A Study of JR-141 in Patients With Mucopolysaccharidosis II

Phase II Study of JR-141 in Patients With Mucopolysaccharidosis II

A Phase II open-label, randomized, parallel group, 2 sites (Brazil), designed to evaluate the safety and efficacy of 3 doses of study drug for the treatment of the MPS II.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis II
• Intervention / Treatment: Drug: JR-141; Drug: JR-141; Drug: JR-141

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil
    • Grupo de Pesquisa Clínica em Genética Médica - HCPA
  • São Paulo, Brazil
    • Igeim - Unifesp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males with confirmed diagnosis of MPS II, based on deficient activity of IDS in leucocytes or fibroblasts and/or pathogenic mutations identified in the IDS gene (if enzyme diagnosis was in dried blood spots or plasma, molecular genetics confirmation is mandatory).

• One of the following age groups:

  1. 0 to 3 years and 11 months old (6 patients, 2 in each dose)
  2. 4 years to 7 years and 11 months old (6 patients, 2 in each dose)
  3. 8 years or older (6 patients, 2 in each dose)
• Capable of providing written consent by himself, unless the patient is under the age of 18 years at the time of informed consent process, or it is not possible to obtain consent from the patient himself due to his intellectual disabilities associated with MPS II.
• In the case of a patient who is under the age of 18 years or from whom it is not possible to obtain consent due to his intellectual disabilities associated with MSP II, he may be included if written consent can be provided by legal representative; however written consent should be obtained from the patient himself too, wherever possible.
• Naïve patients or patients who are receiving enzyme replacement therapy with idursulfase could be included if provided treatment has been stable in the last 6 months and agree to interrupt the treatment at least one week before the first study drug infusion, and agree in suspending this treatment for the duration of the trial.

Exclusion Criteria:

• Refusal to sign the informed consent form.
• Unable to perform the study procedures, except for neurocognitive testing.
• Previous engrafted BMT/HSCT.
• Surgical or other major medical intervention planned to occur before week 26.
• Participation in a clinical trial with an investigational drug in the last 12 months.
• Judged by the investigator or subinvestigator as being unable to undergo lumbar puncture, including those who have difficulties in taking a position for lumber puncture due to joint contracture or those who are likely to experience difficulty breathing during the lumbar puncture process.
• Judged by the investigator or subinvestigator to be ineligible to participate in the study due to a history of a serious drug allergy or sensitivity.
• Otherwise judged by the investigator or subinvestigator to be ineligible to participate in the study out of consideration for the subject safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JR-141 2.0 mg/kg/week	Drug: JR-141; IV infusion (lyophilized powder), 1.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 2.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 4.0 mg/kg/week
Experimental: JR-141 1.0 mg/kg/week	Drug: JR-141; IV infusion (lyophilized powder), 1.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 2.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 4.0 mg/kg/week
Experimental: JR-141 4.0 mg/kg/week	Drug: JR-141; IV infusion (lyophilized powder), 1.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 2.0 mg/kg/week; Drug: JR-141; IV infusion (lyophilized powder), 4.0 mg/kg/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events	Adverse events; Antidrug antibodies; Blood pressures in mmHg; Heart rate in beats/minute; Respiratory rate in breaths/minute; Temperature in °C; Presence or absence of abnormalities for physical examination; Presence or absence of abnormalities for 12-lead electrocardiogram; Routine laboratory tests in blood (hematology, liver function, renal function, iron-related levels) and urine (urinalysis)	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Pharmacokinetic parameter [Maximum Plasma Concentration [Cmax]]	Plasma concentration of JR-141	21 hours after dosing at the first and last infusions
Plasma Pharmacokinetic parameter [Area Under the Curve [AUC]]	Plasma concentration of JR-141	21 hours after dosing at the first and last infusions
Liver and spleen volumes (MRI)		26 weeks
Left ventricular mass by a standard 2-dimensional Doppler echocardiogram		26 weeks
Urinary heparan sulfate concentrations		26 weeks
Urinary dermatan sulfate concentrations		26 weeks
Serum heparan sulfate concentrations		26 weeks
Serum dermatan sulfate concentrations		26 weeks

Collaborators and Investigators

• Sponsor: JCR Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): October 4, 2019
• Study Completion (Actual): October 4, 2019

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidosis II; Mucopolysaccharidoses
• Other Study ID Numbers: JR-141-BR21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No