A Study of JR-171 in Patients With Mucopolysaccharidosis I

Phase 1

Completed

• Conditions: Mucopolysaccharidosis I
• Interventions: Drug: JR-171 (lepunafusp alfa)

• Registration Number: NCT04227600
• Lead Sponsor: JCR Pharmaceuticals Co., Ltd.

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-27
• Study First Submitted QC: 2020-01-10
• Study First Posted: 2020-01-13
• Study Start: 2020-09-01
• Primary Completion: 2022-08-02
• Study Completion: 2022-08-02
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-12
• Last Update Posted: 2022-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part1 JR-171	JR-171 (lepunafusp alfa)	Drug: JR-171 IV infusion, dose escalation
Part2 JR-171	JR-171 (lepunafusp alfa)	Drug: JR-171 IV infusion, dose escalation, low dose, high dose

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse Events	13 Week	Infusion associated reaction (IAR)

Secondary Outcome Measures

Name	Time	Method
Assessment of plasma drug concentration	Part1: 1,2,3,4 week, Part2: 1,4,12 week
Change From Baseline in Liver Volume.	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Change From Baseline in 6-minute Walk Test Distance.	Part 2: Baseline, 13 week
Change From Baseline in T.O.V.A.	Part 2: Baseline, 13 week
Change From Baseline Drug concentration in Cerebrospinal Fluid.	Part1: Baseline, 4 week Part2: Baseline, 12 week
Change From Baseline in Heparan Sulfate Levels in Urinary	Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Change From Baseline Opening pressure in Cerebrospinal Fluid	Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Change From Baseline in Echocardiography.	Part 1: Baseline, 5 week Part 2: Baseline, 13 week	E/A ratio
Change From Baseline in BVMT-R	Part 2: Baseline, 13 week
Change From Baseline in PedsQL-FIM	Part 2: Baseline, 13 week
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid	Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid	Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Change From Baseline in Dermatan Sulfate Levels in Serum	Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Change From Baseline in Dermatan Sulfate Levels in Urinary	Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Assessment of pharmacokinetic parameter	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week	Mean residence time from time zero to the last blood sampling time point \[MRT0-t\]
Change From Baseline in Heparan Sulfate Levels in Serum	Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Change From Baseline in Spleen Volume.	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Change From Baseline in HVLT-R	Part 2: Baseline, 13 week

Trial Locations

Locations (6)

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

UCSF Benioff Children's Hospital Oakland; 🇺🇸 Oakland, California, United States

Fukuoka Children's Hospital; 🇯🇵 Fukuoka, Japan

Instituto de Genética e Erros Inatos do Metabolismo - IGEIM; 🇧🇷 São Paulo, Brazil

Kochi Medical School Hospital; 🇯🇵 Nankoku, Japan

Osaka Metropolitan University Hospital; 🇯🇵 Osaka, Japan