Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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3 February 2025 |
Main ID: |
EUCTR2018-003291-12-NL |
Date of registration:
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10/04/2019 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Research study to determine the effects of an investigational drug, SHP611 on patients with with Late Infantile Metachromatic Leukodystrophy (MLD) specially the gross motor function, using the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD.
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Scientific title:
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A Global, Multicenter, Single-arm, Matched External Control Study of Intrathecal SHP611 in Subjects with Late Infantile Metachromatic Leukodystrophy |
Date of first enrolment:
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24/10/2019 |
Target sample size:
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42 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003291-12 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Argentina
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Belgium
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Brazil
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Canada
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France
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Germany
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Greece
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Israel
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Italy
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Japan
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Netherlands
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Spain
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United Kingdom
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United States
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Contacts
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Name:
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David Whiteman
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Address:
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300 Shire Way
MA 02421
Lexington
United States |
Telephone:
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001781 482 9369 |
Email:
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david.whiteman@takeda.com |
Affiliation:
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Shire Human Genetic Therapies, Inc. |
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Name:
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David Whiteman
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Address:
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300 Shire Way
MA 02421
Lexington
United States |
Telephone:
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001781 482 9369 |
Email:
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david.whiteman@takeda.com |
Affiliation:
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Shire Human Genetic Therapies, Inc. |
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Key inclusion & exclusion criteria
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Inclusion criteria: Patients must meet all of the following criteria to be considered eligible for inclusion as a subject in the study:
1. The subject must have a documented diagnosis of MLD (Groups A-F) • Low ASA activity in leukocytes (compared to laboratory normal range) AND • Elevated sulfatides in urine
2. The subject must have a gait disorder due to spastic ataxia or weakness attributable to MLD by the investigator and documented by a primary care physician or a specialist physician by 30 months of age (Groups A-C, and F), or be minimally symptomatic and =6 to <18 months of age (Group D); or be early symptomatic and =12 to <18 months of age (Group E). Subjects in Group E must have neurological symptoms documented by either a primary care physician or a specialist physician.
3. The subject’s age at the time of informed consent, must be: • Group A: 18 to 48 months of age • Group B: 18 to 72 months of age • Group C: 18 to 72 months of age • Group D: =6 to <18 months of age • Group E: =12 to <18 months of age • Group F: 18 to 72 months of age
4. The subject’s GMFC-MLD category at screening must be: • Group A: GMFC-MLD category of 1 or 2 • Group B: GMFC-MLD category of 3 • Group C: GMFC-MLD category of 4 • Group D: minimally symptomatic, and has the same ASA allelic constitution as an older sibling with confirmed late infantile or juvenile onset MLD • Group E: early symptomatic, =12 to <18 months of age with a GMFC-MLD category of 1 or 2, and with a history of achieving stable walking (defined as at least 1 month of independent walking) • Group F: GMFC-MLD category of 5 or 6
5. The subject and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
6. Subject's parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the subject.
Filtering criteria for the selection of the matched external control group will be provided in the Statistical Analysis Plan (SAP). Are the trial subjects under 18? yes Number of subjects for this age range: 42 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria: 1. Multiple sulfatase disorder as determined by abnormal activity of another lysosomal sulfatase (based upon the reference laboratory’s normal range) or a known genetic disorder other than MLD
2. History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy or undergoes BMT, HSCT, or gene therapy at any point during the study
3. Primary presentation of MLD was behavioral or cognitive symptoms (per investigator’s clinical judgment); behavioral symptoms that are secondary to motor deficits (eg: tantrums in response to loss of motor skills) are not exclusionary.
4. The subject has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise
5. Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study
6. Subjects with laboratory, ECG, or vital sign abnormalities reflecting intercurrent illness that may compromise their safety during the trial should not be enrolled. Abnormal laboratory, vital sign and ECG results at screening should be reviewed with the Takeda medical monitor.
