Evaluation of efficacy and safety of a abobotulinum toxin type A produced by Ronak Pharmaceutical Company in comparision to the commercial product Dysport® in treating moderate-to-severe glabellar lines; A phase III randomized, double-blind,clinical trial
Determining the safety and efficacy of Biosimilar abobotulinum toxin type A produced by Ronac company compared to Dysport in the treatment of frown lines
Design
This study is a phase 3 clinical trial study that is conducted on 164 participants who are randomly divided into two groups.
Settings and conduct
This study is a randomized and double-blind clinical trial study that will be conducted in Tehran Razi Hospital. In this study, samples from patients with moderate to severe frown lines based on glabellar line severity criteria are selected and randomly divided into two groups.
Participants/Inclusion and exclusion criteria
Entry requirements: 1. Having informed consent 2. Suffering from moderate to severe frown lines 3- Having the age of 18 to 60 years. Exclusion conditions: 1. Allergy to formulation components 2. injection of botulinum toxin in the last 6 months. 3. Consumption of aminoglycosides, penicillamine, quinine, etc. 4. History of cosmetic surgery 5.Using products that cause reconstruction or forehead active change in Last 6 months. 6.any surgery on the facial muscles and scars in the study area 7. Facial surgeries on the upper face during the study 8.Diseases affecting neuromuscular activity 9.History of facial nerve paralysis 10.Face asymmetry 11.Eyelid ptosis or eyebrow 12.Any infection or acute skin disease in the injected areas 11.Pregnancy 12.Breastfeeding 13. Allergy to fillers 14. Planned facial cosmetic surgery 15.Severe atrophy or muscle weakness 16.Participation in other CTS related to botulinum neurotoxin products and fillers17. history of eyebrow tattoo or any other procedure
Intervention groups
including two groups; intervention group get abobotulinum toxin type A made by Ronac and the control group get drug made by Dysport.
Main outcome variables
1. Glabellar lines severity scale based on GLSS
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200731048257N2
Registration date:2024-10-11, 1403/07/20
Registration timing:prospective
Last update:2024-10-11, 1403/07/20
Update count:0
Registration date
2024-10-11, 1403/07/20
Registrant information
Name
Mehran Pouraqajani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8856 8654
Email address
himehran95@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2024-10-31, 1403/08/10
Expected recruitment end date
2025-04-30, 1404/02/10
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of efficacy and safety of a abobotulinum toxin type A produced by Ronak Pharmaceutical Company in comparision to the commercial product Dysport® in treating moderate-to-severe glabellar lines; A phase III randomized, double-blind,clinical trial
Public title
safety and effectiveness of Biosimilar Abobotulinum toxin type A in the treatment of moderate to severe frown lines
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Having informed consent
Suffering from moderate to severe frown lines in the state of maximum frown area according to the GLSS criterion
18 to 60 years old
Exclusion criteria:
Allergy to botulinum toxin or any of the components of the formulation
History of previous treatment with botulinum toxin in the last 6 months
Use of aminoglycosides, penicillamine, quinine, chloroquine, hydroxychloroquine, calcium channel blockers, anticoagulants
history of any cosmetic surgery (such as filler injection, chemical peeling and laser) in the last year
History of using products that regenerate the skin or actively change the forehead area or around it in the last 6 months
History of any surgery on facial muscles and forehead scars and surrounding areas (including eyebrows)
Any upper facial surgery or cosmetic procedure that may be performed during the study period
Diseases that can affect neuromuscular activity (such as myasthenia gravis, amyotrophic lateral sclerosis or Eaton-Lambert)
History of facial nerve palsy
Significant asymmetry in the face,
Eyelid or eyebrow ptosis due to facial paralysis or a history of facial paralysis
Any active infection or acute skin disease in the injected areas
Pregnancy (according to urinary B-HCG test)
breastfeeding
History of any sensitivity to injectable fillers in the facial area
Planned facial cosmetic surgery during the study
Severe atrophy or excessive muscle weakness in the target injection areas
History of participating in other clinical studies related to botulinum neurotoxin products and fillers within the last 6 months
History of eyebrow tattoo or any other procedure in the eyebrow area during the last month
Age
From 18 years old to 60 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Investigator
Data analyser
Sample size
Target sample size:
164
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization will be done by a biostatistician, using the R comprehensive archive network version 3.2.3. The entry of the participants into the control and intervention groups will be done in a randomized and balanced way using blocks of four (randomization block). The control group includes the participants who receive Dysport medicine and the intervention group receives the medicine made by Ronak. The generated randomization code will be labeled on the medicine vials and will be presented along with the randomized list of volunteers at the study site.
