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

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

Detailed Description
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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.

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

Conditions
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Mucopolysaccharidosis I

Intervention / Treatment
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* Drug: JR-171 (lepunafusp alfa)


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JR-171<br>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)<br>* JR-171 IV infusion<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mucopolysaccharidosis I