al.[2021]

In a phase I/II trial involving 31 patients with MPS II, treatment with idursulfase beta resulted in a significant reduction of urinary glycosaminoglycan (GAG) levels, indicating effective clearance of the accumulated substance associated with the disorder.

Idursulfase beta also improved endurance as shown by the 6-minute walk test, and it was generally safe with manageable side effects, primarily mild skin reactions that were easily treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter syndrome). Sohn, YB., Cho, SY., Park, SW., et al.[2021]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Idursulfase in Hunter syndrome treatment. [2017]

2. Denmark pubmed.ncbi.nlm.nih.gov

IgE-mediated anaphylaxis and allergic reactions to idursulfase in patients with Hunter syndrome. [2019]

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

Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome. [2015]

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

Home treatment in paediatric patients with Hunter syndrome: the first Italian experience. [2021]

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

Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II. [2023]

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

Safety and efficacy of enzyme replacement therapy with idursulfase beta in children aged younger than 6 years with Hunter syndrome. [2015]

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

Long-term experience with idursulfase beta (Hunterase) in two adolescent patients with MPS II: A case series. [2023]

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

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter syndrome). [2021]