N-SULFOGLUCOSAMINE SULFOHYDROLASE FUSED TO A HUMANISED MONOCLONAL ANTIBODY TARGETING HUMAN TRANSFERRIN RECEPTOR for Mucopolysaccharidosis type IIIA (MPS IIIA)

Inclusion criteria

• {"criterion_text":"- (1) Chronological age of ≥1 year and ≤18 years at the time of signing ICF."}
• {"criterion_text":"- (2) A participant who voluntarily signs an IRB or IEC-approved written ICF. If the participant is aged 1year 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 participant’s legally acceptable representative (e.g., his/her parents or guardians) may sign the ICF on behalf of the participant. Written informed assent must be obtained from the participant, wherever possible.."}
• {"criterion_text":"- (3) A participant 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."}
• {"criterion_text":"- (4) Study participants should have a minimal body weight of 10 kg."}
• {"criterion_text":"- (5)\tFemale participants of childbearing potential or participants 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 participants, and 30 days for female participants after the final study drug administration or vasectomy at least 13 weeks prior to signing ICF.."}
• {"criterion_text":"- (6)\tFor participants 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 participant agrees to encourage wearing them during the study and on neurodevelopmental function test days."}
• {"criterion_text":"- (7)\tMedically stable and able to accommodate the protocol requirements, including travel without placing an undue burden on the participant/participant’s family, as determined by the principal investigator."}

Exclusion criteria

• {"criterion_text":"- (1) A participant who has received gene therapy treatment or hematopoietic stem cell transplantation (HSCT) with successful engraftment."}
• {"criterion_text":"- (10)\tA participant who has had a ventriculoperitoneal (VP) shunt placed or any other brain surgery"}
• {"criterion_text":"- (11)\tA participant 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."}
• {"criterion_text":"- (12)\tA participant who has a history of poorly controlled seizures."}
• {"criterion_text":"- (13)\tSerology consistent with human immunodeficiency virus (HIV) exposure or consistent with active hepatitis B (HepB) or C (HepC) infection."}
• {"criterion_text":"- (14)\tA participant 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."}
• {"criterion_text":"- (15) A participant with known iron-metabolism disorder."}
• {"criterion_text":"- (16)\tA participant with visual or hearing impairment sufficient, in the clinical judgment of the principal investigator or sub-investigator, to preclude cooperation with neurodevelopmental testing."}
• {"criterion_text":"- (17)\tA participant 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."}
• {"criterion_text":"- (18)\tA participant who has a medical condition or extenuating circumstance that, in the opinion of the principal investigator or sub-investigator, might compromise the participant’s ability to comply with protocol requirements, the participant’s well-being or safety, or the interpretability of the participant’s clinical data."}
• {"criterion_text":"- (19)\tA participant who is ineligible to participate in the study in the opinion of the principal investigator or sub-investigator."}
• {"criterion_text":"- (2) A participant who is pregnant or breast feeding."}
• {"criterion_text":"- (3)\tA participant 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."}
• {"criterion_text":"- (4)\tA participant who is participating concurrently or who has participated prior (within 30 days of enrolment into this study) in a study involving invasive procedures."}
• {"criterion_text":"- (5)\tA participant who has received Genistein within 4 months before the time of providing informed consent."}
• {"criterion_text":"- (6)\tA participant who has received KINERET® (anakinra) within 4 months before the time of providing informed consent."}
• {"criterion_text":"- (7)\tA participant 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."}
• {"criterion_text":"- (8)\tA participant unable to undergo lumbar puncture."}
• {"criterion_text":"- (9)\tA participant unable to undergo MRI."}

Primary endpoints

• {"endpoint_text":"- 1. Occurrence of adverse events (AEs)","definition_or_measurement_approach":"Occurrence and reporting of adverse events (AEs) as recorded during the study."}
• {"endpoint_text":"- 2. Changes in safety laboratory tests (hematology, coagulation, blood biochemistry, iron-related tests, and urinalysis)","definition_or_measurement_approach":"Changes from baseline in specified laboratory parameters: hematology, coagulation, blood biochemistry, iron-related tests, and urinalysis."}
• {"endpoint_text":"- 3. Changes in vital signs (pulse rate, body temperature, blood pressure, respiratory rate, and percutaneous oxygen saturation)","definition_or_measurement_approach":"Changes from baseline in vital sign measurements: pulse rate, body temperature, blood pressure, respiratory rate, and percutaneous oxygen saturation."}
• {"endpoint_text":"- 4. Changes in 12-lead electrocardiogram (ECG)","definition_or_measurement_approach":"Changes from baseline in 12-lead ECG recordings."}
• {"endpoint_text":"- 5. Number and severity of infusion-associated reactions (IARs), occurrence of anaphylaxis","definition_or_measurement_approach":"Recording and grading of infusion-associated reactions (IARs) and any occurrences of anaphylaxis during or after infusions."}

Secondary endpoints

• {"endpoint_text":"- 1. Plasma drug concentration","definition_or_measurement_approach":"Measurement of JR-441 concentration in plasma samples."}
• {"endpoint_text":"- 2. Plasma PK parameters","definition_or_measurement_approach":"Determination of pharmacokinetic parameters derived from plasma concentration-time data."}
• {"endpoint_text":"- 3. Changes in the following parameters from baseline to each evaluation time point: (1) Heparan sulfate (HS concentration in CSF and serum, and HS concentration relative to creatinine concentration in urine. (2) Cognitive function assessed by Cognitive scales and/or Nonverbal Index (NVI); (3) Adaptive behavior assessment","definition_or_measurement_approach":"Changes from baseline in HS concentrations in CSF and serum and urinary HS/creatinine, cognitive function assessed via cognitive scales and/or Nonverbal Index (NVI), and adaptive behavior assessments."}

Germany

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

563

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Jcr Pharmaceuticals Co. Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Japan

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Project management and multiple study operational responsibilities (sponsorDuties include project management and multiple functional codes).

Name

Primevigilance Limited

Responsibilities

PV Vendor

Name

Frontage Laboratories Inc.

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"cognitive testing/ questionnaires","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"PV Vendor","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Marken","duties_or_roles":"Sample transportation","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Drug depot","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Provide lab kit","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Training and preparing manuals for 2-minute walk and 4-stair climb tests","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"travel/ reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Project management (multiple operational responsibilities; codes: 1,2,3,4,6,7,8,10,11,12,15 etc.)","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Shin Nippon Biomedical Laboratories Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}