cebsulfase alfa for Metachromatic leukodystrophy | Late infantile metachromatic leukodystrophy

Inclusion criteria

• {"criterion_text":"- 01. 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\n- 02. 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.\n- 03. 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\n- 04. 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 GMFCMLD 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\n- 05. The subject and his/her parent/representative(s) must have the ability to comply with the clinical protocol.\n- 06. 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."}

Exclusion criteria

• {"criterion_text":"- 01. 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\n- 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-APORT 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\n- 02. 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\n- 03. 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.\n- 04. The subject has any known or suspected hypersensitivity to agents used for anesthesia or has history of difficult airway or potential for airway compromise\n- 05. Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study\n- 06. 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.\n- 07. The subject is enrolled in another clinical study that involves use of any investigational product (drug or device) within 30 days or 5 halflives (whichever is longer) prior to study enrollment or at any time during the study\n- 08. The subject has had prior exposure to SHP611\n- 09. The subject must weight > 11lbs (5kg)"}

Primary endpoints

• {"endpoint_text":"- 01. 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.","definition_or_measurement_approach":"Time to loss of locomotion measured by progression to GMFC-MLD category 5 or higher, or death, whichever occurs first, assessed up to Week 106 in subjects in Group A (measured using the Gross Motor Function Classification in Metachromatic Leukodystrophy scale)."}

Secondary endpoints

• {"endpoint_text":"- 01. 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","definition_or_measurement_approach":"Response = maintenance of gross motor function at Week 106; subjects who do not experience progression to GMFC-MLD category 5 or higher or death within Week 106 are considered responders."}
• {"endpoint_text":"- 02. 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","definition_or_measurement_approach":"Change from baseline in GMFC-MLD at Week 106 and EOS; proportion of subjects with unreversed decline >2 categories (not reverted to ≤2-category decline by Week 106)."}
• {"endpoint_text":"- 02. Decline in gross motor function using GMFC MLD: - 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","definition_or_measurement_approach":"Time to unreversed decline from baseline in GMFC-MLD of >2 categories (defined as decline that has not reverted to a 2-category decline or better by last recorded observation)."}
• {"endpoint_text":"- 03. Change from baseline at Week 106 and EOS in CSF sulfatides levels","definition_or_measurement_approach":"Change from baseline in cerebrospinal fluid (CSF) sulfatides levels measured at Week 106 and End of Study (pharmacodynamic biomarker assessment)."}
• {"endpoint_text":"- 04. Response in Group A, defined as maintenance of gross motor function at Week 106, defined as a GMFM 88 total score ≥40","definition_or_measurement_approach":"Response defined as GMFM-88 total score ≥40 at Week 106 indicating maintenance of gross motor function."}
• {"endpoint_text":"- 05. 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","definition_or_measurement_approach":"Time to unreversed decline in GMFM-88 total score defined as either a decrease >20 points from baseline or unreversed decline to a score <40, assessed up to Week 106 and EOS."}
• {"endpoint_text":"- 05. Decline in gross motor function using GMFM-88: - 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","definition_or_measurement_approach":"Change from baseline in GMFM-88 total score at Week 106 and EOS; subgroup of subjects with ≤20-point decrease from baseline and total score ≥40 at Week 106 and EOS."}
• {"endpoint_text":"- 06. Change from baseline at Week 106 and EOS in expressive language using the ELFC-MLD","definition_or_measurement_approach":"Change from baseline in expressive language assessed by ELFC-MLD at Week 106 and End of Study."}

Greece

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

20-09-2024

Processing Time Days

17

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

29-10-2024

Processing Time Days

56

Number Of Sites

1

Number Of Participants

1

Belgium

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

20

Number Of Sites

2

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

26-09-2024

Processing Time Days

23

Number Of Sites

2

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

18-09-2024

Processing Time Days

15

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Shire Human Genetic Therapies Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

Operational study management, monitoring, regulatory and DSMB related responsibilities (multiple codes listed)

Name

PPD Global Ltd.

Responsibilities

Project management duties and monitoring/regulatory

Name

Pharmaceutical Product Development LLC

Responsibilities

Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Serology/endocrinology

Third parties

• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"\"Serum and CSF for Ab, Serum and CSF for PK, PBMC for CRIM\"","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"biomarkers, Urine Sulfatides / Creatinine","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"ePRO tabs, IVRS - treatment randomisation","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Multiple operational and oversight roles including DSMB and various study operational functions (codes listed in dossier)","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"Project management duties and monitoring/regulatory","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"biomarkers, Urine Sulfatides / Creatinine","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenwood Genetic Center Inc.","duties_or_roles":"ASA Activity and Genotyping","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"MRI and MRS services","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Rare Disease Research Partners Limited","duties_or_roles":"patient travel arrangements and reimbursement","organisation_type":"Patient organisation/association"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Serum and CSF for Ab, Serum and CSF for PK, PBMC for CRIM","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"patient travel arrangements and reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Serology/ endocrinology","organisation_type":"Pharmaceutical company"}