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RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome)

Primary Purpose

Mucopolysaccharidosis Type II (MPS II)

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

RGX-121

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis Type II (MPS II) focused on measuring MPS II, gene therapy, Hunter

Eligibility Criteria

5 Years - 17 Years (Child)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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®
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

Sites / Locations

University of California San Francisco, Benioff Children's Hospital
McGill University Heath Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

Biomarkers

Change from baseline in Glycosaminoglycan levels (ng/mL)

Biomarkers

Change from baseline in iduronate-2-sulfatase activity

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)

Change in neurodevelopmental parameters

Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Mullen Scales of Early Learning (MSEL)

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

Full Information

NCT ID

NCT04571970

First Posted

September 23, 2020

Last Updated

February 7, 2023

Sponsor

REGENXBIO Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04571970

Brief Title

RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome)

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)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 11, 2021 (Actual)

Primary Completion Date

May 2023 (Anticipated)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

REGENXBIO Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucopolysaccharidosis Type II (MPS II)

Keywords

MPS II, gene therapy, Hunter

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Single-arm

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single Arm

Arm Type

Experimental

Arm Description

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

Intervention Type

Genetic

Intervention Name(s)

RGX-121

Intervention Description

Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Primary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events and serious adverse events

Description

Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)

Time Frame

24 Weeks

Secondary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events and serious adverse events

Description

Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 5.0)

Time Frame

104 Weeks

Title

Biomarkers

Description

Change from baseline in Glycosaminoglycan levels (ng/mL)

Time Frame

Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104

Title

Biomarkers

Description

Change from baseline in iduronate-2-sulfatase activity

Time Frame

Baseline, Week 1, Week 2, Week 4, Week 12, Week 24, Week 38, Week 52, Week 64, Week 78, Week 104

Title

Change in neurodevelopmental parameters

Description

Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III)

Time Frame

Baseline, Week 52, Week 104

Title

Change in neurodevelopmental parameters

Description

Change from baseline in neurodevelopmental parameters of cognitive function as measured by the Mullen Scales of Early Learning (MSEL)

Time Frame

Baseline, Week 52, Week 104

Title

Change in neurodevelopmental parameters

Description

Change from baseline in neurodevelopmental parameters as measured by the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), Comprehensive Interview Form

Time Frame

Baseline, Week 24, Week 52, Week 78, Week 104

10. Eligibility

Sex

Male

Gender Based

Yes

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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® 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

Facility Information:

Facility Name

University of California San Francisco, Benioff Children's Hospital

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

McGill University Heath Center

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

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RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome)

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