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Trial record 1 of 1 for:    NCT03566043
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CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03566043
Recruitment Status : Active, not recruiting
First Posted : June 21, 2018
Last Update Posted : November 18, 2023
Sponsor:
Information provided by (Responsible Party):
REGENXBIO Inc.

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type II (MPS II) Genetic: RGX-121 Phase 2 Phase 3

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) (neurocognition 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 I/II/III study enrolling in two sequential parts. Part 1 is a Phase I/II, first-in-human, multicenter, open-label, single arm dose escalation study of RGX-121. Three one-time doses of RGX-121 will be studied in up to 16 pediatric subjects who have neuronopathic MPS II. Safety will be the primary focus for the initial 24 weeks after treatment (primary study period) whereupon, subjects will continue to be assessed (safety and efficacy) for up to a total of 104 weeks following treatment with RGX-121. Part 2 is a pivotal expansion, multicenter, open-label, single arm study of RGX-121. A single dose of RGX-121 will be studied in up to 30 pediatric patients who have been diagnosed with neuronopathic MPS II. Subjects will be assessed at various timepoints for 24 months after receiving RGX-121. Subjects will be given the opportunity to enroll in a separate 3-year long-term follow-up study in accordance with the US federal government guidelines for the safety follow-up of patients receiving gene therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Dose escalation
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2/3 Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of RGX-121 in Pediatric Subjects With MPS II (Hunter Syndrome)
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2025


Arm Intervention/treatment
Experimental: Part 1: RGX-121 Dose 1
1.3x10^10 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Part 1: RGX-121 Dose 2
6.5x10^10 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Part 1: RGX-121 Dose 2 Expanded Cohort
6.5x10^10 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Part 1: RGX-121 Dose 3
2.0x10^11 GC/g brain mass of RGX-121
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Part 1: RGX-121 Dose 3 Expanded Cohort
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
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette

Experimental: Part 2: RGX-121 Pivotal Expansion
2.9x10^11 GC/g brain mass of RGX-121 (transgene-specific PCR assay)
Genetic: RGX-121
Recombinant adeno-associated virus serotype 9 capsid containing human iduronate-2-sulfatase expression cassette




Primary Outcome Measures :
  1. Part 1 Safety [ Time Frame: 24 Weeks ]
    Number of participants with treatment-related adverse events and serious adverse events as assessed by CTCAE (Version 4.03).

  2. Part 2 Biomarkers [ Time Frame: 52 Weeks ]
    CSF GAG levels (as measured by D2S6)

  3. Part 2 Biomarkers [ Time Frame: 104 weeks ]
    CSF GAG levels (as measured by D2S6)

  4. Part 2 Neurodevelopmental parameters [ Time Frame: 52 Weeks ]
    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.

  5. Part 2 Neurodevelopmental parameters [ Time Frame: 104 weeks ]
    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.


Secondary Outcome Measures :
  1. Part 1 Safety [ Time Frame: 104 Weeks ]
    Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)

  2. Part 1 Biomarkers [ Time Frame: 104 Weeks ]
    Glycosaminoglycan levels and iduronate-2-sulfatase activity

  3. Part 1 Neurodevelopmental parameters [ Time Frame: 104 Weeks ]
    Neurodevelopment parameters of cognitive, behavioral & 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) and Mullen Scales of Early Learning (MSEL). The BSID-III evaluates the developmental functioning of infants & small children 1 to 42 months old to identify developmental delays. The KABC-II measures cognitive skill & academic knowledge to evaluate knowledge acquired & level of school learning attained. This test evaluates children 2.5 to 12.5 years old in 4 dimensions: mental, sequential and simultaneous processing, & knowledge. The MSEL measures cognitive ability language & motor development & has 5 scales: gross & fine motor, visual reception, & receptive and expressive language. An increase in raw & age equivalent scores indicates neurodevelopmental skill acquisition. Standard scores compare function to age matched normative data.

  4. Part 1 Change in neurodevelopmental parameters [ Time Frame: 104 Weeks ]
    Neurodevelopment parameters of cognitive, behavioral and adaptive function 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.

  5. Part 2 Change in neurodevelopmental parameters [ Time Frame: 52 Weeks ]
    Change from baseline in neurodevelopment effect 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.

  6. Part 2 Change in brain magnetic resonance imaging (MRI) parameters [ Time Frame: 52 Weeks ]
    Change from baseline in brain size as measured on MRI

  7. Part 2 Safety [ Time Frame: 24 Months ]
    Number of participants with treatment-related adverse events as assessed by CTCAE (Version 4.03)

  8. Part 2 Biomarkers [ Time Frame: 24 Months ]
    Change in Glycosaminoglycan levels and iduronate-2-sulfatase activity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Months to 5 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Genetic-based gender identity
Accepts Healthy Volunteers:   No
Criteria

Part 1 Inclusion Criteria:

  • 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

Part 2 Inclusion Criteria:

  • 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

Part 1 Exclusion Criteria:

  • 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

Part 2 Exclusion Criteria:

  • 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
  • Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03566043


Locations
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United States, California
University of California San Francisco, Benioff Children's Hospital
Oakland, California, United States, 94609
United States, New Jersey
St. Peter's University Hospital
New Brunswick, New Jersey, United States, 08901
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh - UPMC: Program for Neurodevelopment in Rare Disorders
Pittsburgh, Pennsylvania, United States, 15224
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, RS, Brazil, 90035-903
Sponsors and Collaborators
REGENXBIO Inc.
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Responsible Party: REGENXBIO Inc.
ClinicalTrials.gov Identifier: NCT03566043    
Other Study ID Numbers: RGX-121-101
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: November 18, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by REGENXBIO Inc.:
MPS II
gene therapy
Hunter Syndrome
Lysosomal Storage Disorder
Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System