A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)

A Global Phase III multicenter, randomized, assessor-blinded, active-controlled designed to evaluate safety and efficacy of study drug for the treatment of the MPS II.

Study Overview

• Status: Recruiting
• Conditions: Mucopolysaccharidosis II
• Intervention / Treatment: Drug: JR-141; Drug: Idursulfase; Drug: JR-141 or Idursulfase

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: JCR Pharmaceuticals Co., Ltd.; Phone Number: +81-(0)797-32-8582; Email: clinical_development@jp.jcrpharm.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Recruiting
    • Hospital Universitario Austral
    • Contact: Hernán M Amartino; Phone Number: +541158239252
• Brazil
  • Porto Alegre, Brazil
    • Recruiting
    • Hospital de Clinicas de Porto Alegre
    • Contact: Roberto Giugliani
    • Contact: Phone Number: +5551-3359-6340
  • Recife, Brazil
    • Recruiting
    • Instituto de Medicina Integral Prof. Fernando Figueira - Imip
    • Contact: Ana C Menezes; Phone Number: +55 81 2122-4792
  • São Paulo, Brazil
    • Recruiting
    • Instituto de Genética e Erros Inatos do Metabolismo
    • Contact: Ana Maria Martins
    • Contact: Phone Number: +5511-5081-9620
• France
  • Bron cedex, France
    • Recruiting
    • Hôpital Femme Mère Enfant
    • Contact: Nathalie Guffon
    • Contact: Phone Number: +33-825-08-25-69
  • Montpellier, France
    • Recruiting
    • Chu De Montpellier Hopital Gui De Chauliac
    • Contact: Agathe Roubertie; Phone Number: +33 467 336733
  • Paris, France
    • Recruiting
    • Hopital Armand Trousseau
    • Contact: Benedicte Héron-Longe; Phone Number: +33 1 44 73 74 75
• Germany
  • Giessen, Germany
    • Recruiting
    • Universitätsklinikum Gießen
    • Contact: Christina Lampe; Phone Number: +49 641 985 52908
  • Hamburg, Germany
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
    • Contact: Nichole Muschol
    • Contact: Phone Number: +49 40 74100
  • Hochheim, Germany
    • Recruiting
    • SphinCS GmbH
    • Contact: Eugen Mengel
    • Contact: Phone Number: +49-6146-904820
  • Mainz, Germany
    • Recruiting
    • Universitätsmedizin Mainz
    • Contact: Julia Hennermann
    • Contact: Phone Number: +49 6131 17 0
• Italy
  • Rome, Italy
    • Recruiting
    • Osp. Pediatrico Bambino Gesù, IRCCS
    • Contact: Federica Deodato; Phone Number: +39 668592275
• Poland
  • Kraków, Poland
    • Recruiting
    • Uniwersytecki Szpital Dzieciecy
    • Contact: Przemk Kwinta; Phone Number: 48126582011
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Joan de Deu
    • Contact: Mar O'Callaghan
    • Contact: Phone Number: +34-93-600-97-83
• Turkey
  • Ankara, Turkey
    • Recruiting
    • Gazi University Medicine Faculty Hospital
    • Contact: Fatih S Ezgu; Phone Number: +905372653249
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital for Children NHS Trust - Metabolic Medicine
    • Contact: James Davison; Phone Number: +44 20 7405 9200
• United States
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
      • Contact: Paul Harmatz
      • Contact: Phone Number: +1-510-428-3058
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Contact: Barbara Burton
      • Contact: Phone Number: 312-227-6120
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Chester B. Whitley
      • Contact: Phone Number: +1 612-625-1594
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7487
      • Recruiting
      • University of North Carolina at Chapel Hill Medical School Wing E
      • Contact: Elizabeth Jalazo, Dr.; Phone Number: 919-962-8463; Email: veronica_lippuner@med.unc.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Can Ficicioglu
      • Contact: Phone Number: +1-800-879-2467

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A patient who voluntarily signs an Institutional Review Board or Independent Ethics Committee-approved written informed consent form. If the patient is aged under 18 years (aged under 16 years in the UK) at the time of enrollment or willingness to participate in the study cannot be confirmed due to MPS II-related intellectual disability, the patient's legally acceptable representative (e.g., his/her parents or guardians) may sign the informed consent on behalf of the patient. Written informed assent should be obtained from the patient, wherever possible.
• Patients with confirmed diagnosis of MPS II
• Naïve patients or patients who are receiving stable enzyme replacement therapy with idursulfase for more than 12 weeks before starting administration of JR-141 or idursulfase for this study.
• Patients or patients whose partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception being use of condoms from the time of informed consent.

<Cohort A>

• Patients aged 36-42 months old at the time of ICF signing: patients must have a standard score measured by the BSID-III of 85 or less at screening.
• Patients aged 43-71 months old at the time of ICF signing: patients must EITHER have (1) A DQ measured by BSID-III of 20 to 85 at screening OR (2) A composite standard score on NVI measured by KABC-II of 85 or less at screening (only who can perform KABC-II)
• Patients aged 30-35 months old at the time of randomization and who are judged as having the severe phenotype by the Expert Board.

