- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04227600
A Study of JR-171 in Patients With Mucopolysaccharidosis I
December 12, 2022 updated by: JCR Pharmaceuticals Co., Ltd.
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
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Porto Alegre, Brazil
- Hospital de Clínicas de Porto Alegre
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São Paulo, Brazil
- Instituto de Genética e Erros Inatos do Metabolismo - IGEIM
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Fukuoka, Japan
- Fukuoka Children's Hospital
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Nankoku, Japan
- Kochi Medical School Hospital
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Osaka, Japan
- Osaka Metropolitan university Hospital
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California
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Oakland, California, United States, 94609
- UCSF Benioff Children's Hospital Oakland
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part1 JR-171
Drug: JR-171 IV infusion, dose escalation
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IV infusion
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Experimental: Part2 JR-171
Drug: JR-171 IV infusion, dose escalation, low dose, high dose
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IV infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with Adverse Events
Time Frame: 13 Week
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Adverse events
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13 Week
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Number of participants with Adverse Events
Time Frame: 13 Week
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Laboratory tests (hematology, biochemistry, serum iron tests, and urinalysis)
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13 Week
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Number of participants with Adverse Events
Time Frame: 13 Week
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Vital signs (pulse rate, body temperature, blood pressure, respiratory rate and percutaneous oxygen saturation)
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13 Week
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Number of participants with Adverse Events
Time Frame: 13 Week
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12-lead electrocardiogram
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13 Week
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Number of participants with Adverse Events
Time Frame: 13 Week
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Antibodies [anti-human-α-L-iduronidase (anti-IDUA) and anti-JR-171 antibodies]
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13 Week
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Number of participants with Adverse Events
Time Frame: 13 Week
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Infusion associated reaction (IAR)
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13 Week
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of plasma drug concentration
Time Frame: Part1: 1,2,3,4 week, Part2: 1,4,12 week
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Part1: 1,2,3,4 week, Part2: 1,4,12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Maximum Plasma Concentration[Cmax]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Area Under the Curve from time zero to the last blood sampling time point[AUC0-t]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Area Under the Curve from time zero to infinity [AUC0-∞]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
|
Time to reach maximum plasma concentration [tmax]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
|
Elimination half-life [t1/2]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
|
Elimination rate constant [kel]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Assessment of pharmacokinetic parameter
Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Mean residence time from time zero to the last blood sampling time point [MRT0-t]
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Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
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Change From Baseline Drug concentration in Cerebrospinal Fluid.
Time Frame: Part1: Baseline, 4 week Part2: Baseline, 12 week
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Part1: Baseline, 4 week Part2: Baseline, 12 week
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Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid
Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Change From Baseline in Heparan Sulfate Levels in Serum
Time Frame: Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Change From Baseline in Heparan Sulfate Levels in Urinary
Time Frame: Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid
Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Change From Baseline in Dermatan Sulfate Levels in Serum
Time Frame: Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Change From Baseline in Dermatan Sulfate Levels in Urinary
Time Frame: Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
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Change From Baseline Opening pressure in Cerebrospinal Fluid
Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Part 1: Baseline, 4 week Part 2: Baseline, 12 week
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Change From Baseline in Liver Volume.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Spleen Volume.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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left ventricular posterior wall thickness
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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interventricular septal thickness
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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left ventricular mass index
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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left ventricular fractional shortening
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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left ventricular ejection fraction
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in Echocardiography.
Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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E/A ratio
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Part 1: Baseline, 5 week Part 2: Baseline, 13 week
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Change From Baseline in 6-minute Walk Test Distance.
Time Frame: Part 2: Baseline, 13 week
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Part 2: Baseline, 13 week
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Change From Baseline in BVMT-R
Time Frame: Part 2: Baseline, 13 week
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Part 2: Baseline, 13 week
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Change From Baseline in HVLT-R
Time Frame: Part 2: Baseline, 13 week
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Part 2: Baseline, 13 week
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Change From Baseline in T.O.V.A.
Time Frame: Part 2: Baseline, 13 week
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Part 2: Baseline, 13 week
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Change From Baseline in PedsQL-FIM
Time Frame: Part 2: Baseline, 13 week
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Part 2: Baseline, 13 week
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
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 (Estimate)
December 14, 2022
Last Update Submitted That Met QC Criteria
December 12, 2022
Last Verified
December 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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