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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01510028




Registration number
NCT01510028
Ethics application status
Date submitted
14/12/2011
Date registered
13/01/2012

Titles & IDs
Public title
Multicenter Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy (MLD)
Scientific title
A Phase I/II Multicenter Open-label Dose Escalation Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy
Secondary ID [1] 0 0
2011-002044-28
Secondary ID [2] 0 0
HGT-MLD-070
Universal Trial Number (UTN)
Trial acronym
IDEAMLD
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 - Recombinant human arylsulfatase A

Experimental: Cohort 1 (10 mg) - 6 patients treated with HGT-1110 10 mg EOW by IT injection

Experimental: Cohort 2 (30 mg) - 6 patients treated with HGT-1110 30 mg EOW by IT injection

Experimental: Cohort 3 (100 mg) - 6 patients treated with HGT-1110 100 mg EOW by IT injection

Experimental: Cohort 4 (100 mg) - 6 patients treated with HGT-1110 100 mg EOW by IT injection


Treatment: Other: Recombinant human arylsulfatase A
6 patients treated with HGT-1110 EOW by IT injection

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) by Type and Severity
Timepoint [1] 0 0
From start of study treatment up to Week 42
Primary outcome [2] 0 0
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
From start of study treatment up to Week 40
Primary outcome [3] 0 0
Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [3] 0 0
From start of study treatment up to Week 40
Primary outcome [4] 0 0
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
From start of study treatment up to Week 40
Primary outcome [5] 0 0
Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE)
Timepoint [5] 0 0
From start of study treatment up to Week 40
Primary outcome [6] 0 0
Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Timepoint [6] 0 0
From start of study treatment up to Week 40
Primary outcome [7] 0 0
Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum
Timepoint [7] 0 0
Baseline up to Week 40
Secondary outcome [1] 0 0
Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40
Timepoint [1] 0 0
Baseline, Week 40
Secondary outcome [2] 0 0
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40
Timepoint [2] 0 0
Week 40
Secondary outcome [3] 0 0
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40
Timepoint [3] 0 0
Week 40
Secondary outcome [4] 0 0
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40
Timepoint [4] 0 0
Week 40
Secondary outcome [5] 0 0
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40
Timepoint [5] 0 0
Week 40
Secondary outcome [6] 0 0
Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40
Timepoint [6] 0 0
Week 40
Secondary outcome [7] 0 0
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40
Timepoint [7] 0 0
Baseline, Week 40
Secondary outcome [8] 0 0
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40
Timepoint [8] 0 0
Baseline, Week 40
Secondary outcome [9] 0 0
Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40
Timepoint [9] 0 0
Baseline, Week 40
Secondary outcome [10] 0 0
Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40
Timepoint [10] 0 0
Baseline, Week 40
Secondary outcome [11] 0 0
Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40
Timepoint [11] 0 0
Baseline, Week 40
Secondary outcome [12] 0 0
Maximum Observed Serum Concentration (Cmax) of SHP611
Timepoint [12] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [13] 0 0
Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma
Timepoint [13] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [14] 0 0
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611
Timepoint [14] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [15] 0 0
Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611
Timepoint [15] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [16] 0 0
Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611
Timepoint [16] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [17] 0 0
First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611
Timepoint [17] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [18] 0 0
Terminal Elimination Half Life (t1/2) of SHP611
Timepoint [18] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [19] 0 0
Total Body Clearance (CL/F) After Intrathecal Administration of SHP611
Timepoint [19] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [20] 0 0
Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611
Timepoint [20] 0 0
Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Secondary outcome [21] 0 0
Concentration of SHP611 in Cerebrospinal Fluid
Timepoint [21] 0 0
Baseline, 4, 8, 12, 16, 20, 24, 28, 32, 36, and 40 weeks

Eligibility
Key inclusion criteria
Inclusion

For Cohorts 1-4:

1. Confirmed diagnosis of metachromatic leukodystrophy by both:

* Arylsulfatase A (ASA) deficiency by assay in leukocytes AND
* Elevated sulfatide in urine
2. Appearance of the first symptoms of disease at or before 30 months of age.

For Cohorts 1-3 only:
3. Ambulatory at the time of screening. The minimum level of function required to meet this criterion is defined as the ability to walk forward 10 steps with one hand held.
4. The patient is less than 12 years of age at the time of screening.

For Cohort 4 only:

3.1 Minimum motor function requirements:
1. A total GMFM-88 (percent) score =40 at the screening examination and a total GMFM-88 (percent) score =35 at the baseline examination, AND
2. GMFM-88 Dimension E: Walking, Running & Jumping, item 68 ("walk forward 10 steps with one hand held") score of at least 1 "initiates" at the screening and baseline examinations (if applicable).

4.1 The patient is less than 8 years of age at the time of screening.

For Cohorts 1-4:
5. Neurological signs of MLD must be present at the screening examination.
6. The patient and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
7. Patient's parent(s) or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the patient.
Minimum age
No limit
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from the study if there is evidence or history of any of the following criteria at screening:

For Cohorts 1-4:

1. History of hematopoietic stem cell transplantation (HSCT).
2. The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
3. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial.
4. The patient is enrolled in another clinical study that involves the use of any investigational product (drug or device) other than HGT-1110 or the IDDD used in this study within 30 days prior to study enrollment or at any time during the study.
5. The patient is pregnant or breastfeeding.
6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT

Mini S IDDD Instructions for Use (IFU), including:

1. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
2. 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.
3. The patient has a known or suspected local or general infection.
4. The patient is at risk of abnormal bleeding due to a medical condition or therapy.
5. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation.
6. The patient has a functioning CSF shunt device.
7. The patient 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
Completed
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
Denmark
State/province [1] 0 0
København
Country [2] 0 0
France
State/province [2] 0 0
Ile-de-France
Country [3] 0 0
Germany
State/province [3] 0 0
Baden-Wuerttemberg
Country [4] 0 0
Japan
State/province [4] 0 0
Suita

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Shire
Address
Country

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
Takeda
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?

Results publications and other study-related documents

No documents have been uploaded by study researchers.