<Cohort B>

• Patients 6 years of age or older at the time of ICF signing and whose IQ are 70 and higher.
• Enrollment of subjects in Cohort B is contingent on the availability in that country of a validated country-specific version of the test (either WISC-V, WAIS-IV, or T.O.V.A.).
• Attenuated patients with 1 SD deficiency in the omission errors or variability domains of the T.O.V.A..

Exclusion Criteria:

• A patient with a history of HSCT with successful engraftment.
• A patient who has received gene therapy treatment at any point.
• Unable to undergo lumbar puncture.
• A patient who is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 4 months before obtaining informed consent.
• Unable to comply with the protocol as determined by the principal investigator or subinvestigator.
• Judged by the principal investigator or subinvestigator to be ineligible to participate in the study due to a history of serious drug allergy or sensitivity including anesthesia or hypersensitivity to any component of JR-141.
• A patient who has a known or suspected local or general infection or is at risk of abnormal bleeding due to medical conditions or therapies.
• A patient who has documented mutation of other genes, including loci adjacent to the IDS gene that are known to be associated with developmental delay, seizures, or other significant CNS disorders.
• A patient who has documented loss of activity of sulfatases other than IDS.
• A patient who has had a ventriculoperitoneal shunt placed or any other brain surgery, or has a clinically significant ventriculoperitoneal shunt malfunction within 30 days of screening.
• full time employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members.
• A patient who otherwise is judged by the principle investigator or sub-investigator to be ineligible to participate in the study.

[Only in France]

• Persons deprived of their liberty by a judicial or administrative decision, according to article L.1121-6 the Public Health Code (Code de la santé publique), adults who are the subject of a measure of legal protection or unable to express their consent according to article L. 1121-8 of the Code de la santé publique)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

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, 2.0 mg/kg/week
Other: administered as the standard of care: idursulfase (ELAPRASE®); standard of care-controlled study	Drug: Idursulfase; IV infusion
Other: Rescue arm	Drug: JR-141 or Idursulfase; The subjects who have achieved the pre-specified criteria* are able to change the drug. *If a subject in Idursulfase group shows decline in their neurocognitive outcome, idursulfase can be switched to JR-141. If a subject in JR-141 group shows decline in their peripheral outcome, JR-141 will be switched to idursulfase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in levels of cerebrospinal fluid heparan sulfate from baseline (Cohort A)	Baseline to Week 53
Change in the raw scores of cognitive testing measured from baseline (BSID-III) (Cohort A)	Baseline to Week 105

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in the growth scores of cognitive testing measured from baseline (BSID-III) (Cohort A)	Baseline to Week 105
Change in the age equivalent scores of adaptive behavior measured from baseline (VABS-II) (Cohort A)	Baseline to Week 105
Relative change in liver volume relative to body weight from baseline (Cohort A and Cohort B)	Baseline to Week 53
Relative change in spleen volume relative to body weight from baseline (Cohort A and Cohort B)	Baseline to Week 53
Relative change in distance walked using the 6-minute walk test from baseline to Week 53 (Cohort B)	Baseline to Week 53

