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Trial record 1 of 1 for:    NCT04227600
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A Study of JR-171 in Patients With Mucopolysaccharidosis I

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ClinicalTrials.gov Identifier: NCT04227600
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
JCR Pharmaceuticals Co., Ltd.

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).

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis I Drug: JR-171 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of JR-171 ㏌ Patients With Mucopolysaccharidosis Type I
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : May 31, 2022


Arm Intervention/treatment
Experimental: Part1 JR-171
Drug: JR-171 IV infusion, dose escalation
Drug: JR-171
IV infusion

Experimental: Part2 JR-171
Drug: JR-171 IV infusion, dose escalation, low dose, high dose
Drug: JR-171
IV infusion




Primary Outcome Measures :
  1. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    Adverse events

  2. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    Laboratory tests (hematology, biochemistry, serum iron tests, and urinalysis)

  3. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    Vital signs (pulse rate, body temperature, blood pressure, respiratory rate and percutaneous oxygen saturation)

  4. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    12-lead electrocardiogram

  5. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    Antibodies [anti-human-α-L-iduronidase (anti-IDUA) and anti-JR-171 antibodies]

  6. Number of participants with Adverse Events [ Time Frame: 13 Week ]
    Infusion associated reaction (IAR)


Secondary Outcome Measures :
  1. Assessment of plasma drug concentration [ Time Frame: Part1: 1,2,3,4 week, Part2: 1,4,12 week ]
  2. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Maximum Plasma Concentration[Cmax]

  3. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Area Under the Curve from time zero to the last blood sampling time point[AUC0-t]

  4. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Area Under the Curve from time zero to infinity [AUC0-∞]

  5. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Time to reach maximum plasma concentration [tmax]

  6. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Elimination half-life [t1/2]

  7. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Elimination rate constant [kel]

  8. Assessment of pharmacokinetic parameter [ Time Frame: Part1: 1,2,3,4 week, Part2: 1, 4, 12 week ]
    Mean residence time from time zero to the last blood sampling time point [MRT0-t]

  9. Change From Baseline Drug concentration in Cerebrospinal Fluid. [ Time Frame: Part1: Baseline, 4 week Part2: Baseline, 12 week ]
  10. Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week ]
  11. 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 ]
  12. 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 ]
  13. Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week ]
  14. 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 ]
  15. 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 ]
  16. Change From Baseline Opening pressure in Cerebrospinal Fluid [ Time Frame: Part 1: Baseline, 4 week Part 2: Baseline, 12 week ]
  17. Change From Baseline in Liver Volume. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
  18. Change From Baseline in Spleen Volume. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
  19. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    left ventricular posterior wall thickness

  20. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    interventricular septal thickness

  21. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    left ventricular mass index

  22. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    left ventricular fractional shortening

  23. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    left ventricular ejection fraction

  24. Change From Baseline in Echocardiography. [ Time Frame: Part 1: Baseline, 5 week Part 2: Baseline, 13 week ]
    E/A ratio

  25. Change From Baseline in 6-minute Walk Test Distance. [ Time Frame: Part 2: Baseline, 13 week ]
  26. Change From Baseline in BVMT-R [ Time Frame: Part 2: Baseline, 13 week ]
  27. Change From Baseline in HVLT-R [ Time Frame: Part 2: Baseline, 13 week ]
  28. Change From Baseline in T.O.V.A. [ Time Frame: Part 2: Baseline, 13 week ]
  29. Change From Baseline in PedsQL-FIM [ Time Frame: Part 2: Baseline, 13 week ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04227600


Contacts
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Contact: JCR Pharmaceuticals Co., Ltd. +81-(0)797-32-8582 kaihatsu@jcrpharm.co.jp

Locations
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Brazil
Hospital de Clínicas de Porto Alegre Recruiting
Porto Alegre, Brazil
Contact: Roberto Giugliani    +5551-3359-6340      
Instituto de Genética e Erros Inatos do Metabolismo - IGEIM Recruiting
São Paulo, Brazil
Contact: Ana Maria Martins    +5511-5081-9620      
Japan
Fukuoka Children's Hospital Recruiting
Fukuoka, Japan
Contact: Ryutaro Kira    +81-92-682-7000      
Kochi Medical School Hospital Active, not recruiting
Nankoku, Japan
Osaka City University Hospital Recruiting
Osaka, Japan
Contact: Takashi Hamazaki    +81-6-6645-2121      
Sponsors and Collaborators
JCR Pharmaceuticals Co., Ltd.
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Responsible Party: JCR Pharmaceuticals Co., Ltd.
ClinicalTrials.gov Identifier: NCT04227600    
Other Study ID Numbers: JR-171-101
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mucopolysaccharidoses
Mucopolysaccharidosis I
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases