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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01887938




Registration number
NCT01887938
Ethics application status
Date submitted
20/06/2013
Date registered
27/06/2013

Titles & IDs
Public title
An Efficacy and Safety Study of HGT-1110 in Participants With Metachromatic Leukodystrophy
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
Secondary ID [1] 0 0
2012-003775-20
Secondary ID [2] 0 0
HGT-MLD-071
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metachromatic Leukodystrophy (MLD) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - HGT-1110

Experimental: Cohort 1 - Participants will receive 10 milligram (mg) of HGT-1110 (Recombinant human arylsulfatase A) intrathecal (IT) injection every-other-week (EOW).

Experimental: Cohort 2 - Participants will receive 30 mg of HGT-1110 IT injection EOW.

Experimental: Cohort 3 - Participants will receive 100 mg of HGT-1110 IT injection EOW.

Experimental: Cohort 4 - Participants will receive 100 mg of HGT-1110 IT injection once weekly for 12 weeks followed by 150 mg EOW.


Treatment: Other: HGT-1110
Participants will receive IT injection of HGT-1110.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Baseline to Follow-up (Week 628)
Primary outcome [2] 0 0
Presence of Anti-HGT-1110 Antibodies in Cerebrospinal Fluid (CSF) and Serum
Timepoint [2] 0 0
Baseline until end of the study (Week 624)
Secondary outcome [1] 0 0
Change From Baseline in Motor Function as Assessed by Gross Motor Function Measure (GMFM-88) Total Score at Week 624
Timepoint [1] 0 0
Baseline, Week 624
Secondary outcome [2] 0 0
Change From Baseline in the Adaptive Behavior Composite Standard Score Measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
Timepoint [2] 0 0
Baseline, Week 624
Secondary outcome [3] 0 0
Change From Baseline in the Domain-Specific Caregiver Observed Metachromatic Leukodystrophy Functioning and Outcomes Reporting Tool (COMFORT) Scores
Timepoint [3] 0 0
Baseline, Week 624
Secondary outcome [4] 0 0
Maximum Observed Serum Concentration (Cmax) of HGT-1110
Timepoint [4] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [5] 0 0
Time of Maximum Observed Serum Concentration (Tmax) of HGT-1110
Timepoint [5] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [6] 0 0
Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time at Which Serum Concentrations Were Measurable (AUC0-last) of HGT-1110
Timepoint [6] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [7] 0 0
Area Under the Serum Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of HGT-1110
Timepoint [7] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [8] 0 0
Apparent Terminal Rate Constant (lambda z) of HGT-1110
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [9] 0 0
Terminal Half-Life (t1/2) of HGT-1110
Timepoint [9] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [10] 0 0
Clearance (CL/F) of HGT-1110
Timepoint [10] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [11] 0 0
Volume of Distribution (Vz/F) of HGT-1110
Timepoint [11] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours post-dose on Weeks 104, 258, 364 and 622 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [12] 0 0
Concentrations of HGT-1110 in Cerebrospinal Fluid (CSF)
Timepoint [12] 0 0
Baseline to End of the study (Week 624)

Eligibility
Key inclusion criteria
1. Participant has participated in Study HGT-MLD-070 (NCT01510028) through Week 40.
2. Participant must have no safety or medical issues that contraindicate participation.
3. The participant, participant'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.
Minimum age
0 Years
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The participant is unable to comply with the protocol (example, 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 participant 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 participant is pregnant or breastfeeding.
5. The participant 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 (NCT01510028) within 6 months prior to study enrollment or at any time during the study.
6. The participant has a condition that is contraindicated as described in the SOPH-A-PORT Mini SIDDD Instructions for Use (IFU), including:

1. The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
2. The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the investigator.
3. The participant has a known or suspected local or general infection.
4. The participant is at risk of abnormal bleeding due to a medical condition or therapy.
5. The participant has one or more spinal abnormalities that could complicate safe implantation or fixation.
6. The participant has a functioning CSF shunt device.
7. The participant has shown an intolerance to an implanted device.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Porto Alegre
Country [2] 0 0
Czechia
State/province [2] 0 0
Brno
Country [3] 0 0
Denmark
State/province [3] 0 0
Copenhagen
Country [4] 0 0
France
State/province [4] 0 0
Ile-de-France
Country [5] 0 0
France
State/province [5] 0 0
Bron Cedex
Country [6] 0 0
France
State/province [6] 0 0
Montpellier
Country [7] 0 0
France
State/province [7] 0 0
Nantes Cedex 1
Country [8] 0 0
France
State/province [8] 0 0
Orleans
Country [9] 0 0
Germany
State/province [9] 0 0
Baden-Wuerttemberg
Country [10] 0 0
Germany
State/province [10] 0 0
Oldenburg
Country [11] 0 0
Germany
State/province [11] 0 0
Wesel
Country [12] 0 0
Japan
State/province [12] 0 0
Fukuoka
Country [13] 0 0
Japan
State/province [13] 0 0
Okayama Prefecture
Country [14] 0 0
Japan
State/province [14] 0 0
Osaka

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Shire
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Takeda Development Center Americas, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Shire
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
- De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, ...)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT01887938