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in levels of cerebrospinal fluid heparan sulfate from baseline. (Cohort A)		Baseline to Week 26, 105
Change in levels of cerebrospinal fluid dermatan sulfate from baseline. (Cohort A)		Baseline to Week 26, 53, 105
Change in levels of cerebrospinal fluid heparan sulfate from baseine. (Cohort B)		Baseline to Week 26, 53
Change in levels of cerebrospinal fluid dermatan sulfate from baseline. (Cohort B)		Baseline to Week 26, 53
Change in adaptive behavioral testing measured from baseline	Vineland Adaptive Behavior Scales (Cohort A)	Baseline to Week 26, 53, 78, 105
Change in adaptive behavioral testing measured from baseline	Vineland Adaptive Behavior Scales (Cohort B)	Baseline to Week 26, 53
Change in cognitive testing measured from baseline	BSID-III and KABC-II (Cohort A)	Baseline to Week 26, 53, 78, 105
Change in the standard scores on omission error and variability domain measured by T.O.V.A. or composite scores on Processing speed or Working Memory measured by WISC/WAIS from baseline (Cohort B)		Baseline to Week 26, 53
Change in adaptive behavior measured by VABS-II, and intelligence scale measured by WISC/WAIS from baseline (Cohort B)		Baseline to Week 26, 53
Change in the Quality of Life by HS FOCUS from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the Quality of Life by PedsQL from baseline. (Cohort A)		Baseline to Week 26, 53, 78, 105
Change in the Quality of Life by PedsQL from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the Quality of Life by PedsQL-FIM from baseline. (Cohort A)		Baseline to Week 26, 53, 78, 105
Change in the Quality of Life by PedsQL-FIM from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the Quality of Life by CSHQ from baseline.(Cohort A)		Baseline to Week 26, 53, 78, 105
Change in the Quality of Life by CSHQ from baseline.(Cohort B)		Baseline to Week 26, 53
Change in the global impression of severity and change by CGI from baseline. (Cohort A)		Baseline to Week 26, 53, 78, 105
Change in the global impression of severity and change by CGI from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the global impression of severity and change by PGI from baseline. (Cohort A)		Baseline to Week 26, 53, 78, 105
Change in the global impression of severity and change by PGI from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the Toileting Abilities Survey from baseline. (Cohort A)		Baseline to Week 13, 26, 53, 78, 105
Change in the Toileting Abilities Survey from baseline. (Cohort B)		Baseline to Week 13, 26, 53
Change in Auditory Brainstem Response. (Cohort A)		Baseline to Week 26, 53, 105
Change in Auditory Brainstem Response. (Cohort B)		Baseline to Week 26, 53
Change in cerebrospinal fluid opening pressure. (Cohort A)		Baseline to Week 26, 53, 105
Change in cerebrospinal fluid opening pressure. (Cohort B)		Baseline to Week 26, 53
Relative change in liver volume relative to body weight from baseline (Cohort A)		Baseline to Week 26, 105
Relative change in liver volume relative to body weight from baseline (Cohort B)		Baseline to Week 26
Relative change in spleen volume relative to body weight from baseline (Cohort A)		Baseline to Week 26, 105
Relative change in spleen volume relative to body weight from baseline (Cohort B)		Baseline to Week 26
Relative change in distance walked using the 6-minute walk test from baseline (Cohort B)		Baseline to Week 26
Change in Joint Range of Motion by goniometer from baseline (Cohort A)		Baseline to Week 26, 53, 105
Change in Joint Range of Motion by goniometer from baseline (Cohort B)		Baseline to Week 26, 53
Absolute change in the Forced Vital Capacity from baseline (Cohort B)		Baseline to Week 26, 53
Absolute change in the Forced Expiratory Volume from baseline (Cohort B)		Baseline to Week 26, 53
Absolute change in the percent predicted Forced Vital Capacity from baseline (Cohort B)		Baseline to Week 26, 53
Change in levels of serum heparan sulfate from baseline (Cohort A)		Baseline to Week 13, 26, 53, 78, 105
Change in levels of serum heparan sulfate from baseline (Cohort B)		Baseline to Week 13, 26, 53
Change in levels of serum dermatan sulfate from baseline (Cohort A)		Baseline to Week 13, 26, 53, 78, 105
Change in levels of serum dermatan sulfate from baseline (Cohort B)		Baseline to Week 13, 26, 53
Change in levels of the urine heparan sulfate from baseline. (Cohort A)		Baseline to Week 13, 26, 53, 78, 105
Change in levels of the urine heparan sulfate from baseline. (Cohort B)		Baseline to Week 13, 26, 53
Change in levels of the urine dermatan sulfate from baseline. (Cohort A)		Baseline to Week 13, 26, 53, 78, 105
Change in levels of the urine dermatan sulfate from baseline. (Cohort B)		Baseline to Week 13, 26, 53
Change in the left ventricular mass index (LVMI) from baseline. (Cohort A)		Baseline to Week 26, 53, 105
Change in LVMI from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the interventricular septum thickness (IVST) from baseline. (Cohort A)		Baseline to Week 26, 53, 105
Change in IVST from baseline. (Cohort B)		Baseline to Week 26, 53
Change in the posterior wall thickness (PWT) from baseline. (Cohort A)		Baseline to Week 26, 53, 105
Change in PWT from baseline. (Cohort B)		Baseline to Week 26, 53
Growth velocity (Cohort A)		Week 53, 105
Growth velocity (Cohort B)		Week 53
Ongoing assessment of adverse events.	adverse drug reactions (Cohort A and Cohort B)	Through study period
Antibodies	Plasma: Anti-IDS antibody (Cohort A)	Baseline, Week 105
Antibodies	Plasma: Anti-IDS antibody (Cohort B)	Baseline, Week 53
Antibodies	Plasma: Anti-JR-141 antibody (Cohort A)	Baseline, Week 5, 13, 26, 53, 78,105
Antibodies	Plasma: Anti-JR-141 antibody (Cohort B)	Baseline, Week 5, 13, 26, 53
Antibodies	Cerebrospinal fluid: Anti-JR-141 antibody (Cohort A)	Baseline, Week 26, 53, 105
Antibodies	Cerebrospinal fluid: Anti-JR-141 antibody (Cohort B)	Baseline, Week 26, 53

Collaborators and Investigators

• Sponsor: JCR Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 3, 2024
• Last Verified: March 1, 2023

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-GS31

Drug and device information, study documents

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