A safety and efficacy extension of study HGT-MLD-070 in Children with Metachromatic Leukodystrophy recieving enzyme (HGT-1110) replacement by intrathecal injection

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2012-003775-20-IT
• Date of registration: 15/03/2017
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetics Therapies Inc
• Public title: A safety and efficacy extension of study HGT-MLD-070 in Children with Metachromatic Leukodystrophy recieving enzyme (HGT-1110) replacement by intrathecal injection
• Scientific title: An Open-label Extension of Study HGT-MLD-070 Evaluating Long Term Safety and Efficacy of Intrathecal Administration of HGT-1110 in Patients with Metachromatic Leukodystrophy
• Date of first enrolment: 20/03/2017
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003775-20
• Study type: Interventional clinical trial of medicinal product
• Study design: 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 Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Czech Republic, Denmark, France, Germany, Italy, Japan, United Kingdom

Contacts

• Name: Melanie Ivarsson
• Affiliation: Shire Human Genetic Therapies Inc.

• Name: Melanie Ivarsson
• Affiliation: Shire Human Genetic Therapies Inc.

Key inclusion & exclusion 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:
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.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.
3.The patient is pregnant or breastfeeding.
4.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.
5. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device
6. 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
7. The patient has a known or suspected local or general infection
8. The patient is at risk of abnormal bleeding due to a medical condition or therapy
9. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
10. The patient has a functioning CSF shunt device
11. The patient has shown an intolerance to an implanted device


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Treatment of Metachromatic Leukodystrophy
MedDRA version: 19.1 Level: PT Classification code 10067609 Term: Metachromatic leukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: SHP611
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
Current Sponsor code: SHP611
Other descriptive name: Recombinant Human Arylsulfatase A (rhASA)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

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, and 364)

Secondary Objective: - To evaluate the effects of IT administration of HGT-1110 on gross motor function
- To evaluate the effects of IT administration of HGT-1110 on the ability to swallow
- To evaluate the effects of IT administration of HGT-1110 on nerve conduction velocity
- To evaluate the effect of IT administration of HGT-1110 on adaptive behavior
- 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 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)
- Determination of the presence of anti-HGT-1110 antibodies in CSF and/or serum

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 Outcome(s)

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, and 364. These efficacy outcome assessments are the GMFM-88, GIMF-C, GIMF-S, FEES, ENG studies, the VABS-II, the COMFORT questionnaire, sample collection for biomarker assessments (serum, CSF, and urine), and brain magnetic resonance imaging (MRI)/ magnetic resonance spectroscopy (MRS).

Secondary end point(s): The secondary endpoints of this study are:
- Change from baseline at Week 104 in motor function using the Gross Motor Function Measure-88 (GMFM-88) total score
- Change from baseline at Week 104 in the ability to swallow as measured by the Functional Endoscopic Evaluation of Swallowing (FEES)
- Change from baseline at Week 104 in nerve conduction as measured by the electroneurography (ENG) assessments of nerve conduction velocity (NCV), compound motor action potential (CMAP), amplitude (AMP), and distal latency (DL)
- Change from baseline at Week 104 in the adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS II)
- Change from baseline at Week 104 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

Secondary ID(s)

HGT-MLD-071

2012-003775-20-DE

Source(s) of Monetary Support

Shire HGT, Inc

Ethics review

Status: Approved
Approval date: 01/03/2017
Contact: