Elaprase IV Infusion for Hunter Syndrome

No longer recruiting at 8 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how Elaprase treatment (an intravenous infusion) affects growth in children with Hunter syndrome (MPS II), a rare genetic disorder that can cause developmental issues. Researchers will evaluate the treatment's impact by focusing on changes in height and weight. The trial includes two groups of boys: one group receiving Elaprase for the first time and another whose past growth data will be analyzed. Boys who haven't had Elaprase before and have a confirmed Hunter syndrome diagnosis might be a good fit for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand how it benefits more patients.

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 is the safety track record for Elaprase?

Research has shown that Elaprase, a treatment for Hunter syndrome, has undergone safety testing in several studies. In one study lasting 53 weeks with 96 patients, researchers compared Elaprase to a placebo. The results indicated it was generally well-tolerated. Some patients experienced mild to moderate side effects, such as headaches and fever, but these were not severe or life-threatening.

Elaprase has already received FDA approval for treating Hunter syndrome, indicating it has undergone thorough testing to ensure safety for this condition. However, individual reactions can differ. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Elaprase is unique because it specifically targets the underlying enzyme deficiency in Hunter Syndrome. This treatment delivers a synthetic version of the enzyme iduronate-2-sulfatase, which patients with Hunter Syndrome lack. By directly replacing the missing enzyme, Elaprase helps break down complex sugars in the body, potentially reducing symptoms and improving quality of life. Researchers are excited about Elaprase because it offers a targeted approach to managing Hunter Syndrome that directly addresses the root cause of the disease, rather than merely alleviating symptoms.

What is the effectiveness track record for Elaprase in treating Hunter syndrome?

Research has shown that Elaprase, the treatment under study in this trial for Hunter syndrome, performs well in several studies. Data from the Hunter Outcome Survey found that patients taking Elaprase showed improved growth in height and weight. Another study found that Elaprase safely and effectively treats key physical symptoms of Hunter syndrome. The treatment is approved in the USA and EU, indicating its potential to slow the disease. Overall, the evidence supports Elaprase as a valuable treatment for managing Hunter syndrome. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

Shire

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7173756/

Enzyme replacement therapy with idursulfase for ... The effect of idursulfase on growth in patients with Hunter syndrome: data from the Hunter Outcome Survey (HOS). Molecular Genetics and Metabolism 2013;109 ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2006/125151s0000_Elaprase_StatR.pdf

Statistical Review(s) - accessdata.fda.gov This reviewer concludes that the statistical results of the Phase 2/3 study in patients with Hunters syndrome support the applicant's conclusion that ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1098360025001078

Efficacy and safety of idursulfase beta in the treatment ... Idursulfase beta is a safe and effective treatment option in mucopolysaccharidosis II, addressing crucial somatic ailments presented by patients.

4. jpeds.com jpeds.com/article/S0022-3476(22)00414-0/fulltext

Effect of Anti-Iduronate 2-Sulfatase Antibodies in Patients ... The results indicate that a titer starting at 1:2560 (as seen in patient 2) can already neutralize elaprase to such extent that uDS and uHS ...

5. openaccessjournals.com openaccessjournals.com/articles/idursulfase-for-enzymereplacement-therapy-in-mucopolysaccharidosis-ii.pdf

Idursulfase for enzyme-replacement therapy in ... Idursulfase is now approved in the USA and EU and may offer the opportunity to affect the progression of Hunter disease in treated patients.

6. elaprase.com elaprase.com/hcp/faqs/

healthcare professional faqs ELAPRASE is indicated for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II ). ELAPRASE has been shown to improve walking capacity in patients 5 ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2006/125151s0000_Elaprase_MedR.pdf

BLA STN 125151 Elaprase (idursulfase) - CPY Document - FDA Elaprase has been evaluated in patients with Hunter syndrome (also known as Mucopolysaccharidosis II, or MPS II), an X-linked recessive disease ...

8. elaprase.com elaprase.com/Content/pdf/ELAPRASE%20PI.pdf

FULL PRESCRIBING INFORMATION The safety and efficacy of ELAPRASE were evaluated in a 53-week, randomized, double-blind, placebo-controlled clinical trial of 96 patients with Hunter syndrome ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10826424/

Intrathecal idursulfase-IT in patients with neuronopathic ... Two-thirds of patients with mucopolysaccharidosis II (MPS II; Hunter syndrome) have cognitive impairment. This phase 2/3, randomized, controlled, ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT01506141

An Extension Study of HGT-HIT-045 Evaluating Long-Term ... This extension study of HGT-HIT-045 is designed to collect long-term safety data in pediatric participants with Hunter syndrome and cognitive impairment who ...