Clinical trial NCT05594992: An Extension Study of JR-141 to Evaluate the Long-term Safety and Efficacy in Mucopolysaccharidosis Type II (Hunter Syndrome) Subjects
Official title: An Extension Study of JR-141 to Evaluate the Long-term Safety and Efficacy in Mucopolysaccharidosis Type II (Hunter Syndrome) Subjects
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Mucopolysaccharidosis II
Lead sponsor: JCR Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-10-26
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An extension of Global Phase III open-label, multicenter designed to evaluate the Long-term safety and efficacy of study drug for the treatment of the MPS II.


Eligibility criteria: Inclusion Criteria:

1. A subject who participated in the Parent Study (JR-141-GS31) and completed the assessments at Week 105 in Cohort A or Week 53 in Cohort B, and in the opinion of the principal investigator has no safety concerns to enter this study.
2. A subject from whom an IRB or IEC-approved written informed consent can be obtained, which is voluntarily signed. If the subject 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 subject's legally acceptable representative (e.g., his parents or guardians) may sign the ICF on behalf of the subject. Written informed assent should be obtained from the subject, wherever possible.
3. Female subject of child bearing potential or male subject whose female partner is of child-bearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile, agrees to use a medically accepted, highly effective method of contraception from the time of signing the ICF. The method of contraception must be used during the study until 90 days for male subjects, and 30 days for female subjects after the final study drug administration.

Exclusion Criteria:

1. A subject who has received gene therapy treatment at any point.
2. Refusal to sign the ICF.
3. A subject who is judged by the principal investigator or sub-investigator as being unable to undergo lumbar puncture, including those who have difficulties in attaining the required position for lumbar puncture due to joint contracture or those who are likely to experience breathing difficulties during the lumbar puncture process.
4. A subject who changed treatment from JR-141 to idursulfase during the treatment period in the Parent Study (JR-141-GS31).
5. A subject 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 subject 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 to anesthesia or hypersensitivity to any component of JR-141.
7. A subject who has a known or suspected local or general chronic infection or is at risk of abnormal bleeding due to medical conditions\* or therapies the investigator classifies as causing the patient to be ineligible to participate in the study.
8. A subject who otherwise is judged by the principal investigator or sub-investigator to be ineligible to participate in the study .
9. \[Only in France\] Persons deprived of their liberty by a judicial or administrative decision, according to article L. 1121-6 of the Public Health Code (Code de la santé publique, CSP) adults who are the subject of a measure of legal protection or unable to express their consent according to article L. 1121-8 of the CSP.

Medical Conditions:

1. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA, toxic epidermal necrolysis, and exfoliative dermatitis)
2. Evidence or history of significant active bleeding or coagulation disorder or use of non steroidal anti-inflammatory drugs or other drugs that affect coagulation or platelet function within 14 days prior to lumbar catheter insertion
3. Allergy to lidocaine (Xylocaine®) or its derivatives

Primary outcomes:
measure: Change in heparan sulfate concentrations in cerebrospinal fluid from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study to each time point
timeFrame: [A-1, A-2, A-3: Week 157, 209, 261] [A-4: Week 131, 183, 235, 287]
measure: Change in neurocognitive testing, calculated by the BSID-III or KABC-II, from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study
timeFrame: [A-1: Week 157, 209, 261] [A-2: Week 131, 157, 183, 209, 261] [A-3: Week 131, 157, 209, 261 ] [A-4: Week 131, 157, 183, 235, 287]
measure: Change in neurocognitive testing, calculated by the VABS-II from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study
timeFrame: [A-1: Week 157, 209, 261] [A-2: Week 131, 157, 183, 209, 261] [A-3: Week 131, 157, 209, 261 ] [A-4: Week 131, 157, 183, 235, 287][B-1: Week 78, 105, 157, 209, 261] [B-2: Week 78, 105, 131, 157, 209, 261]
measure: Change in neurocognitive testing, calculated by the Wechsler, from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study
timeFrame: [B-1: Week 78, 105, 157, 209, 261] [B-2: Week 78, 105, 131, 157, 209, 261]
Secondary outcomes:
measure: Change in liver and spleen volume from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study
timeFrame: [A-1, A-3: Week 157, 209, 261] [A-2: Week 131, 157, 209, 261] [A-4: Week 131, 183, 235, 287] [B-1: Week 105, 157, 209, 261] [B-2: Week 78, 105, 157, 209, 261]
measure: Change in 6-minute walk distance from each subject's first administration of JR-141 throughout the Parent Study (JR-141-GS31) or this study
timeFrame: [B-1: Week 105, 157, 209, 261] [B-2: Week 78, 105, 157, 209, 261]
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Instituto de Genética e Erros Inatos do Metabolismo
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Rome
country: Italy
facility: Osp. Pediatrico Bambino Gesù, IRCCS
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
Study officials:
References: