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)
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Recruitment centers
#1
Name of recruitment center - English: Pediatric Medical Center, Building No. 2, Metabolic Laboratory of Pediatric Medical Center
Name of recruitment center - Persian: مرکز تحقیقات رشد و تکامل، آزمایشگاه متابولیک ایران
Full name of responsible person - English: Dr. Ali Rabani
Full name of responsible person - Persian: دکتر علی ربانی
Street address - English: End of Keshavarz Boulevard, Dr. Gharib St., No. 62, Pediatric Medical Center, Building No. 2, Metabolic Laboratory of Pediatric Medical Center
Street address - Persian: انتهای بلوار کشاورز،خیابان دکتر قریب، پلاک 62، مرکز طبی کودکان، ساختمان شماره 2، آزمایشگاه متابولیک مرکز طبی کودکان
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 14197333141
Phone: +98 21 6657 5730
Fax: +98 21 6694 9662
Email: gdrc@tums.ac.ir
Web page address:
Name of recruitment center - English: Growth and Development Research Center, Iran Metabolic Laboratory
Name of recruitment center - Persian: مرکز تحقیقات رشد و تکامل، آزمایشگاه متابولیک ایران
Full name of responsible person - English: Dr. Ali Rabani - Dr. Aria Setoodeh
Full name of responsible person - Persian: دکتر علی ربانی - دکتر آریا ستوده
Street address - English: Metabolic Laboratory of Pediatric Medical Center, Building No. 2,No. 62, Pediatric Medical Center, Dr. Gharib St, End of Keshavarz Boulevard
Street address - Persian: انتهای بلوار کشاورز،خیابان دکتر قریب، پلاک 62، مرکز طبی کودکان، ساختمان شماره 2، آزمایشگاه متابولیک مرکز طبی کودکان
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 14197333141
Phone: +98 21 6657 5730
Fax: +98 21 6694 9662
Email: gdrc@tums.ac.ir
Web page address:
Name of recruitment center - English: Pediatric MedicalGrowth and Development Research Center, Building No. 2,Iran Metabolic Laboratory of Pediatric Medical Center Name of recruitment center - Persian: مرکز تحقیقات رشد و تکامل، آزمایشگاه متابولیک ایران Full name of responsible person - English: Dr. Ali Rabani - Dr. Aria Setoodeh Full name of responsible person - Persian: دکتر علی ربانی - دکتر آریا ستوده Street address - English: EndMetabolic Laboratory of Keshavarz Boulevard, Dr. Gharib St., No. 62, Pediatric Medical Center, Building No. 22,No. 62, Metabolic Laboratory of Pediatric Medical Center, Dr. Gharib St, End of Keshavarz Boulevard Street address - Persian: انتهای بلوار کشاورز،خیابان دکتر قریب، پلاک 62، مرکز طبی کودکان، ساختمان شماره 2، آزمایشگاه متابولیک مرکز طبی کودکان City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 14197333141 Phone: +98 21 6657 5730 Fax: +98 21 6694 9662 Email: gdrc@tums.ac.ir Web page address:
#2
Name of recruitment center - English: Loqmane Hakim Hospital
Name of recruitment center - Persian: بیمارستان لقمان حکیم
Full name of responsible person - English: Dr. Shadab Salehpour
Full name of responsible person - Persian: دکتر شاداب صالح پور
Street address - English: Tehran, South Kargar St., Kamali St., Loqmane Hakim Hospital
Street address - Persian: تهران، خیابان کارگر جنوبی، خیابان کمالی، بیمارستان لقمان حکیم
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 1333635445
Phone: +98 21 5541 9005
Fax: +98 21 5541 9009
Email: loghman.hospital@sbmu.ac.ir
Web page address:
Name of recruitment center - English: Loqmane Hakim Hospital Name of recruitment center - Persian: بیمارستان لقمان حکیم Full name of responsible person - English: Dr. Shadab Salehpour Full name of responsible person - Persian: دکتر شاداب صالح پور Street address - English: Tehran, South Kargar St., Kamali St., Loqmane Hakim Hospital Street address - Persian: تهران، خیابان کارگر جنوبی، خیابان کمالی، بیمارستان لقمان حکیم City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 1333635445 Phone: +98 21 5541 9005 Fax: +98 21 5541 9009 Email: loghman.hospital@sbmu.ac.ir Web page address:
#3
Name of recruitment center - English: Mofid Children's Hospital
Name of recruitment center - Persian: بیمارستان کودکان مفید
Full name of responsible person - English: Dr. Mohammad Reza Alaei - Dr. Marjan Shakiba
Full name of responsible person - Persian: دکتر محمدرضا علایی - دکتر مرجان شکیبا
Street address - English: Tehran, Shariati St., above Hosseinieh Irshad, Mofid Children's Hospital
Street address - Persian: تهران، خیابان شریعتی، بالاتر از حسینیه ارشاد، بیمارستان کودکان مفید
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 15514 – 15468
Phone: +98 21 2222 7021
Fax:
Email: info-mch@sbmu.ac.ir
Web page address:
Name of recruitment center - English: Mofid Children's Hospital Name of recruitment center - Persian: بیمارستان کودکان مفید Full name of responsible person - English: Dr. Mohammad Reza Alaei - Dr. Marjan Shakiba Full name of responsible person - Persian: دکتر محمدرضا علایی - دکتر مرجان شکیبا Street address - English: Tehran, Shariati St., above Hosseinieh Irshad, Mofid Children's Hospital Street address - Persian: تهران، خیابان شریعتی، بالاتر از حسینیه ارشاد، بیمارستان کودکان مفید City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 15514 – 15468 Phone: +98 21 2222 7021 Fax: Email: info-mch@sbmu.ac.ir Web page address:
#4
Name of recruitment center - English: Akbar Children's Hospital
Name of recruitment center - Persian: بیمارستان کودکان اکبر
Full name of responsible person - English: Dr. Samaneh Nowrozi Asl - Dr. Peyman Eshraghi
Full name of responsible person - Persian: دکتر سمانه نوروزی اصل - دکتر پیمان اشراقی
Street address - English: Mashhad, Shahid Kaveh Boulevard, in front of Shahid Kaveh 14, Akbar Children's Hospital
Street address - Persian: مشهد، بلوار شهید کاوه، مقابل شهید کاوه ١۴، بیمارستان کودکان اکبر
City - English: Tehran
City - Persian: تهران
Province: Tehran
Country: Iran (Islamic Republic of)
Postal code: 9177897157
Phone: +98 51 3871 3801
Fax:
Email: ak.pr@mums.ac.ir
Web page address:
Name of recruitment center - English: Akbar Children's Hospital Name of recruitment center - Persian: بیمارستان کودکان اکبر Full name of responsible person - English: Dr. Samaneh Nowrozi Asl - Dr. Peyman Eshraghi Full name of responsible person - Persian: دکتر سمانه نوروزی اصل - دکتر پیمان اشراقی Street address - English: Mashhad, Shahid Kaveh Boulevard, in front of Shahid Kaveh 14, Akbar Children's Hospital Street address - Persian: مشهد، بلوار شهید کاوه، مقابل شهید کاوه ١۴، بیمارستان کودکان اکبر City - English: Tehran City - Persian: تهران Province: Tehran Country: Iran (Islamic Republic of) Postal code: 9177897157 Phone: +98 51 3871 3801 Fax: Email: ak.pr@mums.ac.ir Web page address:
Protocol summary
Study aim
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:2023-04-17, 1402/01/28
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
Ethics Committee of the Institute of Pharmaceutical Sciences (TIPS)
Street address
The Institute of Pharmaceutical Sciences (TIPS), Faculty of Pharmacy, Tehran University of Medical Sciences, Poursina Avenue
City
Tehran
Province
Tehran
Postal code
14176-13151
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
Growth and Development Research Center, Iran Metabolic Laboratory
Full name of responsible person
Dr. Ali Rabani - Dr. Aria Setoodeh
Street address
Metabolic Laboratory of Pediatric Medical Center, Building No. 2,No. 62, Pediatric Medical Center, Dr. Gharib St, End of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
14197333141
Phone
+98 21 6657 5730
Fax
+98 21 6694 9662
Email
gdrc@tums.ac.ir
2
Recruitment center
Name of recruitment center
Loqmane Hakim Hospital
Full name of responsible person
Dr. Shadab Salehpour
Street address
Tehran, South Kargar St., Kamali St., Loqmane Hakim Hospital