A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy

NCT03771898 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: SHP611-2012018-003291-12jRCT2041200086
• Study Type: interventional
• Target: 36
• Locations: 14 countries
• Sites: 30

Brief Summary

The main aim of the study is to determine if SHP611 given by injection into the spinal fluid that surrounds the brain and spinal cord (intrathecal; IT) prolongs the time for children with Metachromatic Leukodystrophy (MLD) to retain the ability to move from place to place. Other aims of the study are to determine the effects of intrathecal administration of SHP611 on movement and speech functions and to learn how well SHP611 injected in the spinal fluid that surrounds the brain and spinal cord is tolerated. Study participants will receive SHP611 for about 2 years with the possibility of an extended treatment period.

Conditions

Metachromatic Leukodystrophy (MLD)

Outcome Measures

Primary Outcomes (1)

• Percent Probability of Free of Loss of Locomotion in the Last Time Interval Up to 2 Years (Week 106) Based on GMFC-MLD for SHP611 Group A and GLIA-MLD Matched External Control

  Loss of locomotion was estimated using interval censoring survival analysis. Survival probability free of loss of locomotion based on GMFC-MLD was estimated up to Week 106 (or two years), with associated 2-sided 95 percent (%) confidence interval (CI). GMFC-MLD scale consists of 7 categories, scores ranging from 0 (walking without support with quality of performance normal for age) to 6 (loss of any locomotion as well as loss of any head and trunk control). Higher scores mean a worse outcome. The data was reported in terms of Mean as survival function was quantified using a weighted average of percentage of participants not reaching the event of interest, with weights derived from the relative size of treated and control units in the strata used for the stratified log-rank test in the primary analysis.

  Baseline up to Week 106

Secondary Outcomes (21)

• Group A: Number of Participants Who Maintained Their Gross Motor Function Evaluated by Using the GMFC-MLD at Week 106 Compared With Matched External Control Group Data

  Baseline up to Week 106

• Number of Participants With Change From Baseline in Gross Motor Function Evaluated by Using the GMFC-MLD at Week 106

  Baseline, Week 106

• Group A: Number of Participants With Decline From Baseline in GMFC-LMD of More Than 2 Categories

  Baseline, Week 106

• Group A: Time to Decline From Baseline in GMFC-MLD of More Than 2 Categories

  Baseline, Week 106

• Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatides Levels at Week 106

  Baseline, Week 106

Study Arms (1)

SHP611

EXPERIMENTAL

Participants will receive 150 milligrams (mg) of SHP611 intrathecally (IT) via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once weekly for 106 weeks in six groups (Group A, B, C, D, E, and F) based on participant's age and motor dysfunction.

Drug: SHP611

Interventions

SHP611 DRUG

Participants will receive 150 mg of SHP611 IT via IDDD or LP once weekly for 106 weeks.

Also known as: HGT-1110, TAK-611, recombinant human arylsulfatase A [rhASA]

SHP611

Eligibility Criteria

• Age: 6 Months - 72 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The participant must have a documented diagnosis of MLD (Groups A-F):
• Low ASA activity in leukocytes (compared to laboratory normal range).
• Elevated sulfatides in urine.
• The participant 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 greater than or equal to (\> =) 6 to less than (\<) 18 months of age (Group D) or be early symptomatic and \> =12 to \< 18 months of age (Group E). Participants in Group E must have neurological symptoms either documented by either a primary care physician or a specialist physician.
• The participant'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.
• The participant'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, \>= 6 to \< 18 months of age, with the same arylsulfatase (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 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.
• The participant and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
• Participant'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 participant.

You may not qualify if:

• 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.
• 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.
• The participant has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise.
• Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study.
• Participants 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.
• The participant 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.
• The participant has had prior exposure to SHP611.
• The participants must weigh \> 11 pound (lbs) (5 kilograms \[kg\]).
• The participant has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use (IFU)
• The participant has had, or may have, an allergic reaction to the materials of construction.
• The participant has shown an intolerance to an implanted device.
• The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port.
• The participant's drug therapy requires substances known to be incompatible with the materials of construction.
• The participant has a known or suspected local or general infection.
• The participant is at risk of abnormal bleeding due to a medical condition or therapy.

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (30)

Los Angeles Biomedical Research Institute at Harbor-UCLA

Torrance, California, 90502, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30303, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Hospital Universitario Austral - PIN

Ciudad Autónoma Buenos Aires, Buenos Aires, B1629AHJ, Argentina

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hôpital Bicêtre - Paris Sud

Le Kremlin-Bicêtre, 94275, France

Location

CHU Lenval

Nice, 06200, France

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Attikon University General Hospital

Chaïdári, Attica, 124 62, Greece

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

IRCCS Ospedale Pediatrico Bambino Gesù - INCIPIT - PIN

Roma, 165, Italy

Location

Kanazawa University Hospital

Kanazawa, 920-8641, Japan

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Vall d'Hebrón

Barcelona, 8035, Spain

Location

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Leukodystrophy, Metachromatic

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 11, 2018
• Study Start: May 13, 2019
• Primary Completion: March 8, 2023
• Study Completion: May 1, 2026
• Last Updated: April 15, 2026
• Results First Posted: June 6, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement

Locations

GR (1); BR (1); CA (4); FR (2); IT (1); GB (1); DE (2); US (11); NL (1); ES (2); BE (1); AR (1); IL (1); JP (1)