Blinding (investigator's opinion)
Double blinded
Blinding description
Participants, investigators, medical staff, Data collector, data analysis officer, and all staff of the sponsoring company and clinical research collaborators will be blinded to the treatments, but the medical staff responsible for assigning the randomization code and drugs for injection will not be blinded.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committees of School of Medicine- Tehran University of Medical Sciences
Street address
خیابان پورسینا
City
Tehran
Province
Tehran
Postal code
1461884513
Approval date
2024-09-30, 1403/07/09
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1403.275
Health conditions studied
1
Description of health condition studied
Frowning line
ICD-10 code
ICD-10 code description
Primary outcomes
1
Description
Glabellar lines severity (decrease of two or more in the GLSS)
Timepoint
It is measured on days 14, 90 and 120 after the intervention
Method of measurement
Glabellar lines severity scale based on GLSS
Secondary outcomes
1
Description
The degree of effectiveness (reduction of two or more in the GLSS scale) based on the doctor's opinion of the severity of frown lines at rest in the 30th day after injection
Timepoint
in the 30th day after injection
Method of measurement
according to the GLSS
2
Description
The degree of effectiveness (reduction of two or more in the GLSS scale) based on the doctor's opinion of the severity of frown lines at rest and the maximum frown according to the GLSS on days 14, 90 and 120 after injection
Timepoint
days14, 90 and 120 after injection
Method of measurement
according to the GLSS
3
Description
The degree of effectiveness (reduction of two or more on the GLSS scale) based on the volunteer's opinion of the severity of frown lines in resting states and the maximum frown according to self-assessment (SSA)on days 90, 14, 30 and 120 after injection
Timepoint
days 90, 14, 30 and 120 after injection
Method of measurement
according to self-assessment
4
Description
Determining the effective start date based on the evaluation of the candidate
Timepoint
14th days after injection
Method of measurement
according to self-assessment
5
Description
Cumulative dose received in each study group
Timepoint
on days 30, 14, 90 and 120 after injection
Method of measurement
Total doses injected
Intervention groups
1
Description
Intervention group: In this group, the vial containing 500 units of abobotulinum toxin type A manufactured by Ronak Pharmaceutical Company is mixed with 2.5 ml of injectable sodium chloride 0.9% and mixed slowly. Based on the physician's evaluation, 40 to a maximum of 60 units of poison are injected deep intramuscularly in 3 places of the glabellar muscles (1 injection in the procerus, 2 injections deeply in the corrugators intramuscularly). Also, after two weeks, the volunteer will be examined by a doctor and if the volunteer did not take a cumulative dose of 60 units in the first injection and and -according to the clinical judgment of the physician- the amount of 5 to 10 units, the touch-up dose of the drug is injected deep intramuscularly. In the amount of 5 to 10 units, the touch-up dose of the drug is injected deep intramuscularly
Category
Treatment - Drugs
2
Description
Control group: In this group, the vial containing 500 units of Abobotulinumtoxin A (Ltd Biopharm Ipsen ) is mixed with 2.5 ml of injectable sodium chloride 0.9% and mixed slowly. Based on the physician's evaluation, 40 to a maximum of 60 units of poison are injected deep intramuscularly in 3 places of the glabellar muscles (1 injection in the procerus, 2 injections deeply in the corrugators intramuscularly). Also, after two weeks, the volunteer will be examined by a doctor and if the volunteer did not take a cumulative dose of 60 units in the first injection and and -according to the clinical judgment of the physician- the amount of 5 to 10 units, the touch-up dose of the drug is injected deep intramuscularly. In the amount of 5 to 10 units, the touch-up dose of the drug is injected deep intramuscularly
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Razi skin Hospital
Full name of responsible person
Dr. Amir Hooshang Ehsani
Street address
Vahdat-e Eslami st.
City
Tehran
Province
Tehran
Postal code
1199663911
Phone
+98 21 5563 0553
Email
razihospital@sina.tums.ac.ir
Web page address
https://razihos.tums.ac.ir/
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Ronak Pharmaceutical Co.
Full name of responsible person
Dr. Masood Davoodi
Street address
North Sheikh-e Bahaiea st
City
Tehran
Province
Tehran
Postal code
1993644514
Phone
+98 21 9107 9170
Fax
+98 21 8862 2404
Email
info@ronakpharm.com
Web page address
https://ronakpharm.com/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Ronak Pharmaceutical Co.
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry
Person responsible for general inquiries
Contact
Name of organization / entity
Bagheiat-allah University of Medical Sciences
Full name of responsible person
Mehran Pouraghajani
Position
Bachelor
Latest degree
Bachelor
Other areas of specialty/work
Nursery
Street address
Mollasadra st.
City
Tehran
Province
Tehran
Postal code
1435915371
Phone
+98 31 5472 3386
Email
himehran1995@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Amir Hooshang Ehsani
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Dermatology
Street address
poursina street
City
Tehran
Province
Tehran
Postal code
1435915371
Phone
+98 31 5472 3386
Email
ehsanih@sina.tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Bagheiat-allah University of Medical Sciences
Full name of responsible person
Mehran Pouraghajani
Position
Bachelor of Science in Surgical Technology
Latest degree
Bachelor
Other areas of specialty/work
Nursery
Street address
Mollasdra st.
City
Tehran
Province
Tehran
Postal code
1435916471
Phone
+98 21 8856 8654
Email
himehran1995@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
Deidentified IPD related to outcome will be shared.
When the data will become available and for how long
The access period will begin 6 months after publication of the paper
To whom data/document is available
The data will be available only for academic researchers.
Under which criteria data/document could be used
Only meta-analysis in collaboration with the current study research team will be permitted.
From where data/document is obtainable
Researchers can request data by emailing Dr. Amir Hooshang Ehsani ehsanih@sina.tums.ac.ir
What processes are involved for a request to access data/document
Requested data will be sent by email after consideration and approval by the relevant authorities.