A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)

Official title

A Global, Open-Label, Phase I/II Trial, to Evaluate Safety, Tolerability, Pharmacodynamic and Preliminary Efficacy of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)

Overview

This is a global, open-label, Phase I/II, interventional trial in participants younger than 6 years of age with Mucopolysaccharidosis Type IIIB (MPS IIIB), designed to assess the safety and tolerability of JR-446, determine its pharmacodynamic effects, and explore its potential to demonstrate early clinical effects on disease-relevant outcomes.

Interventions

• Drug JR-446
  IV infusion

Primary outcome measures

• To establish the safety and tolerability of JR-446 in MPS IIIB patients following repeated dose administration [Time frame: Up to 1 year (multiple visits)]

Secondary outcome measures (12)

• Change From Baseline in Cerebrospinal Fluid Heparan Sulfate Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Absolute Change From Baseline in Serum Heparan Sulfate Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Percent Change From Baseline in Serum Heparan Sulfate Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Absolute Change From Baseline in Urine Heparan Sulfate Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Percent Change From Baseline in Urine Heparan Sulfate Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Absolute Change From Baseline in Serum Neurofilament Light Chain Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Percent Change From Baseline in Serum Neurofilament Light Chain Concentration [Time frame: Through Week 53 (up to 1 year; multiple visits)]
• Change in Cognitive Function Assessments From Baseline [Time frame: Through Week 53 (up to 1 year)]
• Change in Brain MRIs From Baseline [Time frame: Through Week 53 (up to 1 year)]
• Change in Height Standard Deviation Score (SDS) From Baseline (using WHO child growth standards) [Time frame: Through Week 53 (up to 1 year)]
• Change in Weight SDS From Baseline (using WHO child growth standards) [Time frame: Through Week 53 (up to 1 year)]
• Change in Body Mass Index (BMI) SDS From Baseline (using WHO child growth standards) [Time frame: Through Week 53 (up to 1 year)]

Eligibility criteria

Inclusion criteria

• Patients with confirmed MPS IIIB with a phenotype of MPS IIIB that is not classified as slowly progressive (i.e., not attenuated).
• A chronological age <6 years.
• Ability to complete and achieve a Standard score ≥55, using either Bailey Scale of Infant Development-4 (BSID-4) Cognitive domain or Kaufman Assessment Battery for Children-II (KABC-II) Non-Verbal Index, whichever tool is most appropriate for the participant's chronological age.

Exclusion criteria

• Contraindication for lumbar puncture or MRI.
• A 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.
• A participant who has received any other investigational drug product (including but not limited to, tralesinidase alfa enzyme replacement therapy \[TA-ERT\], Genistein, KINERET \[anakinra\], ambroxol, miglustat) within 4 months (or 5 half-lives, whichever is longer) before the time of providing informed consent.
• A participant who has received gene therapy treatment or hematopoietic stem cell transplantation (HSCT) with successful engraftment.
• Serious drug allergy or hypersensitivity to any components of JR-446 or medications likely prescribed during the trial.
• A 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.
• A patient with recurrent epileptic seizures not adequately controlled with anti-seizure medication, and which, in the clinical judgment of the principal investigator, would preclude safe participation in the trial.
• Serology consistent with human immunodeficiency virus (HIV) exposure or consistent with active hepatitis B (HepB) or hepatitis C (HepC) infection.
• A participant/family, who, in the opinion of the investigator, may not be able to comply with protocol requirements and cooperate fully with the trial assessments, procedures, and scheduling for JR-446 IMP dose administrations.
• Study participants for whom informed consent is unable to be provided by a parent or legal guardian; or when applicable for a study participant who is unable to provide assent with respect to study participation in conjunction with parental or legal guardian consent for participation on study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Children's Hospital Oakland Research Institution, Attn: 2900 Wing — Oakland
• UPMC Children's Hospital of Pittsburgh — Pittsburgh
• Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) — Fairfax

Germany · 1 center

• University Medical Center Hamburg-Eppendorf — Hamburg

United Kingdom · 1 center

• Great Ormond Street Hospital for Children — London

Identifiers

NCT: NCT07640984 · JR-446-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