A phase III, single-arm, cross-over, multicenter clinical trial to compare efficacy and safety of P046 (laronidase; CinnaGen) versus laronidase (Aldurazyme®; Genzyme, BioMarin) in patients with Mucopolysaccharidosis type I (MPS I)
The Primary objective of this clinical trial is to assess efficacy of P046 (Laronidase produced by CinnaGen Co.) in comparison with Aldurazyme® (Laronidase produced by Genzyme, BioMarin) in patients with mucopolysaccharidosis type I (MPS I).
Design
Phase III, single arm, open-label, cross-over, and multicenter clinical trial
Settings and conduct
.Phase III, open labeled, one armed, cross over, active controlled, with 1:1 allocation and sample size 12, in Tehran - Iran.
Participants/Inclusion and exclusion criteria
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.
Intervention groups
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 P046 (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.
Main outcome variables
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
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N30
Registration date:2022-05-02, 1401/02/12
Registration timing:prospective
Last update:2022-05-02, 1401/02/12
Update count:2
Registration date
2022-05-02, 1401/02/12
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-05-22, 1401/03/01
Expected recruitment end date
2023-05-22, 1402/03/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A phase III, single-arm, cross-over, multicenter clinical trial to compare efficacy and safety of P046 (laronidase; CinnaGen) versus laronidase (Aldurazyme®; Genzyme, BioMarin) in patients with Mucopolysaccharidosis type I (MPS I)
Public title
A phase III clinical trial to assess efficacy and safety of P046 (laronidase; CinnaGen)
Purpose
Treatment
Inclusion/Exclusion criteria
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)
Age
From 5 years old to 18 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
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.
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Crossover
Other design features
This clinical trial consists of screening visit, visits 1 to 24, and final visit. After screening, the interval between visits is one week.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Tehran University of Medical Sciences
Street address
Sixth floor, Research Deputy of Tehran University of Medical Sciences, Ghods Street, Keshavarz Boulvard
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2022-03-17, 1400/12/26
Ethics committee reference number
IR.TUMS.TIPS.REC.1401.001
Health conditions studied
1
Description of health condition studied
Patients with Mucopolysaccharidosis type I (MPS I)
ICD-10 code
E76.0
ICD-10 code description
Mucopolysaccharidosis, type I
Primary outcomes
1
Description
Mean level of urinary Glycosaminoglycan adjusted by the level of urinary creatinine
Timepoint
Visits 9, 11, and 13 (related to the treatment with Aldurazyme®) and visits 21, 23, and final visit (related to the treatment with P046)
Method of measurement
Liquid chromatography tandem mass spectrometry
Secondary outcomes
1
Description
Distance traveled (based on meters) in 6 minutes (6-minute walk test)
Timepoint
Visits 1, 13, and Final
Method of measurement
Timer and meter
2
Description
Forced Vital Capacity percentage
Timepoint
Visits 1, 13, and Final
Method of measurement
Spirometer
3
Description
Adverse events
Timepoint
At all visits
Method of measurement
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.
Immediately after, half an hour after, and 1.5 hours after the infusion of medicine at visits 12 and 24
Method of measurement
Liquid chromatography tandem mass spectrometry or High-throughput mass spectrometry
Intervention groups
1
Description
Intervention group: Patients will receive Aldurazyme® (laronidase produced by Genzyme, BioMarin) from visits 1 to 12 (weekly) and will receive P046 (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.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Pediatric Medical Center, Building No. 2, Metabolic Laboratory of Pediatric Medical Center
Full name of responsible person
Dr. Ali Rabani
Street address
End of Keshavarz Boulevard, Dr. Gharib St., No. 62, Pediatric Medical Center, Building No. 2, Metabolic Laboratory of Pediatric Medical Center
City
Tehran
Province
Tehran
Postal code
14197333141
Phone
+98 21 6657 5730
Fax
+98 21 6694 9662
Email
gdrc@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
CinnaGen company
Full name of responsible person
Dr. Haleh Hamedifar
Street address
CinnaGen research and production Company, Simin Dasht Industrial Park, Karaj, Alborz, Iran
City
Karaj
Province
Alborz
Postal code
3165933155
Phone
+98 26 3667 0980
Email
cinnagen@cinnagen.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?