E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056886 |
E.1.2 | Term | Mucopolysaccharidosis I |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the antibody response to Aldurazyme in newly treated severe MPS I patients following an antigen-specific immunosuppressive regimen. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of Aldurazyme and the immunosuppressive regimen in severe MPS I patients
- To evaluate the reduction in urinary glycosaminoglycan (uGAG) excretion in severe MPS I patients treated with Aldurazyme following the antigen-specificimmunosuppressive regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patient’s parent(s) or legal guardian(s) willing and able to provide written informed consent, after the nature of the trial has been explained.
• Patient’s parent(s) or legal guardian(s) allow their child’s participation and are willing and able to comply with the trial procedures.
• Less than 5 years of age at the time of enrollment.
• Clinical diagnosis of severe MPS I (Hurler syndrome).
• Confirmed presence of 2 nonsense mutations in the IDUA gene (eg, compound heterozygosity or homozygosity).
• Confirmed α-L-iduronidase deficiency with a fibroblast, plasma, serum, or leukocyte α-L-iduronidase enzyme activity level |
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E.4 | Principal exclusion criteria |
•Clinically significant organic disease including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in
the trial or potentially decrease survival.
• Prior treatment with Aldurazyme.
• Known severe hypersensitivity to any excipients of the delivery solution for Aldurazyme.
• Prior HSCT (regardless of outcome) or currently under consideration for such a transplant. If a family later decides to obtain a haematopoeitic stem cell transplant (HSCT), the patient will be discontinued from the trial.
• Receipt of an investigational product within the 30 days prior to enrollment.
• Prior treatment in any experimental protocol (eg, fibroblast injections) that might potentially induce antibodies to laronidase or might affect the interpretation of an antibody response to laronidase.
• Receipt of vaccination(s) within 1 month prior to enrollment, or unwilling to postpone vaccinations during the period of participation in the trial.
• Homozygous thiopurine methyltransferase (TPMT) deficiency, as determined by genotype (the presence of two known null alleles for TPMT) or phenotype (near to complete absence of TPMT enzyme activity). |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Number of Participants Who Achieved Immune Tolerance Induction : 24 weeks after start of full-dose laronidase therapy
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 |
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E.5.2 | Secondary end point(s) |
•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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Percent Reduction of Urinary Glycosaminoglycan (uGAG) Level From Baseline to the End of Treatment/Early Withdrawal : Baseline, end of treatment/early withdrawal (up to 24 weeks after start of full-dose laronidase therapy)
•Urinary Glycosaminoglycan (uGAG) Levels: concentration of glycosaminoglycan (GAG) relative to creatinine in urine. A greater decrease in uGAG level indicates a greater response.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Brazil |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |