ELAPRASE + Prophylactic Therapy for Hunter Syndrome

Recruiting at 10 trial locations

Age: < 18

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Takeda

Must be taking: Elaprase

Must not be taking: Growth hormones

Disqualifiers: Investigational drug, Growth hormones, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main aim of this study is to evaluate the ability of a prophylactic immune tolerizing regimen (ITR) to prevent or reduce the development of high titer anti-idursulfase antibodies in treatment-naïve participants with Hunter syndrome. In this open label, single arm study, all participants will receive ELAPRASE treatment and a prophylactic ITR. Participants will be treated with ELAPRASE for up to 104 weeks. The prophylactic ITR will start 1 day prior to the start of ELAPRASE. The prophylactic ITR will consist of a 5-week cycle of: Rituximab (intravenously \[IV\], weekly for 4 weeks); Methotrexate (oral, 3 times per week for 5 weeks) and intravenous immunoglobulin (IVIG) (IV, every 4 weeks of the cycle). Following the completion of 1 cycle, an assessment will be made at Month 6, 12, and 18 regarding the need for administering another 5-week cycle of the ITR. Participants will be in the study for approximately 112 weeks (including 6 weeks for screening, up to 104 weeks for treatment, and 2 weeks for follow-up).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it excludes participants who are currently using any medication that could affect the study. It's best to discuss your current medications with the study team to see if they might impact your eligibility.

What data supports the effectiveness of the drug ELAPRASE for Hunter Syndrome?

Research shows that ELAPRASE (idursulfase) helps people with Hunter syndrome by increasing their ability to walk, 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 infusions. ^{1 2 3 4 5}

Is the treatment with ELAPRASE (idursulfase) generally safe for humans?

ELAPRASE (idursulfase) is generally well tolerated in humans, although some people may experience infusion reactions, which are side effects that occur during or after the drug is given. Serious allergic reactions can happen, and up to 50% of patients may develop antibodies against the treatment, but these are not common. ^{3 5 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 missing enzyme iduronate-2-sulfatase. This treatment helps improve symptoms like walking distance and lung function, and reduces organ size and harmful substances in the body. ^{1 2 4 5 9}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for treatment-naïve boys under 6 with Hunter syndrome, having specific enzyme deficiencies and gene mutations. They must not have used ELAPRASE or certain other treatments recently and should be able to follow the study protocol without any medical conditions that could interfere.

Inclusion Criteria

I have been diagnosed with MPS II.

Your enzyme activity levels for certain substances in your body are within the normal range.

You do not have antibodies against the drug idursulfase in your blood.

Exclusion Criteria

Within 30 days prior to the first dose of investigational product, the participant has been enrolled in a clinical study that may impact this study

I am not on any medication that could interfere with the study.

Participant has received treatment with any investigational drug within the 30 days prior to study entry

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive ELAPRASE treatment and a prophylactic immune tolerizing regimen (ITR) for up to 104 weeks. The ITR includes Rituximab, Methotrexate, and IVIG in a 5-week cycle.

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• ELAPRASE (Enzyme Replacement Therapy)
• Intravenous Immunoglobulin (IVIG) (Immunoglobulin)
• Methotrexate (Immunosuppressant)
• Rituximab (Immunomodulator)

Trial Overview The study tests if a preventive immune regimen can stop or lessen high titer anti-idursulfase antibodies in patients taking ELAPRASE. It includes Rituximab, Methotrexate, IVIG alongside ELAPRASE over up to 104 weeks with assessments every six months.

Participant Groups

Group I: ITR + ELAPRASE Experimental Treatment 4 Interventions

Participants will receive prophylactic ITR which consist of rituximab, methotrexate and IVIG in a 5-week cycle. Following the completion of 1 cycle and at the Month 6, 12, and 18 study visits, an assessment will be made regarding the need for administering another 5-week cycle of the ITR depending on the trend of the participants anti-idursulfase antibody titers and lymphocyte quantitation and CD19 percent (%) recovery. Elaprase treatment (IV, weekly) will start 1 day after the initiation of the first cycle of ITR and continue for 104 weeks. The dose of ELAPRASE will be calculated based on the participant's weight at each visit.

Who Is Running the Clinical Trial?

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

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]

The study developed specific polyclonal antibodies against human iduronate 2-sulphate sulphatase (IDS), which can be used to detect and quantify IDS in fermentation extracts from Pichia pastoris and Escherichia coli, crucial for enzyme replacement therapy in Hunter syndrome.

These antibodies are effective in distinguishing IDS from other proteins, allowing for their application in both an ELISA system for quantification and in affinity chromatography for purification, enhancing the potential for developing effective treatments for Hunter syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Production of polyclonal antibodies to protein iduronate-2-sulphate sulphatase (IDS) and development of a detection system for human recombinant IDS]. Peña, O., Sosa, A., Echeverri, O., et al.[2007]

In a study of 124 patients with Hunter syndrome who started enzyme replacement therapy with idursulfase before the age of 6, treatment was found to be safe, with no new safety concerns identified, despite 26.6% experiencing infusion-related reactions.

The therapy demonstrated effectiveness, as evidenced by a significant reduction in urine glycosaminoglycan levels and liver size after at least 6 months of treatment, indicating clinical benefits for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. Muenzer, J., Beck, M., Giugliani, R., et al.[2022]

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]

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 shows beneficial effects in young children under 5 years with Hunter syndrome, including reduced urinary GAG levels and stabilization or improvement in joint mobility after 6 to 14 months of treatment.

The treatment also helped maintain normal height growth and reduced organ size in some patients, suggesting that ERT is effective and safe for this age group, although more studies are needed for direct comparisons with older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS). Alcalde-Martín, C., Muro-Tudelilla, JM., Cancho-Candela, R., et al.[2022]

In a study involving 28 boys aged 1.4 to 7.5 years with Hunter syndrome, idursulfase was found to be generally safe, with most adverse events being mild or moderate, although 57% reported treatment-related adverse events.

Idursulfase treatment led to a decrease in organ size and urinary glycosaminoglycan levels, indicating potential efficacy, while growth rates and developmental quotients remained stable, similar to outcomes seen in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4-7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy. Giugliani, R., Hwu, WL., Tylki-Szymanska, A., et al.[2022]

Enzyme replacement therapy (ERT) with idursulfase beta has been shown to be effective and well-tolerated in a 13-year-old patient with attenuated MPS II, especially after experiencing adverse reactions to idursulfase.

Both idursulfase and idursulfase beta are approved treatments for MPS II, but idursulfase beta may offer a safer alternative for patients who develop infusion-related reactions to idursulfase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II. Ngu, LH., Ong Peitee, W., Leong, HY., et al.[2022]

In a study of 32 Korean patients with Hunter syndrome receiving enzyme replacement therapy (ERT) for at least 2 years, significant growth improvements were observed, particularly in younger patients starting treatment before age 6.

The study indicated that ERT may have a reduced effect on growth in older patients, especially those with more severe forms of Hunter syndrome, suggesting that early intervention could be crucial for better growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of enzyme replacement therapy on linear growth in Korean patients with mucopolysaccharidosis type II (Hunter syndrome). Cho, SY., Huh, R., Chang, MS., et al.[2021]

References

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

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

2. Colombia pubmed.ncbi.nlm.nih.gov

[Production of polyclonal antibodies to protein iduronate-2-sulphate sulphatase (IDS) and development of a detection system for human recombinant IDS]. [2007]

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

Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. [2022]

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

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

5. Spain pubmed.ncbi.nlm.nih.gov

Idursulfase in Hunter syndrome treatment. [2017]

6. Netherlands pubmed.ncbi.nlm.nih.gov

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS). [2022]

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

A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4-7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy. [2022]

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

Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Impact of enzyme replacement therapy on linear growth in Korean patients with mucopolysaccharidosis type II (Hunter syndrome). [2021]