What side effects are associated with this type of intervention?

Enzyme-replacement therapies (ERTs) for Hunter Syndrome, such as idursulfase and the investigational tividenofusp alfa, are generally well-tolerated but can have side effects. Common side effects include infusion-related reactions like fever, headache, rash, and hypertension. Some patients may experience more severe reactions such as anaphylaxis. Long-term use of ERTs can also lead to the development of antibodies against the enzyme, potentially reducing treatment efficacy.

What prior FDA approvals exist?

Hunter Syndrome (Mucopolysaccharidosis type II) is primarily treated with enzyme-replacement therapies (ERT). The FDA has approved Idursulfase (Elaprase) for this purpose. Idursulfase is designed to replace the deficient enzyme in patients with MPS II, helping to reduce the accumulation of glycosaminoglycans. Tividenofusp alfa, currently under investigation, is a CNS-penetrant ERT, which aims to address both central nervous system and somatic symptoms of the disease.

What other types of research exist?

As of now, there are no specific novel alternatives to Tividenofusp alfa mentioned in the provided context. However, patients and healthcare providers should look for other CNS-penetrant enzyme-replacement therapies or gene therapies that are in clinical trials or have recently been approved for lysosomal storage disorders, as these may offer new treatment options for Hunter Syndrome in the near future.

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Enzyme-replacement Therapy

Tividenofusp Alfa for Hunter Syndrome (COMPASS Trial)

Q: What is the mechanism of action of this treatment?

Hunter Syndrome treatments primarily involve enzyme replacement therapies (ERTs) like idursulfase, which supplement the deficient enzyme to reduce glycosaminoglycan (GAG) accumulation in tissues. Tividenofusp alfa, a CNS-penetrant ERT, is under investigation for its ability to cross the blood-brain barrier and address neurological symptoms, a critical advancement since traditional ERTs do not effectively treat CNS manifestations. This matters greatly for patients with neuronopathic Hunter Syndrome, as it offers hope for mitigating cognitive decline alongside peripheral symptom management.

Phase 2 & 3

Recruiting

Research Sponsored by Denali Therapeutics Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)

Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <17 years (Cohort B)

Must not have

Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy

Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment called tividenofusp alfa for patients with a rare genetic disorder called MPS II. The treatment aims to replace missing enzymes to help break down harmful substances in the brain and body.

Who is the study for?

This trial is for kids with Hunter Syndrome (MPS II), aged 2-6 or 6-17, depending on the group. They must have been treated with idursulfase for at least 4 months. Kids can't join if they've had gene or stem cell therapy for MPS, are unable to undergo lumbar punctures/MRIs, received CNS-targeted ERT recently, or participated in other drug trials within the last 60 days.

What is being tested?

The study compares Tividenofusp Alfa (DNL310), a new treatment that reaches the brain better than current therapies, against Idursulfase, which is standard care. It's randomized and double-blind meaning neither participants nor researchers know who gets which treatment until after results are collected.

What are the potential side effects?

Potential side effects aren't specified here but may include reactions similar to those seen with enzyme replacement therapies such as allergic reactions, pain at injection site, headache, fever and chills.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with MPS II.

Select...

I am between 2 and 17 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have had gene or stem cell therapy for my condition.

Select...

I have a genetic mutation that explains my developmental delay.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Open-label Treatment PhaseExperimental Treatment2 Interventions

Participants who meet pre-specified criteria may receive DNL310 or idursulfase

Group II: Cohort B: Participants with nnMPS IIExperimental Treatment2 Interventions

Group III: Cohort A: Participants with nMPS IIExperimental Treatment2 Interventions

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Hunter Syndrome treatments primarily involve enzyme replacement therapies (ERTs) like idursulfase, which supplement the deficient enzyme to reduce glycosaminoglycan (GAG) accumulation in tissues. Tividenofusp alfa, a CNS-penetrant ERT, is under investigation for its ability to cross the blood-brain barrier and address neurological symptoms, a critical advancement since traditional ERTs do not effectively treat CNS manifestations. This matters greatly for patients with neuronopathic Hunter Syndrome, as it offers hope for mitigating cognitive decline alongside peripheral symptom management.

Further experience with the use of 6-thioguanine in patients with Crohn's disease.A PRISMA-compliant systematic review and network meta-analysis on the efficacy between different regimens based on Tripterygium wilfordii Hook F in patients with primary nephrotic syndrome.Enzyme replacement therapy for mucopolysaccharidosis VI--experience in Taiwan.