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

• ClinicalTrials.gov Identifier: NCT04453085
• Recruitment Status: Active, not recruiting
• First Posted: July 1, 2020
• Last Update Posted: March 15, 2024
• Sponsor: JCR Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): JCR Pharmaceuticals Co., Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis I	Drug: JR-171 (lepunafusp alfa)	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Extension Study of JR-171-101 Study in Patients With Mucopolysaccharidosis Type I
• Actual Study Start Date: October 28, 2021
• Estimated Primary Completion Date: April 30, 2025
• Estimated Study Completion Date: April 30, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with Adverse Events [ Time Frame: 156 weeks ]
   Adverse events
2. Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
   Hematology
3. Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
   Biochemistry
4. Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
   Serum iron tests
5. Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
   Urinalysis
6. Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
   Pulse rate
7. Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
   Body temperature
8. Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
   Blood pressure
9. Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
   Body weight
10. Incidence of abnormal EKG readings [ Time Frame: 156 weeks ]
11. Number of participants with Adverse Events [ Time Frame: 156 weeks ]
    Anti-human-α-L-iduronidase antibodies
12. Number of participants with Adverse Events [ Time Frame: 156 weeks ]
    Anti-JR-171 antibodies
13. Number of participants with Adverse Events [ Time Frame: 156 weeks ]
    Infusion associated reaction (IAR)

Secondary Outcome Measures :

1. Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Weeks 26, 52, 104, 156 ]
2. Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Weeks 26, 52, 104, 156 ]
3. CSF opening pressure [ Time Frame: Weeks 26, 52, 104, 156 ]
4. Change From Baseline in Heparan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
5. Change From Baseline in Dermatan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
6. Change From Baseline in Heparan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
7. Change From Baseline in Dermatan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
8. Change From Baseline in Liver Volume [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
9. Change From Baseline in Spleen Volume. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
10. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    Left ventricular posterior wall thickness
11. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    interventricular septal thickness
12. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    left ventricular mass index
13. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    left ventricular ejection fraction
14. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    left ventricular ejection fraction,
15. Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
    E/A ratio
16. Change From Baseline in 6-minute Walk Test Distance. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
17. Changes from baseline in cognitive age equivalent score of neurocognitive testing [ Time Frame: Weeks 52, 104, 156 ]
    Wechsler IQ test or the Bayley scales of infant and toddler development
18. Changes from baseline in outcome of adaptive behavioral function [ Time Frame: Weeks 52, 104, 156 ]
    Vineland adaptive behavior scales
19. Changes from baseline in outcome of the Brief Visuospatial Memory Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
20. Changes from baseline in outcome of the Hopkins Verbal Learning Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
21. Changes from baseline in outcome of the Test of Variables of Attention [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
22. Changes from baseline in outcome of the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM) [ Time Frame: Weeks 13, 26, 52, 104 156 ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States, 94609

Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Instituto de Genética e Erros Inatos do Metabolismo - IGEIM

São Paulo, Brazil

Japan

Fukuoka Children's Hospital

Fukuoka, Japan

National Hospital Organization Kokura Medical Center

Kitakyushu, Japan

Osaka Metropolitan University Hospital

Osaka, Japan

Sponsors and Collaborators

JCR Pharmaceuticals Co., Ltd.

More Information

• Responsible Party: JCR Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04453085
• Other Study ID Numbers: JR-171-102
• First Posted: July 1, 2020
• Last Update Posted: March 15, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by JCR Pharmaceuticals Co., Ltd.:

Mucopolysaccharidosis I

Additional relevant MeSH terms:

Mucopolysaccharidoses; Mucopolysaccharidosis I; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases