What side effects are associated with this type of intervention?

Gene therapy for Hunter Syndrome, such as RGX-121, aims to deliver a functional copy of the IDS gene to the central nervous system. Known side effects from similar gene therapy trials include expected adverse events that do not cause long-term disability. These may include mild to moderate reactions at the injection site, transient immune responses, and other manageable symptoms. Overall, gene therapy appears to be well-tolerated with no severe long-term adverse effects reported.

What prior FDA approvals exist?

Hunter Syndrome, also known as Mucopolysaccharidosis II (MPS II), has seen FDA approval for enzyme replacement therapies (ERT) such as idursulfase (Elaprase), which provides the deficient enzyme iduronate-2-sulfatase. However, gene therapy approaches like RGX-121, which aim to deliver a functional IDS gene directly to the central nervous system, represent a novel and promising area of research. These gene therapies are still under investigation and have not yet received FDA approval.

What other types of research exist?

Promising alternatives to RGX-121 for Hunter Syndrome patients include enzyme replacement therapies like idursulfase (Elaprase) and investigational treatments such as hematopoietic stem cell transplantation (HSCT) with gene editing techniques. Additionally, substrate reduction therapies and other gene therapies targeting the IDS gene or related pathways are being explored in clinical trials.

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Gene Therapy

RGX-121 Gene Therapy for Hunter Syndrome

Phase 1 & 2

Waitlist Available

Research Sponsored by REGENXBIO, Inc.

Eligibility Criteria Checklist

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

Must have

Has a documented diagnosis of MPS II AND a neurocognitive testing score ≤ 1 ½ standard deviation (SD) from the test normative mean (BSID-III: 77 and MSEL Visual Reception: 35)

Has a documented diagnosis of MPS II AND has a decline of ≥ 1 standard deviation on serial neurocognitive testing administered between 3 to 36 months apart (BSID-III Cognitive or MSEL Visual Reception)

Must not have

Has contraindications for immunosuppressive therapy

Is currently failing to respond to idursulfase (ELAPRASE®) IV due to neutralizing anti-idursulfase antibodies

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 1, week 2, week 4, week 12, week 24, week 38, week 52, week 64, week 78, week 104

Awards & highlights

No Placebo-Only Group

Summary

This trial tests RGX-121, a gene therapy designed to help children with severe MPS II by delivering a healthy gene to their brain cells. The goal is to produce an enzyme that can improve brain function. The study will check if this treatment is safe and effective. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients.

Who is the study for?

This trial is for children over 5 with severe Hunter Syndrome, showing specific neurocognitive decline. They must have a genetic diagnosis of MPS II and not be responding to standard treatments. Kids can't join if they've had gene therapy before, are allergic to certain enzyme treatments, or have immune system issues that prevent them from taking immunosuppressants.

What is being tested?

The study tests RGX-121 gene therapy aimed at delivering a working IDS gene to the brain. It's in early stages (phase I/II) to see if it's safe and might work for kids with neuronopathic Hunter Syndrome who haven't improved on current therapies.

What are the potential side effects?

Specific side effects aren't listed here, but common risks of gene therapies include immune reactions, potential damage at injection site, and general symptoms like fever or fatigue. Long-term effects are unknown due to the novelty of this treatment.

Eligibility Criteria

Inclusion Criteria

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

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I have MPS II and my neurocognitive test scores are below average.

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I have MPS II and my brain function tests show a decline over time.

Exclusion Criteria

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

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I cannot take immunosuppressive medications due to health reasons.

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My body is not responding to ELAPRASE® due to certain antibodies.

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I agree to stop my ELAPRASE® treatment via spinal injection for the study.

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I have previously received AAV-based gene therapy.

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I cannot have treatments injected into my spine or brain.

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I have a brain function issue not caused by my MPS II condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 1, week 2, week 4, week 12, week 24, week 38, week 52, week 64, week 78, week 104

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 1, week 2, week 4, week 12, week 24, week 38, week 52, week 64, week 78, week 104

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 1, week 2, week 4, week 12, week 24, week 38, week 52, week 64, week 78, week 104 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Biomarkers

Change in neurodevelopmental parameters

Number of participants with treatment-related adverse events and serious adverse events

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single ArmExperimental Treatment1 Intervention

6.5 × 10\^10 GC/g brain mass of RGX-121

0 / 8Eligibility 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 focus on replacing or supplementing the deficient enzyme iduronate-2-sulfatase (IDS). Enzyme replacement therapy (ERT) provides synthetic IDS to reduce glycosaminoglycan (GAG) accumulation but is less effective for neurological symptoms due to its inability to cross the blood-brain barrier. Gene therapy, like RGX-121, delivers a functional IDS gene directly to the CNS, potentially addressing both systemic and neurological symptoms by enabling endogenous enzyme production in critical areas, including the brain.

Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques.Insights gained from gene therapy in animal models of retGC1 deficiency.