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

Mucopolysaccharidosis II Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04573023
• Other study ID #: JR-141-GS31
• Status: Recruiting
• Phase: Phase 3
• Start date: February 14, 2022
• Est. completion date: January 31, 2026

Study information

• Verified date: June 2024
• Source: JCR Pharmaceuticals Co., Ltd.
• Contact: JCR Pharmaceuticals Co., Ltd.
• Phone: +81-(0)797-32-8582
• Email: clinical_development[@]jp.jcrpharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Drug:
• JR-141
IV infusion, 2.0 mg/kg/week
• Idursulfase
IV infusion
• 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.

Locations

Country	Name	City	State
Argentina	Hospital Universitario Austral	Buenos Aires
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Instituto de Medicina Integral Prof. Fernando Figueira - Imip	Recife
Brazil	Instituto de Genética e Erros Inatos do Metabolismo	São Paulo
France	Hôpital Femme Mère Enfant	Bron cedex
France	Chu De Montpellier Hopital Gui De Chauliac	Montpellier
France	Hôpital Armand Trousseau	Paris
Germany	Universitätsklinikum Giessen	Giessen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	SphinCS GmbH	Hochheim
Germany	Universitätsmedizin Mainz	Mainz
Italy	Osp. Pediatrico Bambino Gesù, IRCCS	Rome
Poland	Uniwersytecki Szpital Dzieciecy	Kraków
Spain	Hospital Sant Joan de Déu	Barcelona
Turkey	Gazi University Medicine Faculty Hospital	Ankara
United Kingdom	Great Ormond Street Hospital for Children NHS Trust - Metabolic Medicine	London
United States	University of North Carolina at Chapel Hill Medical School Wing E	Chapel Hill	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University	New York	New York
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
JCR Pharmaceuticals Co., Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  France,  Germany,  Italy,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

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