Late Infantile Metachromatic LeukodystrophyPhase 1/2NCT00633139
Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
A Phase 1/2 study testing Recombinant human Arylsulfatase A (rhASA) in people with Late Infantile Metachromatic Leukodystrophy, run by Shire at 1 site in Denmark.
Trial summary
This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). Read more about this study
- Who is it for?
- Ages 1 year to 5 years
- Conditions the study is for
- Late Infantile Metachromatic Leukodystrophy
- What is being tested?
- Recombinant human Arylsulfatase A (rhASA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Jan 2007to 25 Nov 2008
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The patients from the Phase I trial must meet the following criteria to be enrolled in the study.
- Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
- The subject and his/her guardian(s) must have the ability to comply with the clinical protocol
Who cannot join
- Spasticity so severe to inhibit transportation
- Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that, in the opinion of the Investigator, would preclude participation in the trial
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
- Use of any investigational product other than rhASA within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Center, Open-Label, Non-Randomized, Uncontrolled, Multiple-Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Efficacy and Long Term Safety of HGT-1111 (Recombinant Human Arylsulfatase A [rhASA, Metazym]) for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). All patients will be offered continuing treatment in this study and will in this protocol receive 13 infusions, whereby the patients total have had 27 infusions of Metazym. One infusion will be given every other week. After a total of 52 weeks of treatment the subjects will continue treatment in a compassionate use protocol. Safety (AE/SAE) will be monitored at every visit.
- Being tested
- Recombinant human Arylsulfatase A (rhASA)
- Keywords
- Metazym, Late infantile, Metachromatic leukodystrophy, Long-term safety
- Medical subject headings
- Leukodystrophy, Metachromatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human Arylsulfatase A (rhASA)Biological
Also called Metazym, HGT-1111
intravenous infusion, every other week for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA) Receives: Biological: Recombinant human Arylsulfatase A (rhASA) |
| Cohort 2 | Experimental | Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA) Receives: Biological: Recombinant human Arylsulfatase A (rhASA) |
| Cohort 3 | Experimental | Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA) Receives: Biological: Recombinant human Arylsulfatase A (rhASA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Changes (%) in Gross Motor Function Measurement (GMFM)
Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean.
Measured: Baseline, 52 Weeks
Relative Change in Mullen's Scales of Early Learning
Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean.
Measured: Baseline, 52 Weeks
Secondary outcomes (1)
Change in Cerebrospinal Fluid (CSF) Sulfatide
Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.
Measured: Baseline, 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2008 (estimated)
- Study start22 Jan 2007
- Primary completion25 Nov 2008
- Study completion25 Nov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Late Infantile Metachromatic LeukodystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00633139
- Sponsor's protocol ID
- HGT-MLD-048
- Other IDs
- 2007-006345-40
- Status last verified
- May 2021
- First submitted
- 29 Feb 2008
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
I Dali C, Groeschel S, Moldovan M, Farah MH, Krageloh-Mann I, Wasilewski M, Li J, Barton N, Krarup C. Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study. Ann Clin Transl Neurol. 2021 Jan;8(1):66-80. doi: 10.1002/acn3.51254. Epub 2020 Dec 17.
PubMed 33332761
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Open-Label, Non-Randomized, Uncontrolled, Multiple-Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Efficacy and Long Term Safety of HGT-1111 (Recombinant Human Arylsulfatase A [rhASA, Metazym]) for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
- ClinicalTrials.gov ID
- NCT00633139
- Acronym / sponsor ID
- HGT-MLD-048
- Keywords
- Metazym, Late infantile, Metachromatic leukodystrophy, Long-term safety
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 22 Jan 2007 (actual)
- Primary completion
- 25 Nov 2008 (actual)
- Study completion
- 25 Nov 2008 (actual)
- First posted
- 11 Mar 2008 (estimated)
- Results
- Posted 15 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). All patients will be offered continuing treatment in this study and will in this protocol receive 13 infusions, whereby the patients total have had 27 infusions of Metazym. One infusion will be given every other week. After a total of 52 weeks of treatment the subjects will continue treatment in a compassionate use protocol. Safety (AE/SAE) will be monitored at every visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Recombinant human Arylsulfatase A (rhASA)Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA) |
| Cohort 2 | Experimental | Biological: Recombinant human Arylsulfatase A (rhASA)Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA) |
| Cohort 3 | Experimental | Biological: Recombinant human Arylsulfatase A (rhASA)Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA) |
Who may qualify
- Ages
- 1 year to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- The patients from the Phase I trial must meet the following criteria to be enrolled in the study.
- Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
- The subject and his/her guardian(s) must have the ability to comply with the clinical protocol
Key exclusion criteria (4 listed)
- Spasticity so severe to inhibit transportation
- Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that, in the opinion of the Investigator, would preclude participation in the trial
- Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
- Use of any investigational product other than rhASA within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human Arylsulfatase A (rhASA)Also: Metazym, HGT-1111intravenous infusion, every other week for 26 weeks | Biological | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Relative Changes (%) in Gross Motor Function Measurement (GMFM)
Time frame: Baseline, 52 Weeks
Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean.
Relative Change in Mullen's Scales of Early Learning
Time frame: Baseline, 52 Weeks
Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean.
1 secondary outcome
Change in Cerebrospinal Fluid (CSF) Sulfatide
Time frame: Baseline, 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33332761I Dali C, Groeschel S, Moldovan M, Farah MH, Krageloh-Mann I, Wasilewski M, Li J, Barton N, Krarup C. Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study. Ann Clin Transl Neurol. 2021 Jan;8(1):66-80. doi: 10.1002/acn3.51254. Epub 2020 Dec 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Recombinant human Arylsulfatase A (rhASA) in people with Late Infantile Metachromatic Leukodystrophy, run by Shire at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Changes (%) in Gross Motor Function Measurement (GMFM) (time frame: Baseline, 52 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00633139, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.