7. The subject is enrolled in another clinical study that involves use of any investigational product (drug or device) within 30 days or 5 half-lives (whichever is longer) prior to study enrollment or at any time during the study
8. The subject has had prior exposure to SHP611
9. The subject must weight > 11lbs (5kg)
10. The subject has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use a. The subject has had, or may have, an allergic reaction to the materials of construction b. The subject has shown an intolerance to an implanted device c. The subject’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port d. The subject’s drug therapy requires substances known to be incompatible with the materials of construction e. The subject has a known or suspected local or general infection f. The subject is at risk of abnormal bleeding due to a medical condition or therapy g. The subject has one or more spinal abnormalities that could complicate safe implantation or fixation h. The subject has a functioning CSF shunt device
Filtering criteria for the selection of the matched external control group will be provided in the Statistical Analysis Plan (SAP).
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
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Late Metachromatic Leukodystrophy (MLD) MedDRA version: 20.0
Level: PT
Classification code 10067609
Term: Metachromatic leukodystrophy
System Organ Class: 10010331 - Congenital, familial and genetic disorders
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Intervention(s)
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Product Code: SHP611 Pharmaceutical Form: Solution for injection INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: SHP611 Other descriptive name: RECOMBINANT HUMAN ARYLSULFATASE A Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 30-
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Primary Outcome(s)
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Main Objective: The primary objective of this study is to evaluate the effects of intrathecal (IT) administration of SHP611 on the time to loss of locomotion, as indicated by category 5 or higher in the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with external control group data in children with late infantile MLD.
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Timepoint(s) of evaluation of this end point: 2 years (week 106)
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Primary end point(s): The primary efficacy endpoint is time to loss of locomotion, measured by progression to GMFC-MLD category 5 or higher, or death, whichever occurs first, up to Week 106, evaluated on subjects in Group A.
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Secondary Objective: - To evaluate the effects of IT administration of SHP611 on subjects who experience decline in gross motor function as indicated by GMFC-MLD category 5 or higher, compared with matched external control group data in children with MLD - To evaluate the effects of IT administration of SHP611 on the decline in gross motor function, as measured by an unreversed decline in GMFC-MLD of more than 2 categories compared with matched external control group data in children with MLD, time course of declining gross motor function using the GMFC-MLD, and change from baseline of gross motor function, using the GMFC-MLD - To evaluate the effects of IT administration of SHP611 on cerebrospinal fluid (CSF) sulfatides (pharmacodynamic [PD] biomarker) - To evaluate the effects of IT administration of SHP611 on gross motor function, using the Gross Motor Function Measure 88 (GMFM-88) total score in children with MLD
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Secondary Outcome(s)
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Secondary end point(s): The secondary efficacy endpoints of this study are: • Response in Group A, defined as maintenance of gross motor function at Week 106, evaluated as subjects who do not experience any event within Week 106, where event is defined as a decline in GMFC MLD to category 5 or higher, or death • Decline in gross motor function using GMFC MLD: - Change from baseline at Week 106 and EOS in gross motor function, using the GMFC MLD - Subjects with unreversed decline from baseline in GMFC-MLD of more than 2 categories, defined as any decline of more than 2-categories that has not reverted to a 2-category decline (or better) at Week 106, evaluated on subjects in Group A - Time to unreversed decline from baseline in GMFC-MLD of more than 2 categories, defined as any decline of more than 2-categories that has not reverted to a 2-category decline (or better) as of the last recorded observation • Change from baseline at Week 106 and EOS in CSF sulfatides levels • Response in Group A, defined as maintenance of gross motor function at Week 106, defined as a GMFM 88 total score =40 • Decline in gross motor function using GMFM-88: - Time to unreversed decline from baseline at Week 106 and EOS in GMFM-88 total score decrease of >20 points or unreversed decline to a score <40 points, whichever occurs first - Change from baseline at Week 106 and EOS in gross motor function, using the GMFM-88 total score - Subjects in Group A with GMFM-88 total score decrease of =20 points from baseline and a total score that is =40 at Week 106 and EOS • Change from baseline at Week 106 and EOS in expressive language using the ELFC-MLD
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Timepoint(s) of evaluation of this end point: 2 years and EOS
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Secondary ID(s)
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NCT03771898
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2018-003291-12-FR
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SHP611-201
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Source(s) of Monetary Support
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Shire Human Genetic Therapies, Inc.
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Ethics review
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Status: Approved
Approval date: 24/10/2019
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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