Treatment of Metachromatic Leukodystrophy MedDRA version: 20.0 Level: PT Classification code 10067609 Term: Metachromatic leukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: SHP611
Pharmaceutical Form: Solution for injection
INN or Proposed INN: cebsulfase alfa
Current Sponsor code: SHP611
Other descriptive name: rhASA [recombinant human arylsulfatase A], fo
Sponsors
Shire Human Genetics Therapies Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient has participated in Study HGT-MLD-070 through Week 40. 2. Patient must have no safety or medical issues that contraindicate participation 3. The patient, patient’s parent(s) or legally authorized representative(s) must provide written informed consent and/or assent (if applicable) prior to performing any study-related activities. Are the trial subjects under 18? yes Number of subjects for this age range: 24 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
Exclusion criteria: 1.The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator. 2.Undergoes bone marrow transplantation, hematopoietic stem cell transplantation, or gene therapy at any point during the study. 3.The patient has any known or suspected hypersensitivity to agents used for anesthesia or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions. 4.The patient is pregnant or breastfeeding. 5.The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or drug delivery device) other than those used in HGT-MLD-070 within 6 months prior to study enrollment or at any time during the study. 6.The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including: a. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device b. The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator c. The patient has a known or suspected local or general infection d. The patient is at risk of abnormal bleeding due to a medical condition or therapy e. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation f. The patient has a functioning CSF shunt device g. The patient has shown intolerance to an implanted device
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To collect long-term safety data in patients with MLD who are receiving HGT-1110 and have participated in study HGT-MLD-070 through Week 40.;Secondary Objective: - To evaluate the effects of IT administration of HGT-1110 on gross motor function - To evaluate the effect of IT administration of HGT-1110 on adaptive behavior; as of 12 October 2021, Vineland Adaptive Behavior Scales, Second Edition (VABS-II) will not be collected - To evaluate the effect of IT administration of HGT-1110 on health status and the ability to carry out activities of daily life - To assess repeated-dose pharmacokinetics of HGT-1110 in serum - To assess concentrations of HGT-1110 in cerebrospinal fluid (CSF) ;Primary end point(s): Safety will be measured by the following endpoints: - Reporting of treatment-emergent adverse events - Change from baseline in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis) - Change from baseline in vital signs, physical examinations, and CSF chemistries (including cell counts, glucose, albumin, and protein); as of 15 March 2022, CSF albumin will not be collected - Determination of the presence of anti-HGT-1110 antibodies in CSF and/or serum ;Timepoint(s) of evaluation of this end point: - Adverse events, vital signs, physical examinations, and CSF chemistries are checked every other week - Change from baseline in clinical laboratory testing and determination of the presence of anti-HGT-1110 antibodies at quaterly visits (weeks 52, 66, 78, 92 and 104) and biannually hereafter (weeks 130, 156, 182, 208, 234, 260, 286, 312, 338, 364, 390, 416, 442, 468, 494, 520, 546, 572, 598 and 624) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: - Change from baseline at end of study in motor function using the Gross Motor Function Measure-88 (GMFM-88) total score; the motor function assessments (GMFM-88, global impression of motor function-change [GIMF-C], and global impression of motor function-severity [GIMF-S]) will no longer be collected when patients reach Gross Motor Function Classification System (GMFCS) level 5 - Change from baseline at end of study in the adaptive behavior composite standard score as measured by the VABS II; as of 12 October 2021, VABS-II will not be collected - Change from baseline at end of study in the domain-specific Caregiver Observed MLD Functioning and Outcomes Reporting Tool (COMFORT) scores - Repeated-dose pharmacokinetic parameter estimates for HGT-1110 in serum - Concentrations of HGT-1110 in CSF at selected time points after repeated investigational drug product administration;Timepoint(s) of evaluation of this end point: Efficacy outcome assessments will be performed quarterly from Week 40 through Week 104 at Weeks 52, 66, 78, 92, 104, 130, 156, 182, 208, 234, 260, 286, 312, 338, 364, 390, 416, 442, 468, 494, 520, 546, 572, 598 and 624. These efficacy outcome assessments are the GMFM-88, GIMF-C, GIMF-S, the VABS-II, the COMFORT questionnaire, sample collection for biomarker assessments (serum, CSF, and urine). | — |
Countries
Brazil, Czechia, Czech Republic, Denmark, France, Germany, Italy, Japan, United Kingdom
Contacts
Public ContactDavid Whiteman
Takeda Pharmaceutical Company Limited
Outcome results
None listed