RGX-121-3102 Gene Therapy in Participants With MPS II (Hunter Syndrome)

NCT07236606 | Suspended Phase 3 DMC FDA Drug

• 1 other identifier: RGX-121-3102
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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, efficacy, and pharmacodynamic dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II (Hunter Syndrome)

Conditions

MPS II; Hunter Syndrome (MPS II)

Keywords

Mucopolysaccharidosis II; Gene Therapy

Outcome Measures

Primary Outcomes (3)

• Efficacy of RGX-121 on Neurodevelopmental Function (as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition)

  To evaluate the effect of RGX-121 on the neurodevelopmental function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III).

  Month 24

• Efficacy of RGX-121 on Neurodevelopmental Function (as measured by Kaufman Assessment Battery for Children, 2nd Edition)

  To evaluate the effect of RGX-121 on the neurodevelopmental function as measured by the Kaufman Assessment for Children, 2nd edition (KABC-II). The KABC-II is only given if the participant achieved the max ceiling on the BSID-III Cognitive scale at two consecutive administrations.

  Month 24

• Long-term Safety of RGX-121

  To evaluate the safety of RGX-121 for up to five years including serious and adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0)

  Year 5

Secondary Outcomes (16)

• RGX-121 Change in CSF Biomarkers (as measured by D2S6)

  Week 16, Week 52, Month 24

• RGX-121 Effect on Daily Living Skills

  Month 24

• RGX-121 Change in Brain Volume

  Week 52 and Month 24

• RGX-121 Effect on Auditory Capacity

  Month 24

• RGX-121 Change in Urine Biomarkers (GAGs)

  Week 52 and Month 24

Study Arms (1)

2.9×1011 GC/g brain mass of RGX 121

EXPERIMENTAL

AAV9.CB7.hIDS

Genetic: RGX-121-3102

Interventions

RGX-121-3102 GENETIC

Recombinant adeno-associated virus serotype 9 \[AAV9\] capsid containing human iduronate-2-sulfatase (hIDS) expression cassette

2.9×1011 GC/g brain mass of RGX 121

Eligibility Criteria

• Age: 4 Months - 5 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The participant'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 study-related procedures being performed.
• Is a male ≥ 4 months to \< 5 years of age on Day 1.
• Has a documented diagnosis of MPS II, with a confirmed neuronopathic phenotype.
• Has a BSID-III Cognitive Composite score at or below -1SD (85) from the normative mean.
• Has 2 consecutive neurodevelopment assessments that support a decline on MSEL Visual Reception, Expressive Language, or Fine Motor, or BSID-III Cognitive, Expressive Communication, or Fine Motor of ≥ 1 SD on serial neurodevelopment testing administered between 3 to 36 months apart. Evidence for neurodevelopmental decline can be provided from historical medical records.
• Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS variant(s) as the participant AND the participant, in the opinion of a geneticist, has inherited a neuronopathic form of MPS II. Evidence for support of a relative with neuronopathic MPS II should be provided through medical record documentation of neurodevelopmental function at or below -2 SD from the normative mean. If standard scores are unavailable to document SD from the normative mean, a developmental quotient (AEq/chronological age × 100) of ≤ 60 can be used to document neuronopathic MPS II.
• Has documented variant(s) in IDS known to result in a neuronopathic phenotype. The participant's neuronopathic phenotype will be confirmed by an independent genetic review, with documented supporting evidence from previously reported cases of the same variant(s).
• Has sufficient auditory and visual capacity, with or without aids, to complete the required protocol testing, and be compliant with wearing the aid, if applicable, on testing days.
• Able to ambulate 100 meters independently without use of assistive devices, if the participant is, based on the judgement of the investigator, of a chronological age at screening at which independent ambulation would typically be expected in a child with neuronopathic MPS II.
• Provision of signed and dated informed consent form (ICF) and willingness to comply with all study procedures and availability for the duration of the study.

You may not qualify if:

• Has a contraindication for an intracisternal (IC) and intraventricular (IVR) infusion, including any of the following:
• Review of baseline MRI testing by the team of neuroradiologist/neurosurgeons participating in study shows a contradiction for an IC and IVR infusion.
• History of prior head/neck surgery, which resulted in a contraindication to both IC and IVR infusion, based on review of available information by the team of neuroradiologists/neurosurgeons participating in the study.
• Has any contradiction to computed tomography or general anesthesia.
• Has any contradiction to MRI or gadolinium.
• Has renal insufficiency as determined by an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2, based on creatinine. If the laboratory determines that creatinine is less than the lower limit of assay validation or detection, then the lowest limit cutoff value will be used to estimate eGFR.
• Has previously experienced a clinically significant intracranial bleed that, in the opinion of the investigator and team of neuroradiologists/neurosurgeons, is a contraindication to IC and IVR infusion.
• Has an elevated intracranial pressure (≥ 30 cm H2O).
• Has any neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition that may, in the opinion of the investigator, confound interpretation of study results.
• Has any contraindication to lumbar puncture.
• Has a (cerebral) ventricular shunt that in the opinion of the site neuroradiologist/ neurosurgeon and through discussion with the Medical Monitor, may impact the administration and proper dosing of the participant.
• Has had prior treatment with AAV-based gene therapy product.
• Has undergone HSCT.
• Is receiving idursulfase (ELAPRASE) via IT administration, or a blood brain barrier-crossing ERT. Participants receiving IT ELAPRASE or a blood brain barrier-crossing ERT may enroll if they agree to discontinue these therapies starting at least 3 months prior to dosing with RGX-121, and for the duration of follow-up.
• Has received idursulfase (ELAPRASE) IV and experienced a serious hypersensitivity reaction, including anaphylaxis, deemed related to IV idursulfase (ELAPRASE) administration. If the participant has experienced a severe hypersensitivity reaction, they may enroll in the trial if the hypersensitivity has been treated and the investigator, Medical Monitor, and Sponsor agree that it no longer poses a safety or efficacy risk.

Sponsors & Collaborators

• REGENXBIO Inc.: lead

Study Sites (1)

St. Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Conditions

Sudden Infant Death; Mucopolysaccharidosis II

Condition Hierarchy (Ancestors)

Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Alexander Schramm

  St. Peters University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation

Study Record Dates

• First Submitted: November 5, 2025
• First Posted: November 19, 2025
• Study Start: November 25, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): May 30, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)