Clinical trial NCT04573023: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
Official title: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Mucopolysaccharidosis II
Lead sponsor: JCR Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change in levels of cerebrospinal fluid heparan sulfate from baseline (Cohort A)
timeFrame: Baseline to Week 53
measure: Change in the raw scores of cognitive testing measured from baseline (BSID-III) (Cohort A)
timeFrame: Baseline to Week 105
Secondary outcomes:
measure: Change in the growth scores of cognitive testing measured from baseline (BSID-III) (Cohort A)
timeFrame: Baseline to Week 105
measure: Change in the age equivalent scores of adaptive behavior measured from baseline (VABS-II) (Cohort A)
timeFrame: Baseline to Week 105
measure: Relative change in liver volume relative to body weight from baseline (Cohort A and Cohort B)
timeFrame: Baseline to Week 53
measure: Relative change in spleen volume relative to body weight from baseline (Cohort A and Cohort B)
timeFrame: Baseline to Week 53
measure: Relative change in distance walked using the 6-minute walk test from baseline to Week 53 (Cohort B)
timeFrame: Baseline to Week 53
Other outcomes:
measure: Change in levels of cerebrospinal fluid heparan sulfate from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 105
measure: Change in levels of cerebrospinal fluid dermatan sulfate from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in levels of cerebrospinal fluid heparan sulfate from baseine. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in levels of cerebrospinal fluid dermatan sulfate from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in adaptive behavioral testing measured from baseline
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in adaptive behavioral testing measured from baseline
timeFrame: Baseline to Week 26, 53
measure: Change in cognitive testing measured from baseline
timeFrame: Baseline to Week 26, 53, 78, 105
measure: 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)
timeFrame: Baseline to Week 26, 53
measure: Change in adaptive behavior measured by VABS-II, and intelligence scale measured by WISC/WAIS from baseline (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the Quality of Life by HS FOCUS from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the Quality of Life by PedsQL from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in the Quality of Life by PedsQL from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the Quality of Life by PedsQL-FIM from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in the Quality of Life by PedsQL-FIM from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the Quality of Life by CSHQ from baseline.(Cohort A)
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in the Quality of Life by CSHQ from baseline.(Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the global impression of severity and change by CGI from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in the global impression of severity and change by CGI from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the global impression of severity and change by PGI from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 78, 105
measure: Change in the global impression of severity and change by PGI from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the Toileting Abilities Survey from baseline. (Cohort A)
timeFrame: Baseline to Week 13, 26, 53, 78, 105
measure: Change in the Toileting Abilities Survey from baseline. (Cohort B)
timeFrame: Baseline to Week 13, 26, 53
measure: Change in Auditory Brainstem Response. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in Auditory Brainstem Response. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in cerebrospinal fluid opening pressure. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in cerebrospinal fluid opening pressure. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Relative change in liver volume relative to body weight from baseline (Cohort A)
timeFrame: Baseline to Week 26, 105
measure: Relative change in liver volume relative to body weight from baseline (Cohort B)
timeFrame: Baseline to Week 26
measure: Relative change in spleen volume relative to body weight from baseline (Cohort A)
timeFrame: Baseline to Week 26, 105
measure: Relative change in spleen volume relative to body weight from baseline (Cohort B)
timeFrame: Baseline to Week 26
measure: Relative change in distance walked using the 6-minute walk test from baseline (Cohort B)
timeFrame: Baseline to Week 26
measure: Change in Joint Range of Motion by goniometer from baseline (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in Joint Range of Motion by goniometer from baseline (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Absolute change in the Forced Vital Capacity from baseline (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Absolute change in the Forced Expiratory Volume from baseline (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Absolute change in the percent predicted Forced Vital Capacity from baseline (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in levels of serum heparan sulfate from baseline (Cohort A)
timeFrame: Baseline to Week 13, 26, 53, 78, 105
measure: Change in levels of serum heparan sulfate from baseline (Cohort B)
timeFrame: Baseline to Week 13, 26, 53
measure: Change in levels of serum dermatan sulfate from baseline (Cohort A)
timeFrame: Baseline to Week 13, 26, 53, 78, 105
measure: Change in levels of serum dermatan sulfate from baseline (Cohort B)
timeFrame: Baseline to Week 13, 26, 53
measure: Change in levels of the urine heparan sulfate from baseline. (Cohort A)
timeFrame: Baseline to Week 13, 26, 53, 78, 105
measure: Change in levels of the urine heparan sulfate from baseline. (Cohort B)
timeFrame: Baseline to Week 13, 26, 53
measure: Change in levels of the urine dermatan sulfate from baseline. (Cohort A)
timeFrame: Baseline to Week 13, 26, 53, 78, 105
measure: Change in levels of the urine dermatan sulfate from baseline. (Cohort B)
timeFrame: Baseline to Week 13, 26, 53
measure: Change in the left ventricular mass index (LVMI) from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in LVMI from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the interventricular septum thickness (IVST) from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in IVST from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Change in the posterior wall thickness (PWT) from baseline. (Cohort A)
timeFrame: Baseline to Week 26, 53, 105
measure: Change in PWT from baseline. (Cohort B)
timeFrame: Baseline to Week 26, 53
measure: Growth velocity (Cohort A)
timeFrame: Week 53, 105
measure: Growth velocity (Cohort B)
timeFrame: Week 53
measure: Ongoing assessment of adverse events.
timeFrame: Through study period
measure: Antibodies
timeFrame: Baseline, Week 105
measure: Antibodies
timeFrame: Baseline, Week 53
measure: Antibodies
timeFrame: Baseline, Week 5, 13, 26, 53, 78,105
measure: Antibodies
timeFrame: Baseline, Week 5, 13, 26, 53
measure: Antibodies
timeFrame: Baseline, Week 26, 53, 105
measure: Antibodies
timeFrame: Baseline, Week 26, 53
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York City
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill Medical School Wing E
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Prof. Fernando Figueira - Imip
city: São Paulo
country: Brazil
facility: Instituto de Genética e Erros Inatos do Metabolismo
city: Bogotá
country: Colombia
facility: Fundación Cardio Infantil - Instituto de Cardiología
city: Bron cedex
country: France
facility: Hôpital Femme Mère Enfant
city: Montpellier
country: France
facility: Chu De Montpellier Hopital Gui De Chauliac
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hochheim
country: Germany
facility: SphinCS GmbH
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Afula
country: Israel
facility: Ha'Emek Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Rome
country: Italy
facility: Osp. Pediatrico Bambino Gesù, IRCCS
city: Kraków
country: Poland
facility: Uniwersytecki Szpital Dziecięcy
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Ankara
country: Turkey
facility: Gazi University Medicine Faculty Hospital
city: Izmir
country: Turkey
facility: Ege University Children Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust - Metabolic Medicine
Study officials:
References: