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Mucopolysaccharidosis IPhase 1/2NCT00741338

Immune Tolerance Study With Aldurazyme® (Laronidase)

A Phase 1/2 study testing Laronidase, Cyclosporine A (CsA) and Azathioprine (Aza) in people with Mucopolysaccharidosis I, run by Genzyme, a Sanofi Company at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to see if treatment with an antigen-specific immunosuppressive can decrease or stop an antibody response to laronidase (Aldurazyme®) during enzyme replacement therapy with laronidase in severe Mucopolysaccharidosis I (MPS I) participants. Read more about this study

Who is it for?
Ages Up to 5 years
Conditions the study is for
Mucopolysaccharidosis I
What is being tested?
Laronidase, Cyclosporine A (CsA) and Azathioprine (Aza)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesin 2 countries
Study dates
Sep 2008to Sep 2012
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 Up to 5 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion)
  • Participant's parent(s) or legal guardian(s) allow their child's participation and are willing and able to comply with trial procedures
  • The participant must be up to and including 5 years of age at the time of enrollment
  • Clinical diagnosis of the severe (Hurler) phenotype of MPS I
  • Confirmed presence of 2 nonsense mutations in the alfa-L-iduronidase (IDUA) gene (that is, compound heterozygosity or homozygosity). For the purpose of enrollment, genotyping may be performed by a local laboratory. If no genotyping is performed by a local laboratory, a sample is collected for analysis by a central laboratory before enrollment
  • Documented IDUA deficiency with fibroblast, plasma, serum, leukocyte or dried blood spot IDUA enzyme activity assay

Who cannot join

  • The participant has a clinically significant organ disease including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness or extenuating circumstances that, in the opinion of the investigator, precludes participation in the trial or potentially decrease survival
  • The participant has previously received treatment with laronidase
  • The participant has known severe hypersensitivity to any excipients of the delivery solution for laronidase or to any of the other investigational drugs used in the study
  • The participant has undergone a haematopoietic stem cell transplant (HSCT), regardless of outcome, or is currently under consideration for such a transplant. If a family later decides to obtain HSCT, the participant will be discontinued from the trial
  • The participant has received an investigational product within the 30 days prior to enrollment
  • The participant has prior treatment in any experimental protocol (for example, fibroblast injections) that might potentially induce antibodies to laronidase or might affect the interpretation of the participant's antibody response to laronidase
Show all 9Show fewer
  • The participant has received vaccination(s) within 1 month prior to enrollment, or is unwilling to postpone vaccinations during the Tolerance Induction Period in the trial
  • The participant is homozygous for thiopurine methyltransferase (TPMT) deficiency, as determined by the genotype (the presence of 2 known null alleles for TPMT) or phenotype (near to complete absence of TPMT enzyme activity)
  • The participant has a prior history of tuberculosis or a positive test for latent tuberculosis infection

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Brazil1 site

  • HCPA

    Porto Alegre

Other trials in Brazil

Russia1 site

  • Moscow Research Institute for Pediatrics and Children Surgery

    Moscow

Other trials in Russia

About this study

Official title: A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase)

The purpose of this study is to see if treatment with an antigen-specific immunosuppressive can decrease or stop an antibody response to laronidase (Aldurazyme®) during enzyme replacement therapy with laronidase in severe Mucopolysaccharidosis I (MPS I) participants.

Being tested
Laronidase, Cyclosporine A (CsA), Azathioprine (Aza)
Keywords
MPS I, Mucopolysaccharidosis, Hurler syndrome
Medical subject headings
Mucopolysaccharidosis I, Mucopolysaccharidoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LaronidaseBiological

    Also called Aldurazyme®

    0.058 mg/kg - 0.58 mg/kg IV infusion weekly.

  • Cyclosporine A (CsA)Drug

    Also called Neoral®

    Orally three times daily.

  • Azathioprine (Aza)Drug

    Also called Imuran®

    Orally either every day for Cohort 1 or every other day for Cohort 2.

Study groups in NCT00741338
Study groupRoleWhat they receive
Cohort 1ExperimentalTolerance Induction Period (TIP): Cyclosporine A (CsA) starting at 5 milligram per kilogram (mg/kg) orally three times daily until the target trough concentration of at least 350 nanogram per milliliter (ng/mL) (preferably 400 ng/mL) achieved along with azathioprine (Aza) 2.5 mg/kg/day orally. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly intravenous (IV) infusion (starting from Day 1) up to Week 12. CsA and Aza were gradually discontinued. Immune Challenge Period (ICP): following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 39.
Receives: Biological: Laronidase; Drug: Cyclosporine A (CsA); Drug: Azathioprine (Aza)
Cohort 2ExperimentalTIP: CsA starting at 6.7 mg/kg orally three times daily until the target trough concentration of at least 350 ng/mL (preferably 400 ng/mL) achieved along with Aza 5 mg/kg orally every other day. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly IV infusion (starting from Day 1) up to Week 18. CsA and Aza were gradually discontinued. ICP: following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 45.
Receives: Biological: Laronidase; Drug: Cyclosporine A (CsA); Drug: Azathioprine (Aza)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Achieved Immune Tolerance Induction

    Immune tolerance induction success was defined as development of an anti-laronidase immunoglobulin G (IgG) antibody titer less than or equal to (<=) 1:3200 after 24 weeks of receiving full-dose (0.58 mg/kg) laronidase therapy.

    Measured: 24 weeks after start of full-dose laronidase therapy

Secondary outcomes (1)

  1. Percent Reduction of Urinary Glycosaminoglycan (uGAG) Level From Baseline to the End of Treatment/Early Withdrawal

    Urinary Glycosaminoglycan (uGAG) Levels: concentration of glycosaminoglycan (GAG) relative to creatinine in urine. A greater decrease in uGAG level indicates a greater response.

    Measured: Baseline, end of treatment/early withdrawal (up to 24 weeks after start of full-dose laronidase therapy)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionSep 2012
  4. Study completionSep 2012

Resources

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00741338
Sponsor's protocol ID
ALID02307
Other IDs
2007-001163-30
Status last verified
Jun 2014
First submitted
13 Aug 2008
Last updated
2 Jul 2014
Data monitoring committee
Yes

Publications

  • Giugliani R, Vieira TA, Carvalho CG, Munoz-Rojas MV, Semyachkina AN, Voinova VY, Richards S, Cox GF, Xue Y. Immune tolerance induction for laronidase treatment in mucopolysaccharidosis I. Mol Genet Metab Rep. 2017 Jan 13;10:61-66. doi: 10.1016/j.ymgmr.2017.01.004. eCollection 2017 Mar.

    PubMed 28119821

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Laronidase, Cyclosporine A (CsA) and Azathioprine (Aza) in people with Mucopolysaccharidosis I, run by Genzyme, a Sanofi Company at 2 sites in 2 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 6 inclusion and 9 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 2 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Brazil, Russia. 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 2 Jul 2014). 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?

Number of Participants Who Achieved Immune Tolerance Induction (time frame: 24 weeks after start of full-dose laronidase therapy). 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 NCT00741338, 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 2 Jul 2014.

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