Mucopolysaccharidosis Type II (MPS II)Phase 1/2NCT04571970
RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome)
A Phase 1/2 study testing RGX-121 in people with Mucopolysaccharidosis Type II (MPS II), run by REGENXBIO Inc. at 2 sites in 2 countries.
Trial summary
RGX-121 is a gene therapy which is designed to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. 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 severe MPS II. Read more about this study
- Who is it for?
- Ages 5 to 17 years, men only
- Conditions the study is for
- Mucopolysaccharidosis Type II (MPS II)
- What is being tested?
- RGX-121
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 11 Mar 2021to 23 May 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 5 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Meets any of the following criteria:
- 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), OR
- 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), OR
- Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the participant AND the participant in the opinion of a geneticist has inherited a neuronopathic form of MPS II, OR
- Has documented mutation(s) in IDS that in the opinion of a geneticist is known to result in a neuronopathic phenotype AND in the opinion of a clinician has a neuronopathic form of MPS II
Who cannot join
- Has contraindications for intracisternal injection, intracerebroventricular injection, or lumbar puncture
- Has contraindications for immunosuppressive therapy
- Has any neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
- Has had prior treatment with an AAV-based gene therapy product
- If receiving ELAPRASE® via intrathecal (IT) administration, must agree to discontinue IT idursulfase for the duration of the study
- Has experienced a serious hypersensitivity reaction to intravenous (IV) ELAPRASE®
Show all 9Show fewer
- Is currently failing to respond to idursulfase (ELAPRASE®) IV due to neutralizing anti-idursulfase antibodies
- Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing of the ICF, whichever is longer
- Has a platelet count <100,000 per microliter (µL), absolute neutrophil count <1.0 × 103/µL, or aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN at screening unless the participant has a previously known history of Gilbert's syndrome
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of California San Francisco, Benioff Children's Hospital
Oakland, California, 94609
About this study
Official title: A Phase I/II Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of RGX-121 in Children 5 Years of Age and Older With MPS II (Hunter Syndrome)
RGX-121 is a gene therapy which is designed to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. 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 severe MPS II.
Read the detailed description
MPS II is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. 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 CNS (neurocognition and behavior) involvement. RGX-121 is designed to deliver a healthy gene to cells in the CNS and iduronate-2-sulfatase (I2S) may then be secreted by transduced cells which may cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase I/II, multicenter, open-label, single arm study of RGX-121. Approximately 6 children (≥ 5 years to < 18 years of age) who have severe (neuronopathic) MPS II could be enrolled into a single dose cohort and will receive a single dose of RGX-121 administered by IC or ICV injection. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period). Following completion of the primary study period, participants will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-121.
- Conditions
- Mucopolysaccharidosis Type II (MPS II)
- Being tested
- RGX-121
- Keywords
- MPS II, gene therapy, Hunter
- Medical subject headings
- Mucopolysaccharidosis II, Sudden Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RGX-121Genetic
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | 6.5 × 10^10 GC/g brain mass of RGX-121 Receives: Genetic: RGX-121 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events and serious adverse events
Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)
Measured: 24 Weeks
Secondary outcomes (6)
Number of participants with treatment-related adverse events and serious adverse events
Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)
Measured: 104 Weeks
Biomarkers
Change from baseline in Glycosaminoglycan levels (ng/mL)
Measured: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Biomarkers
Change from baseline in iduronate-2-sulfatase activity
Measured: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Change in neurodevelopmental parameters
Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III)
Measured: Baseline, Week 52, Week 104
Change in neurodevelopmental parameters
Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Mullen Scales of Early Learning (MSEL)
Measured: Baseline, Week 52, Week 104
Change in neurodevelopmental parameters
Change from baseline in neurodevelopmental parameters as measured by the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), Comprehensive Interview Form
Measured: Baseline, Week 24, Week 52, Week 78, Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start11 Mar 2021
- Primary completion9 May 2023
- Study completion23 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis Type II (MPS II)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- REGENXBIO Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04571970
- Sponsor's protocol ID
- RGX-121-1102
- Status last verified
- Jan 2025
- First submitted
- 23 Sep 2020
- Last updated
- 28 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of RGX-121 in Children 5 Years of Age and Older With MPS II (Hunter Syndrome)
- ClinicalTrials.gov ID
- NCT04571970
- Acronym / sponsor ID
- RGX-121-1102
- Conditions
- Mucopolysaccharidosis Type II (MPS II)
- Keywords
- MPS II, gene therapy, Hunter
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- REGENXBIO Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Mar 2021 (actual)
- Primary completion
- 9 May 2023 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 1 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RGX-121 is a gene therapy which is designed to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. 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 severe MPS II.
Detailed description
MPS II is a rare X-linked recessive genetic disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. 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 CNS (neurocognition and behavior) involvement. RGX-121 is designed to deliver a healthy gene to cells in the CNS and iduronate-2-sulfatase (I2S) may then be secreted by transduced cells which may cross-correct non-transduced cells by taking up the functional enzyme. This is a Phase I/II, multicenter, open-label, single arm study of RGX-121. Approximately 6 children (≥ 5 years to < 18 years of age) who have severe (neuronopathic) MPS II could be enrolled into a single dose cohort and will receive a single dose of RGX-121 administered by IC or ICV injection. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period). Following completion of the primary study period, participants will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-121.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Genetic: RGX-1216.5 × 10^10 GC/g brain mass of RGX-121 |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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), OR
- 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), OR
- Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the participant AND the participant in the opinion of a geneticist has inherited a neuronopathic form of MPS II, OR
- Has documented mutation(s) in IDS that in the opinion of a geneticist is known to result in a neuronopathic phenotype AND in the opinion of a clinician has a neuronopathic form of MPS II
Key exclusion criteria (9 listed)
- Has contraindications for intracisternal injection, intracerebroventricular injection, or lumbar puncture
- Has contraindications for immunosuppressive therapy
- Has any neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
- Has had prior treatment with an AAV-based gene therapy product
- If receiving ELAPRASE® via intrathecal (IT) administration, must agree to discontinue IT idursulfase for the duration of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RGX-121Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette | Genetic | Single Arm |
Primary outcome
Number of participants with treatment-related adverse events and serious adverse events
Time frame: 24 Weeks
Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)
6 secondary outcomes
Number of participants with treatment-related adverse events and serious adverse events
Time frame: 104 Weeks
Biomarkers
Time frame: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Biomarkers
Time frame: Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104
Change in neurodevelopmental parameters
Time frame: Baseline, Week 52, Week 104
Change in neurodevelopmental parameters
Time frame: Baseline, Week 52, Week 104
Change in neurodevelopmental parameters
Time frame: Baseline, Week 24, Week 52, Week 78, Week 104
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RGX-121 in people with Mucopolysaccharidosis Type II (MPS II), run by REGENXBIO Inc. at 2 sites in 2 countries.
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 5 inclusion and 9 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: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of participants with treatment-related adverse events and serious adverse events (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jan 2025.