A Study of JR-171 in Patients With Mucopolysaccharidosis I

Phase I/II Study of JR-171 ㏌ Patients With Mucopolysaccharidosis Type I

Phase I/II, open-label, multicenter, multinational (Japan, Brazil and US),designed to evaluate the safety, pharmacokinetics and explore the efficacy for the treatment of mucopolysaccharidosis type I (MPS I).

In the JR-171-102 study, subjects will receive either 2.0 or 4.0 mg/kg/week of JR-171 intravenously at the same dosages received at Week 12 of the JR-171-101 study.

Inclusion Criteria:

• A patient aged 18 years or older in Part 1 or any age in Part 2, at the time of informed consent
• A patient from whom written informed consent can be obtained. If the patient is aged under 18 years (20 years in case of Japan) at the time of assent or willingness to participate in the study cannot be confirmed due to MPS I-related intellectual disability, informed permission from the patient's legally acceptable representative (e.g. his/her parents or guardians) need to be obtained instead of his/her consent. Even in this case, written informed consent or assent should be obtained from the patient, wherever possible
• A patient diagnosed with MPS I based on any one of the following criteria:
• Activity of IDUA enzyme below 10% of lower reference level in leucocytes or cultured skin fibroblasts, AND increased age-related urinary levels of GAGs (before enzyme replacement therapy)
• Activity of IDUA enzyme below 10% of lower reference level in leucocytes or cultured skin fibroblasts, AND presence of one pathogenic mutation in each of the alleles of the IDUA gene
• Increased age-related urinary levels of GAGs (before enzyme replacement therapy), AND presence of one pathogenic mutation in each of the alleles of the IDUA gene
• A patient diagnosed as having no or mild MPS I-related intellectual disability (able to report their own subjective symptoms) by the principal investigator or subinvestigator (Part 1 only)
• A patient who has received laronidase continuously for at least 12 weeks and has received laronidase on a stable dosage for 2 weeks immediately before the initial administration of JR-171, except for a laronidase naïve patient or a patient who has previously been treated by HSCT)
• Female patient or male patient whose co-partner is of child-bearing potential agrees to use a medically accepted, highly effective method of contraception, such as spermatocidal gel plus condom, an intrauterine device or oral contraceptives until one month after the final administration

Exclusion Criteria:

• A patient who received gene therapy treatment
• A patient who, in the opinion of the principal investigator or subinvestigator, cannot undergo lumbar puncture, including those who have a difficulty in taking a position for lumbar puncture due to joint contracture and those who are likely to develop dyspnea during lumbar puncture
• A patient who is pregnant or lactating
• A patient who has developed serious drug allergy or hypersensitivity to any drugs, in the opinion of the principal investigator or subinvestigator, is inappropriate for participation in the study
• A patient who has received another investigational product within 12 months before enrollment in the study
• A patient who, in the opinion of the principal investigator or subinvestigator, is ineligible to participate in the study out of consideration for the participant safety.