A Study of JR-171 in Patients With Mucopolysaccharidosis I
Primary Purpose
Mucopolysaccharidosis I
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JR-171 (lepunafusp alfa)
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis I
Eligibility Criteria
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.
Sites / Locations
- UCSF Benioff Children's Hospital Oakland
- Hospital de Clínicas de Porto Alegre
- Instituto de Genética e Erros Inatos do Metabolismo - IGEIM
- Fukuoka Children's Hospital
- Kochi Medical School Hospital
- Osaka Metropolitan University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part1 JR-171
Part2 JR-171
Arm Description
Drug: JR-171 IV infusion, dose escalation
Drug: JR-171 IV infusion, dose escalation, low dose, high dose
Outcomes
Primary Outcome Measures
Number of participants with Adverse Events
Adverse events
Number of participants with Adverse Events
Laboratory tests (hematology, biochemistry, serum iron tests, and urinalysis)
Number of participants with Adverse Events
Vital signs (pulse rate, body temperature, blood pressure, respiratory rate and percutaneous oxygen saturation)
Number of participants with Adverse Events
12-lead electrocardiogram
Number of participants with Adverse Events
Antibodies [anti-human-α-L-iduronidase (anti-IDUA) and anti-JR-171 antibodies]
Number of participants with Adverse Events
Infusion associated reaction (IAR)
Secondary Outcome Measures
Assessment of plasma drug concentration
Assessment of pharmacokinetic parameter
Maximum Plasma Concentration[Cmax]
Assessment of pharmacokinetic parameter
Area Under the Curve from time zero to the last blood sampling time point[AUC0-t]
Assessment of pharmacokinetic parameter
Area Under the Curve from time zero to infinity [AUC0-∞]
Assessment of pharmacokinetic parameter
Time to reach maximum plasma concentration [tmax]
Assessment of pharmacokinetic parameter
Elimination half-life [t1/2]
Assessment of pharmacokinetic parameter
Elimination rate constant [kel]
Assessment of pharmacokinetic parameter
Mean residence time from time zero to the last blood sampling time point [MRT0-t]
Change From Baseline Drug concentration in Cerebrospinal Fluid.
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid
Change From Baseline in Heparan Sulfate Levels in Serum
Change From Baseline in Heparan Sulfate Levels in Urinary
Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid
Change From Baseline in Dermatan Sulfate Levels in Serum
Change From Baseline in Dermatan Sulfate Levels in Urinary
Change From Baseline Opening pressure in Cerebrospinal Fluid
Change From Baseline in Liver Volume.
Change From Baseline in Spleen Volume.
Change From Baseline in Echocardiography.
left ventricular posterior wall thickness
Change From Baseline in Echocardiography.
interventricular septal thickness
Change From Baseline in Echocardiography.
left ventricular mass index
Change From Baseline in Echocardiography.
left ventricular fractional shortening
Change From Baseline in Echocardiography.
left ventricular ejection fraction
Change From Baseline in Echocardiography.
E/A ratio
Change From Baseline in 6-minute Walk Test Distance.
Change From Baseline in BVMT-R
Change From Baseline in HVLT-R
Change From Baseline in T.O.V.A.
Change From Baseline in PedsQL-FIM
Full Information
NCT ID
NCT04227600
First Posted
December 27, 2019
Last Updated
December 12, 2022
Sponsor
JCR Pharmaceuticals Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04227600
Brief Title
A Study of JR-171 in Patients With Mucopolysaccharidosis I
Official Title
Phase I/II Study of JR-171 ㏌ Patients With Mucopolysaccharidosis Type I
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
August 2, 2022 (Actual)
Study Completion Date
August 2, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
JCR Pharmaceuticals Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part1 JR-171
Arm Type
Experimental
Arm Description
Drug: JR-171 IV infusion, dose escalation
Arm Title
Part2 JR-171
Arm Type
Experimental
Arm Description
Drug: JR-171 IV infusion, dose escalation, low dose, high dose
Intervention Type
Drug
Intervention Name(s)
JR-171 (lepunafusp alfa)
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Number of participants with Adverse Events
Description
Adverse events
Time Frame
13 Week
Title
Number of participants with Adverse Events
Description
Laboratory tests (hematology, biochemistry, serum iron tests, and urinalysis)
Time Frame
13 Week
Title
Number of participants with Adverse Events
Description
Vital signs (pulse rate, body temperature, blood pressure, respiratory rate and percutaneous oxygen saturation)
Time Frame
13 Week
Title
Number of participants with Adverse Events
Description
12-lead electrocardiogram
Time Frame
13 Week
Title
Number of participants with Adverse Events
Description
Antibodies [anti-human-α-L-iduronidase (anti-IDUA) and anti-JR-171 antibodies]
Time Frame
13 Week
Title
Number of participants with Adverse Events
Description
Infusion associated reaction (IAR)
Time Frame
13 Week
Secondary Outcome Measure Information:
Title
Assessment of plasma drug concentration
Time Frame
Part1: 1,2,3,4 week, Part2: 1,4,12 week
Title
Assessment of pharmacokinetic parameter
Description
Maximum Plasma Concentration[Cmax]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Area Under the Curve from time zero to the last blood sampling time point[AUC0-t]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Area Under the Curve from time zero to infinity [AUC0-∞]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Time to reach maximum plasma concentration [tmax]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Elimination half-life [t1/2]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Elimination rate constant [kel]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Assessment of pharmacokinetic parameter
Description
Mean residence time from time zero to the last blood sampling time point [MRT0-t]
Time Frame
Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Title
Change From Baseline Drug concentration in Cerebrospinal Fluid.
Time Frame
Part1: Baseline, 4 week Part2: Baseline, 12 week
Title
Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid
Time Frame
Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Title
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
Title
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
Title
Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid
Time Frame
Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Title
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
Title
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
Title
Change From Baseline Opening pressure in Cerebrospinal Fluid
Time Frame
Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Title
Change From Baseline in Liver Volume.
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Spleen Volume.
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
left ventricular posterior wall thickness
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
interventricular septal thickness
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
left ventricular mass index
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
left ventricular fractional shortening
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
left ventricular ejection fraction
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in Echocardiography.
Description
E/A ratio
Time Frame
Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Title
Change From Baseline in 6-minute Walk Test Distance.
Time Frame
Part 2: Baseline, 13 week
Title
Change From Baseline in BVMT-R
Time Frame
Part 2: Baseline, 13 week
Title
Change From Baseline in HVLT-R
Time Frame
Part 2: Baseline, 13 week
Title
Change From Baseline in T.O.V.A.
Time Frame
Part 2: Baseline, 13 week
Title
Change From Baseline in PedsQL-FIM
Time Frame
Part 2: Baseline, 13 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
Country
Brazil
Facility Name
Instituto de Genética e Erros Inatos do Metabolismo - IGEIM
City
São Paulo
Country
Brazil
Facility Name
Fukuoka Children's Hospital
City
Fukuoka
Country
Japan
Facility Name
Kochi Medical School Hospital
City
Nankoku
Country
Japan
Facility Name
Osaka Metropolitan University Hospital
City
Osaka
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of JR-171 in Patients With Mucopolysaccharidosis I
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