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MPS IIPhase 3NCT07236606

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

A Phase 3 study testing RGX-121-3102 in people with MPS II and Hunter Syndrome (MPS II), run by REGENXBIO Inc. at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 4 months to 5 years, men only
Conditions the study is for
MPS II, Hunter Syndrome (MPS II)
What is being tested?
RGX-121-3102
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
25 Nov 2025to 30 May 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 months to 5 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has received any Investigational Product within 30 days of Day 1 or 5 half-lives before signing of the ICF, whichever is longer.
  • Has any history of lymphoma or history of another cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 1 year before Screening.
  • Has a history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus (HCV) infection, or positive screening tests for hepatitis B surface antigen or hepatitis B core antibody, or hepatitis C (either hepatitis C antibody or HCV RNA) or HIV antibodies.
  • Has a clinically significant ECG abnormality that, in the opinion of the investigator, would compromise the participant's safety.
  • Has a serious or unstable medical or psychological condition that, in the opinion of the investigator, would compromise the participant's safety or successful participation in the study or interpretation of study results.
  • Has uncontrolled seizures that in opinion of the investigator would put the participant at undue risk.
  • Has uncontrolled hypertension despite medical treatment, defined for children ≤ 17 years of age to be systolic blood pressure (SBP) or diastolic blood pressure (DBP) > 99th percentile plus 5mmHg based on normative standards for age, sex, and height.
  • Has a platelet count < 100,000 per µL.
  • Has ALT or AST > 3 × ULN or total bilirubin > 1.5 × ULN at Screening unless the participant has a previously known history of Gilbert's syndrome.
  • Is a first-degree family member of a clinical site employee or of any other individual involved with the conduct of the study.
  • REGENXBIO staff involved in the planning and/or conduct of the study.
  • Employees of the study site or any other individuals involved with the conduct of the study or immediate family members of such individuals.
  • Has any condition that would contraindicate treatment with methylprednisolone, prednisone, tacrolimus, or sirolimus.
  • Has a history of a hypersensitivity reaction to methylprednisolone, tacrolimus, sirolimus, or prednisone.
  • Has a history of a primary immunodeficiency (eg, common variable immunodeficiency syndrome), splenectomy, or any underlying condition that predisposes the participant to infection.
  • Has herpes zoster (varicella zoster virus [VZV]), CMV, or EBV infection that has not completely resolved at least 12 weeks prior to Screening.
  • Has any infection requiring hospitalization or treatment with parenteral anti-infectives not resolved at least 8 weeks prior to Day -2.
  • Has any active infection requiring oral anti-infectives (including antivirals) within 10 days prior to Day -2.
  • Has a history of active tuberculosis (TB) or a positive Quantiferon-TB Gold test during Screening.
  • Has any live, replication-competent vaccine within 6 weeks prior to Day-2.
  • Had major surgery within 8 weeks before signing the ICF or major surgery planned during the study period.
  • Anticipates the need for adenoidectomy or tonsillectomy within 6 months of enrollment. If adenoidectomy or tonsillectomy is anticipated, it should be performed prior to Screening.
  • Has an absolute neutrophil count (ANC) < 1.0 × 103/µL.
  • Has any condition or laboratory abnormality that the investigator believes would not be appropriate for immunosuppressive therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Peter's University Hospital

    New Brunswick, New Jersey, 08901

Other trials in United States

About this study

Official title: A Phase 3, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of RGX 121 in Pediatric Participants With Neuronopathic MPS II (Hunter Syndrome)

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)

Read the detailed description

MPS II (Hunter Syndrome) is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase gene (IDS). Enzyme replacement therapy (ERT) with recombinant idursulfase (ELAPRASE®) is the only approved product for the treatment of Hunter syndrome; however, ERT as currently administered does not cross the blood brain barrier and is therefore unable to address the unmet need in MPS II patients with central nervous system (CNS) (neurodevelopment and behavior) involvement. RGX-121 is designed to deliver a functional gene to cells in the CNS. Iduronate-2-sulfatase (I2S) may then be secreted by transduced cells, which may then cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase III, open-label, confirmatory study investigating the efficacy, safety, and pharmacodynamics of RGX-121 treatment of patients with neuronopathic mucopolysaccharidosis type II (MPS II) aged ≥ 4 months to less than 5 years. A one time dose of RGX-121 will be studied in 2 male pediatric participants with neuronopathic MPS II, as supplemented in the analysis with 13 participants who were separately analyzed in the pivotal RGX-121-101 Part 2 study.

