RGX-121 Gene Therapy for Hunter Syndrome

Recruiting at 5 trial locations

Overseen By Patient Advocacy

Age: < 18

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: REGENXBIO, Inc.

Must not be taking: Idursulfase, Blood brain barrier-crossing ERT

Disqualifiers: Neuropsychiatric condition, Ventricular shunt, 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

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are receiving idursulfase (ELAPRASE®) via intrathecal administration or a blood brain barrier-crossing enzyme replacement therapy, you will need to stop these treatments at least 3 months before starting the trial and for the 24 months of follow-up.

What data supports the effectiveness of the RGX-121 treatment for Hunter Syndrome?

Gene therapy, like RGX-121, has shown promise in treating genetic conditions by replacing faulty genes with functional ones. For example, retinal gene therapy has improved vision in patients with choroideremia, a genetic eye disorder, suggesting that similar approaches could be effective for other genetic diseases. ^{1 2 3 4 5}

Is RGX-121 gene therapy generally safe for humans?

The safety of a similar gene therapy using an adeno-associated virus (AAV8) vector was tested in humans for a different condition, showing it was generally well tolerated with some mild inflammation that resolved with treatment. This suggests that the approach may be safe, but specific data for RGX-121 in humans is not provided. ^{6 7 8 9 10}

What is the purpose of this trial?

RGX-121 is a gene therapy which is intended to deliver a functional copy of the iduronate-2-sulfatase gene (IDS) to the central nervous system. This study is a safety and efficacy, dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II.

Eligibility Criteria

This trial is for boys aged 4 months to under 5 years with Hunter Syndrome, specifically those with severe forms or declining neurocognitive function. Participants must have a legal guardian's consent and cannot have had certain treatments like stem cell transplants, recent investigational products, or specific gene therapies.

Inclusion Criteria

I am a boy between 4 months and 5 years old.

I have MPS II with severe symptoms or a decline in brain function tests.

The subject's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures

Exclusion Criteria

I have a shunt in my brain that could affect medication dosing.

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

Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Phase I/II dose escalation study of RGX-121 with three one-time doses in up to 16 pediatric subjects

24 weeks

Multiple visits for dose administration and monitoring

Follow-up Part 1

Participants are monitored for safety and efficacy after treatment in Part 1

80 weeks

Treatment Part 2

Pivotal expansion study with a single dose of RGX-121 in up to 30 pediatric patients

24 months

Various timepoints for assessment

Follow-up Part 2

Participants are monitored for safety and efficacy after treatment in Part 2

24 months

Long-term follow-up

Participants may enroll in a separate 3-year long-term follow-up study for safety monitoring

3 years

Treatment Details

Interventions

• RGX-121

Trial Overview The trial tests RGX-121 gene therapy designed to deliver a functional IDS gene to the central nervous system. It aims to determine the safety, effectiveness, and tolerability of varying doses in young male patients with MPS II.

Participant Groups

Group I: Part 2: RGX-121 Pivotal Expansion Experimental Treatment 1 Intervention

2.9x10\^11 GC/g brain mass of RGX-121 (transgene-specific PCR assay)

Group II: Part 1: RGX-121 Dose 3 Expanded Cohort Experimental Treatment 1 Intervention

2.9x10\^11 GC/g brain mass of RGX-121 (transgene-specific PCR assay) equivalent to, 2.0x10\^11 GC/g brain mass of RGX-121 (Poly-A-specific PCR assay)

Group III: Part 1: RGX-121 Dose 3 Experimental Treatment 1 Intervention

2.0x10\^11 GC/g brain mass of RGX-121

Group IV: Part 1: RGX-121 Dose 2 Expanded Cohort Experimental Treatment 1 Intervention

6.5x10\^10 GC/g brain mass of RGX-121

Group V: Part 1: RGX-121 Dose 2 Experimental Treatment 1 Intervention

6.5x10\^10 GC/g brain mass of RGX-121

Group VI: Part 1: RGX-121 Dose 1 Experimental Treatment 1 Intervention

1.3x10\^10 GC/g brain mass of RGX-121

Who Is Running the Clinical Trial?

REGENXBIO, Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

Regenxbio Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

REGENXBIO Inc.

Lead Sponsor

Trials

25

Recruited

3,100+

Findings from Research

The AAV8-RS1 gene therapy was generally well tolerated in a phase I/IIa trial involving nine participants with X-linked retinoschisis, with only one individual experiencing significant adverse effects, which were manageable with corticosteroids.

Some participants showed transient closure of retinal cavities, suggesting potential efficacy, but further studies with additional doses and immunosuppressive treatments are needed to fully assess safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery. Cukras, C., Wiley, HE., Jeffrey, BG., et al.[2022]

The gene therapy rAAV2tYF-CB-hRS1 was found to be generally safe for treating X-linked retinoschisis in a study involving 27 participants (22 adults and 5 children), with no serious adverse events leading to early termination, although some mild to moderate ocular inflammation was observed.

Despite its safety, the treatment did not show significant improvements in visual acuity or other measures of eye function compared to the untreated eye, indicating that while the therapy is well tolerated, it may not be effective in producing measurable benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Delivery of rAAV2tYF-CB-hRS1 Vector for Gene Augmentation Therapy in Patients with X-Linked Retinoschisis: 1-Year Clinical Results. Pennesi, ME., Yang, P., Birch, DG., et al.[2023]

References

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

Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Gene therapy for inherited retinal diseases. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Detailed clinical characterisation, unique features and natural history of autosomal recessive RDH12-associated retinal degeneration. [2020]

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

Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. [2023]

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

AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models. [2022]

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

Preclinical safety evaluation of a recombinant AAV8 vector for X-linked retinoschisis after intravitreal administration in rabbits. [2021]

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

Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery. [2022]

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

Intravitreal Delivery of rAAV2tYF-CB-hRS1 Vector for Gene Augmentation Therapy in Patients with X-Linked Retinoschisis: 1-Year Clinical Results. [2023]

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

Report from a Workshop on Accelerating the Development of Treatments for Inherited Retinal Dystrophies Associated with Mutations in the RDH12 Gene. [2022]

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

Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal Structure and Function. [2019]