CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome)

NCT03566043 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RGX-121-101
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 5

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 and efficacy, dose ranging study to determine whether RGX-121 is safe, effective and well-tolerated by patients with MPS II.

Conditions

Mucopolysaccharidosis Type II (MPS II)

Keywords

MPS II; gene therapy; Hunter Syndrome; Lysosomal Storage Disorder

Outcome Measures

Primary Outcomes (5)

• Part 1 Safety

  Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 4.03).

  24 Weeks

• Part 2 Biomarkers

  CSF GAG levels (as measured by D2S6)

  52 Weeks

• Part 2 Biomarkers

  CSF GAG levels (as measured by D2S6)

  104 weeks

• Part 2 Neurodevelopmental parameters

  Neurodevelopmental function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or Mullen Scales of Early Learning (MSEL). The Bayley Scales of Infant Development, or the BSID-III is an individually administered test, designed to evaluate the developmental functioning of infants and small children, between 1 and 42 months of age. The purpose of the test is to identify infants and children with developmental delay. The Mullen Scales of Early Learning (MSEL) is a developmental test to measure cognitive ability, language and motor development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. An increase in raw and age equivalent scores indicates neurodevelopmental skill acquisition. Standard scores compare function to age matched normative data.

  52 Weeks

• Part 2 Neurodevelopmental parameters

  Neurodevelopmental function as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or Mullen Scales of Early Learning (MSEL). The Bayley Scales of Infant Development, or the BSID-III is an individually administered test, designed to evaluate the developmental functioning of infants and small children, between 1 and 42 months of age. The purpose of the test is to identify infants and children with developmental delay. The Mullen Scales of Early Learning (MSEL) is a developmental test to measure cognitive ability language and motor development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. An increase in raw and age equivalent scores indicates neurodevelopmental skill acquisition. Standard scores compare function to age matched normative data.

  104 weeks

Secondary Outcomes (8)

• Part 1 Safety

  104 Weeks

• Part 1 Biomarkers

  104 Weeks

• Part 1 Neurodevelopmental parameters

  104 Weeks

• Part 1 Change in neurodevelopmental parameters

  104 Weeks

• Part 2 Change in neurodevelopmental parameters

  52 Weeks

Study Arms (6)

Part 1: RGX-121 Dose 1

EXPERIMENTAL

1.3x10\^10 GC/g brain mass of RGX-121

Genetic: RGX-121

Part 1: RGX-121 Dose 2

EXPERIMENTAL

6.5x10\^10 GC/g brain mass of RGX-121

Genetic: RGX-121

Part 1: RGX-121 Dose 2 Expanded Cohort

EXPERIMENTAL

6.5x10\^10 GC/g brain mass of RGX-121

Genetic: RGX-121

Part 1: RGX-121 Dose 3

EXPERIMENTAL

2.0x10\^11 GC/g brain mass of RGX-121

Genetic: RGX-121

Part 1: RGX-121 Dose 3 Expanded Cohort

EXPERIMENTAL

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)

Genetic: RGX-121

Part 2: RGX-121 Pivotal Expansion

EXPERIMENTAL

2.9x10\^11 GC/g brain mass of RGX-121 (transgene-specific PCR assay)

Genetic: RGX-121

Interventions

RGX-121 GENETIC

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

Part 1: RGX-121 Dose 1; Part 1: RGX-121 Dose 2; Part 1: RGX-121 Dose 2 Expanded Cohort; Part 1: RGX-121 Dose 3; Part 1: RGX-121 Dose 3 Expanded Cohort; Part 2: RGX-121 Pivotal Expansion

Eligibility Criteria

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

You may qualify if:

• 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
• Is a male ≥4 months to \< 5 years of age on Day 1
• Must meet any of the following criteria:
• Has a documented diagnosis of MPS II and a has a neurocognitive testing score ≤ 77 (Bayley or Kaufman), 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 (Bayley or Kaufman) OR
• Has a relative clinically diagnosed with severe MPS II who has the same IDS mutation as the subject AND in the opinion of a geneticist has inherited a severe form of MPS II OR
• Has documented mutation (s) in IDS that in the opinion of a geneticist is always known to result in a neuronopathic phenotype AND in the opinion of a clinician has a severe form of MPS II
• 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
• Is a male ≥4 months to \< 5 years of age on Day 1
• Has a documented diagnosis of neuronopathic MPS II. Neuronopathic MPS II can be documented with any of the following methods:
• Has a BSID-III Cognitive Composite score at or below -1 SD (85) from normative mean
• Has two consecutive neurodevelopmental assessments that support a decline on MSEL visual receptive, expressive language, or fine motor, or BSID-III cognition, expressive language, or fine motor ≥ 1 SD on serial neurocognitive testing administered between 3 to 36 months apart
• Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the subject AND the subject, in the opinion of a geneticist, has inherited a neuronopathic form of MPS II
• Has documented mutation(s) in IDS known to result in a neuronopathic phenotype

You may not qualify if:

• Has contraindications for intracisternal (IC) injection, intracerebroventricular (ICV) injection or lumbar puncture
• Has contraindications for immunosuppressive therapy
• Has neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
• Has a (cerebral) ventricular shunt that may impact the proper dosing of the subject
• Received hematopoietic stem cell transplantation
• Has had prior treatment with an AAV-based gene therapy product
• Received ELAPRASE® via intrathecal (IT) administration within 4 months of signing the ICF or experienced a serious hypersensitivity reaction to ELAPRASE®
• Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer
• Has a contraindication for an IC injection, ICV injection or lumbar puncture
• Has contraindications for immunosuppressive therapy
• Has neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
• Has a (cerebral) ventricular shunt that may impact the proper dosing of the subject
• Received hematopoietic stem cell transplantation
• Has had prior treatment with an AAV-based gene therapy product
• Is receiving idursulfase (ELAPRASE®) via intrathecal (IT) administration, or a blood brain barrier-crossing enzyme replacement therapy. Subjects 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 24 months of follow-up

Sponsors & Collaborators

• REGENXBIO Inc.: lead

Study Sites (5)

University of California San Francisco, Benioff Children's Hospital

Oakland, California, 94609, United States

Location

St. Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh - UPMC: Program for Neurodevelopment in Rare Disorders

Pittsburgh, Pennsylvania, 15224, United States

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

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; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: June 21, 2018
• Study Start: September 27, 2018
• Primary Completion: November 27, 2023
• Study Completion: August 1, 2025
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); BR (1)