Phase I/II study of weekly infusions of JR-441 in patients with mucopolysaccharidosis type IIIA

Phase 1

• Conditions: Mucopolysaccharidosis type IIIA (MPS IIIA)MPS III is an autosomal recessive disease characterized by the accumulation of HS in the tissues throughout the body due to a deficiency in enzymes involved in glycosaminoglycan (GAG) degradation in lysosomes. In MPSIII type A the deficient enzyme is SGSH. MPS IIIA has an estimated birth prevalence of between 0.26 and 1.89 per 100,000 live births and manifests as a severe neurodegenerative disease with progressive developmental regression.; MedDRA version: 20.1Level: PTClassification code 10056890Term: Mucopolysaccharidosis IIISystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2022-002314-17-DE
• Lead Sponsor: JCR Pharmaceuticals Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-19
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

(1) Chronological age of =1 year and =18 years at time of signing ICF.
(2) A subject who voluntarily signs an IRB or IEC-approved written ICF. If the subject is aged =1 year to =18 years at the time of informed consent, or willingness to participate in the study cannot be confirmed due to MPS IIIA-related intellectual disability, the subject’s legally acceptable representative (e.g., his/her parents or guardians) may sign the ICF on behalf of the subject. Written informed assent must be obtained from the subject, wherever possible.
(3) A subject with a confirmed diagnosis of MPS IIIA, based on all the following criteria:
- Activity of the N-sulphoglucosamine sulphohydrolase (SGSH) enzyme below 10% of the lower reference level in white blood cells or cultured skin fibroblasts.
- A normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leukocytes.
- Presence of a pathological mutation in each of the individual alleles of the SGSH gene.
Note: if SGSH enzyme activity results are abnormal (i.e., below the normal range of the assay) but still above the threshold of 10% of the lower reference level, MPS IIIA diagnosis may be confirmed based on family history and genotype following discussion and approval from the sponsor’s Medical Monitor.
(4) Study subjects should have a minimal body weight of 10 kg.
(5) Female subjects of childbearing potential or subjects whose female partner is of child-bearing potential agree to use a medically accepted, highly effective method of contraception as described in Section 10.5, 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 or vasectomy at least 13 weeks prior to signing ICF.
(6) For subjects with hearing impairment requiring hearing aid(s), every effort has been made to encourage compliance with the use of functioning hearing aid(s) before baseline neurodevelopmental assessments, and parent/legally acceptable representative or subject agrees to encourage wearing them during the study and on neurodevelopmental function test days.
(7) Medically stable and able to accommodate the protocol requirements, including travel without placing an undue burden on the patient/patient’s family, as determined by the principal investigator.

Are the trial subjects under 18? yes
Number of subjects for this age range: 22
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

(1) A subject who has received gene therapy treatment or hematopoietic stem cell transplantation (HSCT) with successful engraftment.
(2) A subject who is pregnant or breast feeding.
(3) A subject who has received another investigational drug or product within 4 months or 5 half-lives (whichever is longer) before the time of providing informed consent.
(4) A subject who is participating concurrently or who has participated prior (within 30 days of enrolment into this study) in a study involving invasive procedures.
(5) A subject who has received Genistein within 4 months before the time of providing informed consent.
(6) A subject who has received KINERET® (anakinra) within 4 months before the time of providing informed consent.
(7) A subject who has developed serious drug allergy or hypersensitivity to any components of JR-441 or medications likely prescribed during the study, which, in the opinion of the principal investigator or sub-investigator, would be an impediment towards completion of the study.
(8) A subject unable to undergo lumbar puncture.
(9) A subject unable to undergo MRI.
(10) A subject who has had a ventriculoperitoneal (VP) shunt placed or any other brain surgery or has a clinically significant VP shunt malfunction within 30 days of screening (Subjects may be rescreened after the 30-day waiting period has elapsed).
(11) A subject has a history of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following lumbar puncture.
(12) A subject who has a history of poorly controlled seizures.
(13) Serology consistent with human immunodeficiency virus (HIV) exposure or consistent with active hepatitis B (HepB) or C (HepC) infection.
(14) A subject who has lab abnormalities with CTCAE grade = II for liver function test, bilirubin, creatinine, hemoglobin, white blood cell count, platelet count, prothrombin time, and activated partial thromboplastin time (aPTT), except subject whose bilirubin elevated due to Gilbert’s Syndrome.
(15) A subject with known iron-metabolism disorder.
(16) A subject with visual or hearing impairment sufficient, in the clinical judgment of the principal investigator or sub-investigator, to preclude cooperation with neurodevelopmental testing.
(17) A subject currently receiving psychotropic or other medications which in the principal investigator’s or sub-investigator’s opinion, would be likely to substantially confound test results.
(18) A subject who has a medical condition or extenuating circumstance that, in the opinion of the principal investigator or sub-investigator, might compromise the subject's ability to comply with protocol requirements, the subject's well-being or safety, or the interpretability of the subject's clinical data.
(19) A subject who is ineligible to participate in the study in the opinion of the principal investigator or sub-investigator.

Study & Design

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