Idursulfase-IT + Elaprase for Hunter Syndrome

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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is an extension of two previous studies (HGT-HIT-046 \[NCT01506141\] and SHP609-302 \[NCT02412787\]). Participants must have completed one of the previous studies. The main aim of this study is to collect more information about the safety of the treatments, idursulfase-IT and elaprase, in children and adults with Hunter syndrome and cognitive impairment. Participants will receive the same treatment as in the previous studies.

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.

What data supports the effectiveness of the drug Idursulfase-IT + Elaprase for Hunter Syndrome?

Research shows that Elaprase (idursulfase) is effective in treating Hunter syndrome by increasing walking distance, improving lung function, and reducing organ size and harmful substances in the body. It is generally well tolerated, although some infusion reactions can occur. ^{1 2 3 4 5}

Is Idursulfase-IT + Elaprase safe for humans?

Idursulfase and its formulations, including Idursulfase-IT, are generally well tolerated in humans, though some people may experience mild infusion reactions. In long-term studies, serious adverse events were not linked to the treatment, and no deaths or treatment discontinuations due to adverse events were reported. ^{1 3 6 7 8}

How is the drug Idursulfase-IT + Elaprase unique for treating Hunter syndrome?

Idursulfase-IT + Elaprase is unique because it combines enzyme replacement therapy with a specific enzyme, iduronate-2-sulfatase, to address the enzyme deficiency in Hunter syndrome, improving symptoms like walking distance and lung function. This drug is the first successful symptomatic therapy for this condition, directly targeting the root cause by replacing the missing enzyme. ^{1 2 4 8 9}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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 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]

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-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]

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]

References

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

Idursulfase in Hunter syndrome treatment. [2017]

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

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

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

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

5. 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]

6. 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]

7. 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]

8. 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]

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

Identification of an alternative transcript from the human iduronate-2-sulfatase (IDS) gene. [2006]