RGX-121 Gene Therapy for Hunter Syndrome

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new gene therapy called RGX-121 for children with Hunter Syndrome, also known as MPS II. The goal is to determine the safety and effectiveness of delivering a healthy gene to the brain. Researchers will test different doses to identify the most effective one. Boys diagnosed with a severe form of MPS II who face daily challenges due to the condition might be suitable candidates for this trial. As a Phase 2 and Phase 3 trial, this research measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering hope for an effective treatment.

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.

Is there any evidence suggesting that RGX-121 is likely to be safe for humans?

Research has shown that RGX-121, a gene therapy for Hunter Syndrome, has been promising in earlier studies. Patients in these studies generally handled the treatment well. Specifically, one study demonstrated that RGX-121 improved patient outcomes over a year, suggesting the treatment is safe for those with Hunter Syndrome.

While the FDA is still reviewing the therapy, the data so far has revealed no major safety issues. The therapy involves a single injection into the brain area, a common and safely managed method for such treatments.

In summary, current research indicates that RGX-121 is generally safe and well-tolerated, making it a potential option for patients with Hunter Syndrome. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Hunter Syndrome?

Unlike the standard treatments for Hunter Syndrome, which typically involve enzyme replacement therapy, RGX-121 offers a novel approach through gene therapy. Researchers are excited because RGX-121 directly targets the root genetic cause of the condition by delivering a functional copy of the IDS gene. This method has the potential to provide long-lasting benefits with a single administration, possibly reducing the need for frequent treatments. The hope is that this treatment will not only alleviate symptoms more effectively but also improve overall brain function and quality of life for patients.

What evidence suggests that RGX-121 might be an effective treatment for Hunter Syndrome?

Research has shown that RGX-121, a gene therapy, could help treat Hunter Syndrome (MPS II). In studies, a single treatment with RGX-121 improved patient outcomes by delivering a working version of the missing gene to the central nervous system. This method aims to prevent the brain and bone problems linked to the condition. Data from twelve months of research showed positive results, indicating that RGX-121 can help manage MPS II symptoms. The therapy is designed to be safe and well-tolerated, making it a promising treatment option. Participants in this trial will receive different doses of RGX-121 to evaluate its effectiveness and safety across various dosages. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. ir.regenxbio.com ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-twelve-month-pivotal-data-phase

REGENXBIO Presents Positive Twelve-Month Pivotal Data ... 12-month pivotal data further demonstrate the ability of one-time RGX-121 treatment to improve outcomes for patients with MPS II.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03566043

NCT03566043 | CAMPSIITE™ RGX-121 Gene Therapy in ... 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. Detailed ...

3. prnewswire.com prnewswire.com/news-releases/regenxbio-presents-positive-twelve-month-pivotal-data-from-phase-iiiiii-campsiite-trial-of-rgx-121-for-treatment-of-mps-ii-302547381.html

REGENXBIO Presents Positive Twelve-Month Pivotal Data ... 12-month pivotal data further demonstrate the ability of one-time RGX-121 treatment to improve outcomes for patients with MPS II.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10875268/

Comparative dose effectiveness of intravenous and intrathecal ... AAV.CB7.hIDS (RGX-121) prevented neurologic and skeletal manifestations of murine mucopolysaccharidosis type II after either intravenous or intrathecal ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04571970?cond=hunters%20syndrome&checkSpell=&rank=8

RGX-121 Gene Therapy in Children 5 Years of Age and ... This study is a phase I/II study to determine whether RGX-121 is safe, well tolerated, and potentially effective in children five years of age and over who have ...

6. regenxbio.gcs-web.com regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-fda-review-extension-bla-rgx-121-treat

REGENXBIO Announces FDA Review Extension of BLA for ... RGX-121 would be the first and only potential one-time commercially-available therapy designed to directly address the underlying genetic cause ...

7. empr.com empr.com/news/gene-therapy-for-hunter-syndrome-under-fda-review/

Gene Therapy for Hunter Syndrome Under FDA Review The FDA has accepted for Priority Review the BLA for RGX-121 for the treatment of mucopolysaccharidosis II, also known as Hunter syndrome.

8. neurology.org neurology.org/doi/10.1212/WNL.96.15_supplement.4164

RGX-121 gene therapy for severe Mucopolysaccharidosis ... RGX-121 is administered as a one-time injection into the cisterna magna or lateral cerebral ventricle of participants with severe MPS II ages 4 months to 5 ...