A Study of JR-171 in Patients With Mucopolysaccharidosis I

Mucopolysaccharidosis I Clinical Trial

Official title:

Phase I/II Study of JR-171 ㏌ Patients With Mucopolysaccharidosis Type I

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04227600
• Other study ID #: JR-171-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 1, 2020
• Est. completion date: August 2, 2022

Study information

• Verified date: December 2022
• Source: JCR Pharmaceuticals Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 2, 2022
• Est. primary completion date: August 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis I

Intervention

Drug:
• JR-171 (lepunafusp alfa)
IV infusion

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Instituto de Genética e Erros Inatos do Metabolismo - IGEIM	São Paulo
Japan	Fukuoka Children's Hospital	Fukuoka
Japan	Kochi Medical School Hospital	Nankoku
Japan	Osaka Metropolitan University Hospital	Osaka
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
JCR Pharmaceuticals Co., Ltd.

Countries where clinical trial is conducted

United States,  Brazil,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events	Adverse events	13 Week
Primary	Number of participants with Adverse Events	Laboratory tests (hematology, biochemistry, serum iron tests, and urinalysis)	13 Week
Primary	Number of participants with Adverse Events	Vital signs (pulse rate, body temperature, blood pressure, respiratory rate and percutaneous oxygen saturation)	13 Week
Primary	Number of participants with Adverse Events	12-lead electrocardiogram	13 Week
Primary	Number of participants with Adverse Events	Antibodies [anti-human-a-L-iduronidase (anti-IDUA) and anti-JR-171 antibodies]	13 Week
Primary	Number of participants with Adverse Events	Infusion associated reaction (IAR)	13 Week
Secondary	Assessment of plasma drug concentration		Part1: 1,2,3,4 week, Part2: 1,4,12 week
Secondary	Assessment of pharmacokinetic parameter	Maximum Plasma Concentration[Cmax]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Area Under the Curve from time zero to the last blood sampling time point[AUC0-t]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Area Under the Curve from time zero to infinity [AUC0-8]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Time to reach maximum plasma concentration [tmax]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Elimination half-life [t1/2]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Elimination rate constant [kel]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Assessment of pharmacokinetic parameter	Mean residence time from time zero to the last blood sampling time point [MRT0-t]	Part1: 1,2,3,4 week, Part2: 1, 4, 12 week
Secondary	Change From Baseline Drug concentration in Cerebrospinal Fluid.		Part1: Baseline, 4 week Part2: Baseline, 12 week
Secondary	Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid		Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Secondary	Change From Baseline in Heparan Sulfate Levels in Serum		Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Secondary	Change From Baseline in Heparan Sulfate Levels in Urinary		Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Secondary	Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid		Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Secondary	Change From Baseline in Dermatan Sulfate Levels in Serum		Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Secondary	Change From Baseline in Dermatan Sulfate Levels in Urinary		Part 1: Baseline, 2,3,4,5 week Part2: Baseline, 2, 4, 6, 8, 10, 12, 13 week
Secondary	Change From Baseline Opening pressure in Cerebrospinal Fluid		Part 1: Baseline, 4 week Part 2: Baseline, 12 week
Secondary	Change From Baseline in Liver Volume.		Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Spleen Volume.		Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	left ventricular posterior wall thickness	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	interventricular septal thickness	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	left ventricular mass index	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	left ventricular fractional shortening	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	left ventricular ejection fraction	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in Echocardiography.	E/A ratio	Part 1: Baseline, 5 week Part 2: Baseline, 13 week
Secondary	Change From Baseline in 6-minute Walk Test Distance.		Part 2: Baseline, 13 week
Secondary	Change From Baseline in BVMT-R		Part 2: Baseline, 13 week
Secondary	Change From Baseline in HVLT-R		Part 2: Baseline, 13 week
Secondary	Change From Baseline in T.O.V.A.		Part 2: Baseline, 13 week
Secondary	Change From Baseline in PedsQL-FIM		Part 2: Baseline, 13 week