An Extension Study of JR-171-101 Study in Patients With MPS I

An Extension Study of JR-171-101 Study in Patients With Mucopolysaccharidosis Type I

Phase I/II, open label, multicenter, multinational (Japan, Brazil and the US) extension study of JR-171-101 for the treatment of MPS I

Study Overview

• Status: Active, not recruiting
• Conditions: Mucopolysaccharidosis I
• Intervention / Treatment: Drug: JR-171 (lepunafusp alfa)

Detailed Description

Patients who have completed the Part2 of JR-171-101 study and fulfill all eligibility criteria can be enrolled in this JR-171-102 study. Until the dose determination in the JR-171-102 study, subjects will intravenously receive either low dose or high dose of JR-171 at the same doses received at Week 12 of the JR-171-101 study. Thereafter, all subjects will be transitioned to the optimal dose determined based on the results of JR-171-101 study.

• Study Type: Interventional
• Enrollment (Actual): 14
• 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
  • Kitakyushu, Japan
    • National Hospital Organization Kokura Medical Center
  • 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: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have completed the Part 2 of JR-171-101 study
• 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 should be obtained from the patient, wherever possible
• Female patient or male patient whose co-partners is of child-bearing potential agree 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 is unable to perform the study procedures, except for 6-minute walk test, neurocognitive testing, BVMT-R, HVLT-R, and T.O.V.A.
• Judged by the principal investigator or subinvestigator as being unable to undergo lumbar puncture, including those who have difficulties in taking a position for lumbar puncture due to joint contracture or those who are likely to experience difficulty breathing during the lumbar puncture process
• Judged by the principal investigator or subinvestigator to be ineligible to participate in the study due to a history of a serious drug allergy or hypersensitivity to any drugs
• Otherwise judged by the principal investigator or subinvestigator to be ineligible to participate in the study in consideration of patient's safety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JR-171; Until the dose determination, subjects will intravenously receive either the low dose or high dose of JR-171 (the same dose as at Week 12 of the JR-171-101 study). Thereafter, all subjects will receive the optimal dose of JR-171 determined based on the results of JR-171-101 study.	Drug: JR-171 (lepunafusp alfa); JR-171 IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events	Adverse events	156 weeks
Incidence of abnormal laboratory test results	Hematology	156 weeks
Incidence of abnormal laboratory test results	Biochemistry	156 weeks
Incidence of abnormal laboratory test results	Serum iron tests	156 weeks
Incidence of abnormal laboratory test results	Urinalysis	156 weeks
Incidence of abnormal vital signs	Pulse rate	156 weeks
Incidence of abnormal vital signs	Body temperature	156 weeks
Incidence of abnormal vital signs	Blood pressure	156 weeks
Incidence of abnormal vital signs	Body weight	156 weeks
Incidence of abnormal EKG readings		156 weeks
Number of participants with Adverse Events	Anti-human-α-L-iduronidase antibodies	156 weeks
Number of participants with Adverse Events	Anti-JR-171 antibodies	156 weeks
Number of participants with Adverse Events	Infusion associated reaction (IAR)	156 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid		Weeks 26, 52, 104, 156
Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid		Weeks 26, 52, 104, 156
CSF opening pressure		Weeks 26, 52, 104, 156
Change From Baseline in Heparan Sulfate Levels in Urinary		Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
Change From Baseline in Dermatan Sulfate Levels in Urinary		Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
Change From Baseline in Heparan Sulfate Levels in Serum		Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
Change From Baseline in Dermatan Sulfate Levels in Serum		Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
Change From Baseline in Liver Volume		Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Spleen Volume.		Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	Left ventricular posterior wall thickness	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	interventricular septal thickness	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	left ventricular mass index	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	left ventricular ejection fraction	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	left ventricular ejection fraction,	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in Echocardiography.	E/A ratio	Weeks 13, 26, 52, 78, 104, 156
Change From Baseline in 6-minute Walk Test Distance.		Weeks 13, 26, 52, 78, 104, 156
Changes from baseline in cognitive age equivalent score of neurocognitive testing	Wechsler IQ test or the Bayley scales of infant and toddler development	Weeks 52, 104, 156
Changes from baseline in outcome of adaptive behavioral function	Vineland adaptive behavior scales	Weeks 52, 104, 156
Changes from baseline in outcome of the Brief Visuospatial Memory Test-Revised		Weeks 13, 26, 52, 78, 104, 130, 156
Changes from baseline in outcome of the Hopkins Verbal Learning Test-Revised		Weeks 13, 26, 52, 78, 104, 130, 156
Changes from baseline in outcome of the Test of Variables of Attention		Weeks 13, 26, 52, 78, 104, 130, 156
Changes from baseline in outcome of the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)		Weeks 13, 26, 52, 104 156

Collaborators and Investigators

• Sponsor: JCR Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Mucopolysaccharidosis I
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: JR-171-102

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