Being tested
RGX-121-3102
Keywords
Mucopolysaccharidosis II, Gene Therapy
Medical subject headings
Sudden Infant Death, Mucopolysaccharidosis II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RGX-121-3102Genetic

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

Study groups in NCT07236606
Study groupRoleWhat they receive
2.9×1011 GC/g brain mass of RGX 121ExperimentalAAV9.CB7.hIDS
Receives: Genetic: RGX-121-3102

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Month 24

  2. 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.

    Measured: Month 24

  3. 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)

    Measured: Year 5

Secondary outcomes (16)

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

    To assess the effect of RGX-121 on Glycosaminoglycan (GAG) levels in CSF as measured by D2S6.

    Measured: Week 16, Week 52, Month 24

  2. RGX-121 Effect on Daily Living Skills

    Change from baseline on daily living skills as measured by the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), Comprehensive Interview Form. The Vineland Adaptive Behavior Scale II (VABS-II) is a standardized paediatric functional assessment tool. The VABS-II offers a way to measure personal and social self-sufficiency in real-life situations and to observe how these cognitive abilities impact the autonomy management process when put into practice. The VABS-II consists in a semi-structured interview with the parents. Higher scores mean a better outcome.

    Measured: Month 24

  3. RGX-121 Change in Brain Volume

    To evaluate the efficacy of RGX-121 on the participant's change in brain volume of gray and white matter.

    Measured: Week 52 and Month 24

  4. RGX-121 Effect on Auditory Capacity

    To assess the effect of RGX-121 on change in auditory capacity measured by ABR testing from baseline.

    Measured: Month 24

  5. RGX-121 Change in Urine Biomarkers (GAGs)

    To assess the effect of RGX-121 on ERT-naïve, ERT- continuing participants and ERT-withdrawn participants GAGs levels in urine.

    Measured: Week 52 and Month 24

  6. RGX-121 Safety

    To evaluate the safety of RGX-121 for up to two years including adverse event reporting, laboratory evaluations, vital signs, physical examinations, and neurological assessments.

    Measured: Month 24

  7. RGX-121 Change in CSF Biomarkers (I2S)

    To assess the effect of RGX-121 on I2S in cerebral spinal fluid (CSF)

    Measured: Week 52 and Month 24

  8. RGX-121 Change in Plasma Biomarkers (GAGs)

    To asses the effect of RGX-121 on GAGs levels in plasma.

    Measured: Week 52 and Month 24

  9. RGX-121 Change in Plasma Biomarkers (I2S)

    To assess the effect of RGX-121 on I2S levels in plasma.

    Measured: Week 52 and Month 24

  10. RGX-121 Long-term Change in Neurodevelopmental Parameters

    Change from baseline in neurodevelopment parameters of cognitive, behavioral and adaptive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or Kaufman Assessment Battery for Children, 2nd Edition (KABC-II).

    Measured: Year 5

  11. RGX-121 Long-term Change in CSF Biomarkers (D2S6)

    To assess the long-term effect of RGX-121 on GAG levels in CSF as measured by D2S6.

    Measured: Year 5

  12. RGX-121 Long-term Change in CSF Biomarkers (I2S)

    To assess the long-term effect of RGX-121 on I2S levels in CSF.

    Measured: Year 5

  13. RGX-121 Long-term Change in Plasma Biomarkers (GAGs)

    To assess the long-term effect of RGX-121 on GAGs levels in plasma.

    Measured: Year 5

  14. RGX-121 Long-term Change in Plasma Biomarkers (I2S)

    To assess the long-term effect of RGX-121 on I2S levels in Plasma.

    Measured: Year 5

  15. RGX-121 Long-term Effect on Auditory Capacity

    To assess the long-term effect of RGX-121 on change in auditory capacity measured by ABR testing from baseline to Year 5.

    Measured: Year 5

  16. RGX-121 Long-term Effect on Urine Biomarkers

    To assess the long-term effect of RGX-121 on ERT-naïve, ERT- continuing participants and ERT-withdrawn participants GAGs levels in urine.

    Measured: Year 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2025
  2. Study start25 Nov 2025
  3. Primary completion30 Apr 2028 (estimated)
  4. Study completion30 May 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Dose Escalation
Masking
None (open label)
Enrolment
2 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07236606
Sponsor's protocol ID
RGX-121-3102
Status last verified
Jun 2026
First submitted
5 Nov 2025
Last updated
4 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RGX-121-3102 in people with MPS II and Hunter Syndrome (MPS II), run by REGENXBIO Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of RGX-121 on Neurodevelopmental Function (as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition) (time frame: Month 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07236606.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.

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