Protocol summary
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Study aim
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The Primary objective of this clinical trial is to assess efficacy of YW17 (Laronidase produced by CinnaGen Co.) in comparison with Aldurazyme® (Laronidase produced by Genzyme, BioMarin) in patients with mucopolysaccharidosis type I (MPS I).
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Design
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Phase III, single arm, open-label, cross-over, and multicenter clinical trial
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Settings and conduct
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.Phase III, open labeled, one armed, cross over, active controlled, with 1:1 allocation and sample size 12, in Tehran - Iran.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: Mucopolysaccharidosis type I patients, aged between 5 to 18 years; exclusion criteria: Prior bone marrow transplantation or being a candidate for receiving HSCT, prior Tracheotomy, pregnancy or lactation, circumstance that could significantly interfere with study compliance, severe organic disease not associated with mucopolysaccharidosis type I (MPS I), known hypersensitivity to laronidase or components of the laronidase solution, Abnormal renal function, acute hydrocephalus, patients who are naïve to laronidase.
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Intervention groups
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All patients will be in the intervention group. Patients will receive 0.58 milligram per kilogram of body weight of Aldurazyme® (laronidase produced by Genzyme, BioMarin) for 12 weeks and then will receive the same amount of YW17 (laronidase produced by Cinnagen Co.) for the next 12 weeks by intravenous infusion. In addition, to minimize possible infusion-related reactions, all patients will receive acetaminophen and diphenhydramine one hour before each injection.
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Main outcome variables
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Mean level of urinary Glycosaminoglycan adjusted by the level of urinary creatinine; Distance traveled (based on meters) in 6 minutes (6-minute walk test); Forced Vital Capacity percentage; Adverse events; Enzyme assay
General information
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Reason for update
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Manufacture code change
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20150303021315N30
Registration date:
2022-05-02, 1401/02/12
Registration timing:
prospective
Last update:
2024-08-11, 1403/05/21
Update count:
2
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Registration date
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2022-05-02, 1401/02/12
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2022-05-22, 1401/03/01
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Expected recruitment end date
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2023-05-22, 1402/03/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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A phase III, single-arm, cross-over, multicenter clinical trial to compare efficacy and safety of YW17 (laronidase; CinnaGen) versus laronidase (Aldurazyme®; Genzyme, BioMarin) in patients with Mucopolysaccharidosis type I (MPS I)
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Public title
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A phase III clinical trial to assess efficacy and safety of YW17 (laronidase; CinnaGen)
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Patients Aged Between 5 to 18 years
Mucopolysaccharidosis type I confirmed
Willingness and having informed consent (patient or his/her parents/ legal guardian) to participate in this study
Exclusion criteria:
Prior bone marrow transplantation
Being a candidate for receiving hematopoietic stem cell transplantation
Prior Tracheotomy
Pregnancy
Lactation
Administration of any investigational drug within 30 days before study enrollment
Medical condition or other circumstance that could significantly interfere with study compliance
The severe organic disease that is not associated with mucopolysaccharidosis type 1
Known hypersensitivity to laronidase or components of the laronidase solution
Abnormal renal function determined by measuring serum creatinine and blood urea nitrogen (BUN) levels
Acute hydrocephalus
Prescribing laronidase for the first time for the patient (naive patient)
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Age
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From 5 years old to 18 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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No information
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Sample size
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Target sample size:
12
More than 1 sample in each individual
Number of samples in each individual:
2
In this study, each person will take drug twice and compare with each other.
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Randomization (investigator's opinion)
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N/A
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Randomization description
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Crossover
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Other design features
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This clinical trial consists of screening visit, visits 1 to 24, and final visit. After screening, the interval between visits is one week.
Ethics committees
1
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Ethics committee
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Approval date
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2022-03-17, 1400/12/26
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Ethics committee reference number
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IR.TUMS.TIPS.REC.1401.001
Health conditions studied
1
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Description of health condition studied
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Patients with Mucopolysaccharidosis type I (MPS I)
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ICD-10 code
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E76.0
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ICD-10 code description
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Mucopolysaccharidosis, type I
Primary outcomes
1
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Description
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Mean level of urinary Glycosaminoglycan adjusted by the level of urinary creatinine
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Timepoint
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Visits 9, 11, and 13 (related to the treatment with Aldurazyme®) and visits 21, 23, and final visit (related to the treatment with YW17)
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Method of measurement
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Liquid chromatography tandem mass spectrometry
Secondary outcomes
1
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Description
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Distance traveled (based on meters) in 6 minutes (6-minute walk test)
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Timepoint
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Visits 1, 13, and Final
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Method of measurement
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Timer and meter
2
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Description
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Forced Vital Capacity percentage
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Timepoint
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Visits 1, 13, and Final
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Method of measurement
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Spirometer
3
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Description
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Adverse events
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Timepoint
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At all visits
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Method of measurement
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All adverse events are assessed through patient reporting, physician diagnosis, and are then classified by severity (based on common terminology criteria for adverse events (CTCAE)), seriousness and relationship to the study drug.
4
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Description
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Enzyme assay (α-L-iduronidase activity measurement)
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Timepoint
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Immediately after, half an hour after, and 1.5 hours after the infusion of medicine at visits 12 and 24
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Method of measurement
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Liquid chromatography tandem mass spectrometry or High-throughput mass spectrometry
Intervention groups
1
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Description
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Intervention group: Patients will receive Aldurazyme® (laronidase produced by Genzyme, BioMarin) from visits 1 to 12 (weekly) and will receive YW17 (laronidase produced by Cinnagen Co.) from visit 13 to 24. The Dosing of laronidase is 0.58 milligram per kilogram of patient’s body weight. Laronidase is administered by intravenous infusion in 3 to 4 hours. The dosage form of laronidase (Both products) is vial consisting of a solution with a concentration of 2.9 milligrams per 5 milliliters to be diluted in normal saline. To minimize possible infusion-related reactions, all patients will receive acetaminophen and diphenhydramine one hour before each injection.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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CinnaGen company
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available