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).

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis I
• Intervention / Treatment: Drug: JR-171 (lepunafusp alfa)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil
    • Hospital de Clinicas de Porto Alegre
  • São Paulo, Brazil
    • Instituto de Genética e Erros Inatos do Metabolismo - IGEIM
• Japan
  • Fukuoka, Japan
    • Fukuoka Children's Hospital
  • Nankoku, Japan
    • Kochi Medical School Hospital
  • Osaka, Japan
    • Osaka Metropolitan University Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part1 JR-171; Drug: JR-171 IV infusion, dose escalation	Drug: JR-171 (lepunafusp alfa); IV infusion
Experimental: Part2 JR-171; Drug: JR-171 IV infusion, dose escalation, low dose, high dose	Drug: JR-171 (lepunafusp alfa); IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	Time of the first dose of JR-171 until the last visit (Week 5 for Part 1/ Week 13 for Part 2).

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of Each Dose in Part 1 (AUC0-t)	Week 1 to Week 4
Pharmacokinetics of Each Dose in Part 1 (Cmax)	Week 1 to Week 4
Pharmacokinetics of Each Dose in Part 2 (AUC0-t)	Week 1 to Week 12
Pharmacokinetics of Each Dose in Part 2 (Cmax)	Week 1 to Week 12
Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 1	Baseline to Week 4
Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 1	Baseline to Week 4
Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 2	Baseline to Week 12
Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 2	Baseline to Week 12
Heparan Sulfate Concentrations in Serum in Part 1	Baseline to Week 5
Dermatan Sulfate Concentrations in Serum in Part 1	Baseline to Week 5
Heparan Sulfate Concentrations in Serum in Part 2	Baseline to Week 13
Dermatan Sulfate Concentrations in Serum in Part 2	Baseline to Week 13
Heparan Sulfate Concentrations in Urine in Part 1	Baseline to Week 5
Dermatan Sulfate Concentrations in Urine in Part 1	Baseline to Week 5
Heparan Sulfate Concentrations in Urine in Part 2	Baseline to Week 13
Dermatan Sulfate Concentrations in Urine in Part 2	Baseline to Week 13
Liver Volumes (Body Weight Adjusted) in Part 1	Baseline to Week 5
Spleen Volumes (Body Weight Adjusted) in Part 1	Baseline to Week 5
Liver Volumes (Body Weight Adjusted) in Part 2	Baseline to Week 13
Spleen Volumes (Body Weight Adjusted) in Part 2	Baseline to Week 13

Collaborators and Investigators

• Sponsor: JCR Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): August 2, 2022
• Study Completion (Actual): August 2, 2022

Study Registration Dates

• First Submitted: December 27, 2019
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: JR-171-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No