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: 23 May 2022
• Main ID: EUCTR2012-003775-20-DE
• Date of registration: 14/12/2012
• 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: 11/09/2013
• Target sample size: 24
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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, Czechia, Denmark, France, Germany, Italy, Japan, United Kingdom

Contacts

• Name: David Whiteman
• Affiliation: Takeda Pharmaceutical Company Limited

• Name: David Whiteman
• Affiliation: Takeda Pharmaceutical Company Limited

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. Undergoes bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), 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 (IFU), 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


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

Health Condition(s) or Problem(s) studied

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

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

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, 364, 390, 416, 442, 468, 494, 520, 546, 572, 598 and 624)

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.

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

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
- 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)

Secondary Outcome(s)

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
- Change from baseline at end of study in the adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS II)
- 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).

Secondary ID(s)

HGT-MLD-071

Source(s) of Monetary Support

Shire HGT, Inc

Ethics review

Status: Approved
Approval date: 11/09/2013
Contact: