Idursulfase-IT + Elaprase for Hunter Syndrome

Not currently recruiting at 6 trial locations

Overseen By Takeda Contact

Age: < 65

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Takeda

Must be taking: Idursulfase-IT, Elaprase

Disqualifiers: Seizure disorder, Bleeding disorder, Hypertension, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 10.4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to gather more information about the safety of two treatments, idursulfase-IT and elaprase (both enzyme replacement therapies), for people with Hunter syndrome, a rare genetic disorder affecting development and mental function. Participants will continue receiving the same treatments from previous studies, focusing on those who have shown benefits. It is suited for individuals who have completed certain earlier studies and experienced positive effects from these treatments.

As a Phase 2 and Phase 3 trial, this research measures the treatments' effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancing treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must continue receiving elaprase as you did in the previous studies.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both idursulfase-IT and elaprase have been studied for safety in people with Hunter syndrome. Elaprase is already approved for treating this condition and has known safety information, including the possibility of serious allergic reactions. Studies have demonstrated that it is generally well-tolerated by many patients, though some may experience reactions.

For idursulfase-IT, early research suggests it might help with cognitive issues in Hunter syndrome. A safety study examined patient responses to different doses. The results indicated that while some side effects occurred, the treatment was generally manageable.

Both treatments have undergone thorough testing in previous studies, indicating they are relatively safe for many people, though individual reactions can vary. It is important to discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Idursulfase-IT + Elaprase for Hunter Syndrome because this combination treatment offers a new approach to managing the disease. Unlike current treatments that primarily involve intravenous infusions, Idursulfase-IT is administered directly into the cerebrospinal fluid, potentially allowing it to target the brain more effectively. This method could lead to better outcomes for neurological symptoms, which are a significant challenge in Hunter Syndrome. By potentially improving cognitive function, this treatment approach could offer meaningful benefits that standard therapies haven’t been able to achieve.

What is the effectiveness track record for Idursulfase-IT and Elaprase in treating Hunter syndrome?

Research has shown that idursulfase-IT, which participants in this trial will receive, can help manage symptoms of Hunter syndrome by improving certain physical abilities. Studies indicate it lowers levels of urinary glycosaminoglycans (uGAGs), which accumulate in the body due to the condition. It also improves walking ability and lung function over time. In this trial, idursulfase-IT will be used alongside Elaprase. Together, these treatments aim to further support these improvements and enhance the quality of life for those with Hunter syndrome by addressing both the physical and mental challenges of the condition. ^{2 3 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for children and adults with Hunter syndrome who have cognitive impairment and completed previous studies (HGT-HIT-046 or SHP609-302), showing benefits from idursulfase-IT. They must not be in other clinical trials, have intracranial hypertension, uncontrolled seizures, bleeding disorders, or severe hypertension.

Inclusion Criteria

You have been taking elaprase regularly as part of other studies.

The participant, or participant's legally designated representative, must have been informed of the nature of this open-label extension and must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed. Written consent of the participant's legally designated representative (if applicable) and the participant's consent/assent, as relevant, must be obtained.

You must have finished all the required tests at the end of the previous studies and the doctor must think that you benefited from the medication idursulfase-IT.

Exclusion Criteria

The participant is enrolled in another clinical study, other than studies HGT-HIT-046 or SHP609-302, that involves clinical investigations or use of any investigational product (drug or [intrathecal/spinal] device) within 30 days prior to study enrolment or at any time during the study.

I have high pressure inside my skull.

I have health issues, like uncontrolled seizures or high blood pressure, that make idursulfase-IT unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive idursulfase-IT once monthly and weekly IV infusions of elaprase

Up to approximately 10.4 years

Monthly visits for intrathecal administration, weekly visits for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive treatment as long as benefit is derived or treatment is tolerable

Up to approximately 10.4 years

What Are the Treatments Tested in This Trial?

Interventions

• Elaprase
• Idursulfase-IT

Trial Overview The study extends prior research to further assess the safety of idursulfase-IT and Elaprase treatments in participants with Hunter syndrome and cognitive issues. Participants will continue receiving the same treatment as they did in earlier studies.

How Is the Trial Designed?

Group I: Idursulfase-IT Experimental Treatment 2 Interventions

Participants will receive idursulfase-IT once monthly and weekly IV infusions of elaprase at the dose used in previous studies (HGT-HIT-045/SHP609-302) via IDDD until benefit is no longer derived from the treatment, or treatment is no longer tolerable, or up to approximately 4.8 years.

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?

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

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]

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]

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]

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]

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]

The study identifies a new 1.4-kb transcript that may encode an IDS-like enzyme, which differs from the known Iduronate-2-sulfatase (IDS) by lacking a 207-amino-acid COOH-terminal domain.

This discovery suggests the potential existence of an additional form of the IDS enzyme in humans, which could have important implications for understanding the pathogenesis of Hunter syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an alternative transcript from the human iduronate-2-sulfatase (IDS) gene. Malmgren, H., Carlberg, BM., Pettersson, U., et al.[2006]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1096719225002768

final report of the hunter outcome survey The effectiveness and safety profile of idursulfase support its use for the long-term treatment of patients with MPS II. Introduction.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28974237/

3-year data from the hunter outcome survey (HOS) These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV 1 and hepatosplenomegaly after 1, 2 and 3 years ...

3. elaprase.com elaprase.com/hcp/clinical-trial/

Clinical trial outcomes Safety and efficacy evaluated in a 53-week, randomized, double-blind, placebo-controlled clinical trial of 96 patients with Hunter syndrome, ages 5 to 31 years ...

4. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-017-0712-3

Clinical outcomes in idursulfase-treated patients with ... These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV 1 and hepatosplenomegaly after 1, 2 and 3 years ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02055118

NCT02055118 | Study of Intrathecal Idursulfase-IT ... Study HGT-HIT-094 is a multicenter study designed to determine the effect on clinical parameters of neurodevelopmental status of monthly IT administration ...

6. elaprase.com elaprase.com/hcp/about/safety-information/

ELAPRASE safety results See Important Safety Information including Boxed Warning for lifethreatening anaphylactic reactions, indications, adverse reactions, and immunogenicity.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1096719222003845

Intrathecal idursulfase-IT in patients with neuronopathic ... These data suggest potential benefits of idursulfase-IT in the treatment of cognitive impairment in some patients with neuronopathic MPS II.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00920647

NCT00920647 | A Safety and Dose Ranging Study of ... This Phase I/II study is designed to obtain necessary safety and exposure data, as well as secondary and exploratory outcome measures, to be interpreted and ...