A Phase III study of JR-141 in Hunter Syndrome patients

Phase 1

• Conditions: Mucopolysaccharidosis type II; MedDRA version: 20.1Level: PTClassification code 10056889Term: Mucopolysaccharidosis IISystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2020-003200-14-IT
• Lead Sponsor: JCR Pharmaceutical Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-08-21
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 80

Inclusion Criteria

1. A patient who voluntarily signs an IRB or Independent Ethics Committee (IEC)-approved written ICF. If the patient is aged under 18 years (aged under 16 years in the UK) at the time of enrollment or willingness to participate in the study cannot be confirmed due to MPS II-related intellectual disability, the patient's legally acceptable representative (e.g., his parents or guardians) may sign the informed
consent on behalf of the patient. Written informed assent should be obtained from the patient, wherever possible.
2. Males with confirmed diagnosis of MPS II, based on all of the following criteria:
1) Deficient activity of IDS in leucocytes, plasma or fibroblasts defined by 10% or less of the lower limit of the measuring laboratory normal range unless the hospital or laboratory has established different criteria
2) Documented mutation identified in the IDS gene
3) Increased levels of urinary glycosaminoglycans (GAGs) (or uronic acid) or clinical symptoms and signs consistent with MPS II (such as dysostosis multiplex, coarse facies, cardiac valve disease, neuronopathic, chronic pulmonary disease, hernias, kyphosis, joint contractures, carpal tunnel syndrome, etc)
3. Naïve subjects or patients who are receiving stable enzyme replacement therapy (ERT) with idursulfase for more than 12 weeks before starting administration of JR-141 or idursulfase for this study.
4. Cohort A
- Males aged 36-42 months old: patients must have a standard score on the cognitive domain measured by the BSID-III of 85 or less at screening
- Males aged 43-71 months old: patients must EITHER have
1. A development quotient (DQ) on the cognitive domain measured by the BSID-III between 20 and 85 at screening
2. A composite standard score on Nonverbal Index (NVI) measured by the KABC-II of 85 or less at screening for only who are able to perform the KABC-II
- Males aged 30-35 months old at the time of randomization and who are judged as having the severe phenotype by the Expert Board based on presence of one of the following mutations in the IDS gene and other information such as high CSF HS concentrations:
1) Large deletion or rearrangement
2) Small insertions or deletions that are out of frame
3) Missense mutations, nonsense mutations, in frame inserts or deletions that involve neuronopathic disease in either another family or the patient's family members.
5. Cohort B
- Males aged 6 years or older at the time of ICF signing and whose intelligence quotient (IQ) on the Wechsler test (either WISC-V, or WAIS-IV) is 70 and higher at screening
- Patients with 1SD deficiency in the omission errors or variability domains of the T.O.V.A. test or Processing Speed or Working memory on the Wechsler tests at screening
PLEASE REFER TO THE PROTOCOL FOR FURTHER DETAILS
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. A patient with a history of engrafted hematopoietic stem cell transplantation (HSCT), with successful engraftment.
2. A patient who has received gene therapy treatment at any point.
3. A patient who is judged by the principal investigator or sub- investigator as being unable to undergo lumbar puncture, including those who has difficulties in taking position for lumbar puncture due to joint contracture or those who is likely to experience breathing
difficulties during the lumbar puncture process.
4. A patient who is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 4 months before obtaining informed consent.
5. A patient who is unable to comply with the protocol (e.g., is unable to return for safety evaluations or is otherwise unlikely to complete the study) as determined by the principal investigator or sub-investigator.
6. A patient who is judged by the principal investigator or sub- investigator to be ineligible to participate in the study due to a history of serious drug allergy or sensitivity including anesthesia or hypersensitivity to any component of JR-141 or idursulfase.
7. A patient who has a known or suspected local or general infection or is at risk of abnormal bleeding due to medical conditions* or therapies.
8. A patient who has documented mutation of other genes, including loci adjacent to the IDS gene (e.g., fragile X mental retardation [FMR1] or AF4/FMR2 family member 2[i.e., AFF2 or FMR2]), that are known to be associated with developmental delay, seizures, or other significant CNS disorders.
PLEASE REFER TO THE PROTOCOL FOR FURTHER DETAILS

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified