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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT01887938
Ethics application status
Date submitted
20/06/2013
Date registered
27/06/2013
Date last updated
11/06/2019

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
Other interventions - 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.


Other interventions: HGT-1110
Participants will receive IT injection of HGT-1110.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational drug product-related. TEAEs are defined as all AEs occurring or worsening at or after the first dose of investigational drug product in HGT-MLD-071 or ongoing from HGT-MLD-070 at the time of enrollment into HGT-MLD-071.
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 - The presence of anti-HGT-1110 antibodies in CSF and serum will be assessed.
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 - The GMFM-88 item scores can be used to calculate a domain-specific percent score for each of the 5 GMFM-88 dimensions, which are the following: Lying and rolling; Sitting; Crawling and kneeling; Standing; Walking, running, and jumping. Each of the 88 items is rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores range from 0% (no mobility) to a score of 100%, that is (i.e,) the score that can be obtained by an average 5-year-old or older child with normal motor abilities. The domain-specific percent scores are averaged to obtain the total score (percent).
Timepoint [1] 0 0
Baseline, Week 624
Secondary outcome [2] 0 0
Percent Change From Baseline in N-Aacetylaspartate/Creatine (NAA/Cr) Ratio in Deep White Matter of the Brain as Measured by Proton Magnetic Resonance Spectroscopy (MRS) at Week 624 - Percent change from baseline in NAA/Cr ratio in deep white matter of the brain as measured by proton MRS will be reported.
Timepoint [2] 0 0
Baseline, Week 624
Secondary outcome [3] 0 0
Percent Change From Baseline in Choline/Creatine Ratio in Deep White Matter of the Brain as Measured by Proton Magnetic Resonance Spectroscopy (MRS) at Week 624 - Percent change from baseline in choline/creatine ratio in deep white matter of the brain as measured by proton MRS will be reported.
Timepoint [3] 0 0
Baseline, Week 624
Secondary outcome [4] 0 0
Percent Change From Baseline in Lactate/Creatine Ratio in Deep White Matter of the Brain as Measured by Proton Magnetic Resonance Spectroscopy (MRS) at Week 624 - Percent change from baseline in lactate/creatine ratio in deep white matter of the brain as measured by proton MRS will be reported.
Timepoint [4] 0 0
Baseline, Week 624
Secondary outcome [5] 0 0
Change From Baseline in Nerve Conduction Velocity (NCV) at Week 624 - Change from baseline in NCV will be assessed.
Timepoint [5] 0 0
Baseline, Week 624
Secondary outcome [6] 0 0
Change From Baseline in Amplitude (AMP) at Week 624 - Change from baseline in AMP will be assessed.
Timepoint [6] 0 0
Baseline, Week 624
Secondary outcome [7] 0 0
Change From Baseline in Distal Latency (DL) at Week 624 - Change from baseline in DL will be assessed.
Timepoint [7] 0 0
Baseline, Week 624
Secondary outcome [8] 0 0
Change From Baseline in the Adaptive Behavior Composite Standard Score Measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) - The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning.
Timepoint [8] 0 0
Baseline, Week 624
Secondary outcome [9] 0 0
Change From Baseline in the Domain-Specific Caregiver Observed Metachromatic Leukodystrophy Functioning and Outcomes Reporting Tool (COMFORT) Scores - The COMFORT is a questionnaire that will be used to assess health status and the impact of disease on the ability of participants with MLD to carry out activities of daily life. The questionnaire is organized by 8 domains (that is, Personal Care, Positioning, Transfer or Mobility, Eating, Pain and Discomfort During the Day, Sleep, Emotions, Communication, Play and Leisure Activities) and will be completed by the participant's parent(s) or legal representative(s). It will be conducted in available validated languages. The COMFORT scores range from 0 to 100, with higher scores indicating a decline in the functioning.
Timepoint [9] 0 0
Baseline, Week 624
Secondary outcome [10] 0 0
Maximum Observed Serum Concentration (Cmax) of HGT-1110 - The Cmax of HGT-1110 will be assessed.
Timepoint [10] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [11] 0 0
Time of Maximum Observed Serum Concentration (Tmax) of HGT-1110 - The Tmax of HGT-1110 will be assessed.
Timepoint [11] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [12] 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 - The AUC0-last of HGT-1110 will be assessed.
Timepoint [12] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [13] 0 0
Area Under the Serum Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of HGT-1110 - The AUC0-inf of HGT-1110 will be assessed.
Timepoint [13] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [14] 0 0
Apparent Terminal Rate Constant (lambda z) of HGT-1110 - The lambda z of HGT-1110 will be assessed.
Timepoint [14] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [15] 0 0
Terminal Half-Life (t1/2) of HGT-1110 - The t1/2 of HGT-1110 will be assessed.
Timepoint [15] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [16] 0 0
Clearance (CL/F) of HGT-1110 - The CL/F of HGT-1110 will be assessed.
Timepoint [16] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [17] 0 0
Volume of Distribution (Vz/F) of HGT-1110 - The Vz/F of HGT-1110 will be assessed.
Timepoint [17] 0 0
Predose, 0.5, 1, 2, 4, 8, 12, 24, and 48 hours postdose on Weeks 104 and 258 in Cohort 4 and Week 8 in Cohorts 1-3
Secondary outcome [18] 0 0
Concentrations of HGT-1110 in Cerebrospinal Fluid (CSF) - Concentrations of HGT-1110 in CSF will be assessed.
Timepoint [18] 0 0
Baseline to End of the study (Week 624)

Eligibility
Key inclusion criteria
1. Participant has participated in Study HGT-MLD-070 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
No limit
Maximum age
13 Years
Gender
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 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: a. The participant has
had, or may have, an allergic reaction to the materials of construction of the
SOPH-A-PORT Mini S device; b. 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; c. The
participant has a known or suspected local or general infection; d. The participant is
at risk of abnormal bleeding due to a medical condition or therapy; e. The participant
has one or more spinal abnormalities that could complicate safe implantation or
fixation; f. The participant has a functioning CSF shunt device; g. 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/Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to collect long-term safety data in participants with
metachromatic leukodystrophy (MLD) who are receiving HGT-1110 and have participated in Study
HGT-MLD-070 through Week 40.
Trial website
https://clinicaltrials.gov/show/NCT01887938
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

Summary results
Other publications