Mucopolysaccharidosis IPhase 3NCT00912925
Clinical Study of Aldurazyme in Patients With Mucopolysaccharidosis (MPS) I
A Phase 3 study testing rhIDU (recombinant human-Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurlers Syndrome, run by Genzyme, a Sanofi Company at 4 sites in 3 countries.
Trial summary
This study is being conducted to demonstrate the safety and clinical efficacy of Aldurazyme treatment in MPS I patients Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Mucopolysaccharidosis I, Hurlers Syndrome, Hurler-Scheie Syndrome
- What is being tested?
- rhIDU (recombinant human-Alpha-L-Iduronidase)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Dec 2000to Sep 2001
- Phase
- Phase 3
- 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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The patient had a documented diagnosis of MPS I confirmed by measurable clinical signs and symptoms of MPS I and a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
- Female patients of childbearing potential had a negative pregnancy test (urine-beta-human chorionic gonadotropin (hCG)) at baseline (all female patients of childbearing potential and sexually mature male patients were advised to use a medically accepted method of contraception throughout the study).
- The patient was capable of standing independently for 6 minutes and walking a minimum of 5 meters within 6 minutes.
- The patient was capable of performing a reproducible FVC maneuver.
- The patient had a baseline FVC value that was less than or equal to 80% of the patient's predicted normal FVC value based on polgar predicted values for standing height for children 5 through 7 years of age and the Hankinson predicted values for ages 8 and above.
Who cannot join
- The patient had undergone a tracheostomy.
- The patient had previously undergone a bone marrow transplantation.
- The patient was pregnant or lactating.
- The patient has received an investigational drug within 30 days prior to study enrollment.
- The patient had a medical condition, serious intercurrent illness, or other extenuating circumstance that could have significantly interfered with study compliance including all prescribing evaluations and follow-up activities.
- The patient had a known hypersensitivity to rhIDU or to components of the active or placebo test solutions.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Study site
Chapel Hill, North Carolina
Study site
New York, New York
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I
This study is being conducted to demonstrate the safety and clinical efficacy of Aldurazyme treatment in MPS I patients
- Being tested
- rhIDU (recombinant human-Alpha-L-Iduronidase), Placebo
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhIDU (recombinant human-Alpha-L-Iduronidase)Biological
Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 units/kg (approximately 0.58mg/kg) administered intravenously over approximately 4 hours once weekly for 26 weeks.
PlaceboBiological
Patients in the Placebo-control group were administered a solution of 100mM sodium phosphate , 150mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over a time period of approximately 4 hours once weekly for 26 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patients in the placebo-control group were administered a solution of 100 millimolar (mM) sodium phosphate, 150 mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over approximately 4 hours once weekly for 26 weeks. Receives: Biological: Placebo |
| Aldurazyme treatment | Active comparator | Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 Units/kg (approximately 0.58 mg/kg = labeled dose) administered intravenously over approximately 4 hours once weekly for 26 weeks. Receives: Biological: rhIDU (recombinant human-Alpha-L-Iduronidase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC)
Percent Predicted Forced Vital Capacity (FVC): the maximal exhaled breathe volume following a maximal inhaled breath. Overall Change from Baseline to Week 26 in percent predicted FVC = (observed value)/(predicted value) * 100%). A higher value indicates a greater response.
Measured: Baseline to Week 26
Overall Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
Six Minute Walk Test (6MWT): Distance walked (measured in meters) in 6 minutes. A longer distance indicates a greater response.
Measured: Baseline to Week 26
Secondary outcomes (5)
Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)
Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. Overall change from Baseline to Week 26 in AHI. A greater decrease in events indicates a greater response.
Measured: Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Liver Volume
Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
Measured: Baseline to Week 26
Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score
CHAQ/HAQ) = Patient questionnaire that measures the degree of disability on a scale of 0 (no disability) to 3 (maximal disability). A lower score indicates a greater response.
Measured: Baseline to week 26
Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)
Active Joint Range of Motion (ROM): Shoulder Flexion Ability to maximally raise one's arm overhead without assistance. Shoulder range of motion (mean of left and right arms) measured in degrees (0-180) by goniometry. Greater degree of flexion indicates greater response.
Measured: Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels
Urinary Glycosaminoglycan (GAG) Levels: Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.
Measured: Baseline to Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2009 (estimated)
- Study startDec 2000
- Primary completionSep 2001
- Study completionSep 2001
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 Mucopolysaccharidosis IStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioMarin/Genzyme LLC
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00912925
- Sponsor's protocol ID
- ALID-003-99
- Status last verified
- Mar 2015
- First submitted
- 2 Jun 2009
- Last updated
- 7 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
PubMed 33874971
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I
- ClinicalTrials.gov ID
- NCT00912925
- Acronym / sponsor ID
- ALID-003-99
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Collaborators
- BioMarin/Genzyme LLC
- Study start
- Dec 2000
- Primary completion
- Sep 2001 (actual)
- Study completion
- Sep 2001 (actual)
- First posted
- 3 Jun 2009 (estimated)
- Results
- Posted 19 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to demonstrate the safety and clinical efficacy of Aldurazyme treatment in MPS I patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboPatients in the placebo-control group were administered a solution of 100 millimolar (mM) sodium phosphate, 150 mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over approximately 4 hours once weekly for 26 weeks. |
| Aldurazyme treatment | Active comparator | Biological: rhIDU (recombinant human-Alpha-L-Iduronidase)Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 Units/kg (approximately 0.58 mg/kg = labeled dose) administered intravenously over approximately 4 hours once weekly for 26 weeks. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- The patient had a documented diagnosis of MPS I confirmed by measurable clinical signs and symptoms of MPS I and a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
- Female patients of childbearing potential had a negative pregnancy test (urine-beta-human chorionic gonadotropin (hCG)) at baseline (all female patients of childbearing potential and sexually mature male patients were advised to use a medically accepted method of contraception throughout the study).
- The patient was capable of standing independently for 6 minutes and walking a minimum of 5 meters within 6 minutes.
- The patient was capable of performing a reproducible FVC maneuver.
- The patient had a baseline FVC value that was less than or equal to 80% of the patient's predicted normal FVC value based on polgar predicted values for standing height for children 5 through 7 years of age and the Hankinson predicted values for ages 8 and above.
Key exclusion criteria (6 listed)
- The patient had undergone a tracheostomy.
- The patient had previously undergone a bone marrow transplantation.
- The patient was pregnant or lactating.
- The patient has received an investigational drug within 30 days prior to study enrollment.
- The patient had a medical condition, serious intercurrent illness, or other extenuating circumstance that could have significantly interfered with study compliance including all prescribing evaluations and follow-up activities.
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 |
|---|---|---|
| rhIDU (recombinant human-Alpha-L-Iduronidase)Patients in the active treatment group received Aldurazyme intravenously at a dose of 100 units/kg (approximately 0.58mg/kg) administered intravenously over approximately 4 hours once weekly for 26 weeks. | Biological | Aldurazyme treatment |
| PlaceboPatients in the Placebo-control group were administered a solution of 100mM sodium phosphate , 150mM sodium chloride, and 0.001% polysorbate-80, adjusted to a pH of 5.8 administered intravenously over a time period of approximately 4 hours once weekly for 26 weeks. | Biological | Placebo |
Primary outcome
Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC)
Time frame: Baseline to Week 26
Percent Predicted Forced Vital Capacity (FVC): the maximal exhaled breathe volume following a maximal inhaled breath. Overall Change from Baseline to Week 26 in percent predicted FVC = (observed value)/(predicted value) * 100%). A higher value indicates a greater response.
Overall Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
Time frame: Baseline to Week 26
Six Minute Walk Test (6MWT): Distance walked (measured in meters) in 6 minutes. A longer distance indicates a greater response.
5 secondary outcomes
Overall Change From Baseline to Week 26 in Apnea/Hypopnea Index (AHI)
Time frame: Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Liver Volume
Time frame: Baseline to Week 26
Overall Change From Baseline to Week 26 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score
Time frame: Baseline to week 26
Overall Change From Baseline to Week 26 in Active Joint Range of Motion (ROM)
Time frame: Baseline to Week 26
Overall Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Levels
Time frame: Baseline to Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33874971Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rhIDU (recombinant human-Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurlers Syndrome, run by Genzyme, a Sanofi Company at 4 sites in 3 countries.
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 5 inclusion and 6 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 7 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Canada, Germany. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 19 Aug 2009). 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?
Overall Change From Baseline to Week 26 in Percent Predicted Forced Vital Capacity (FVC) (time frame: Baseline to Week 26). 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 NCT00912925, 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 7 Apr 2015.