History
# Registration date Revision Id
2 2020-11-07, 1399/08/17 160086
1 2019-06-30, 1398/04/09 95240
Changes made to previous revision
This is the first revision

Protocol summary

Study aim
The aim of this study is to assess non-inferiority of Aflibercept (CinnaGen co.) to Eylea® (Regeneron, USA) in terms ‎of achieving maintaining vision in patients with neovascular age-related macular degeneration.‎
Design
This is a phase III, randomize, parallel, double-blind and active-control with the sample size of 168 patients.‎
Settings and conduct
This is a multicenter, phase 3 clinical trial
Participants/Inclusion and exclusion criteria
Patients aged 55-80 years with primary active CNV subfoveal lesion secondary to AMD (according to the physician's decision based on the results of ocular examination, or OCT) and the ETDRS-best-corrected visual acuity index with the score of 20/40 to 20/320 with include to the study. This study has 34 exclusion criteria which include any prior ocular or systemic anti-VEGF therapy during the past 3 months, presence of scar, fibrosis, or atrophy in the central part of the fovea in the study eye, active intraocular inflammation in either eye and histories such as the history or evidence of diabetic retinopathy, diabetic macular edema and the history of uveitis in either eye.
Intervention groups
Intervention group 1: Aflibercept (CinnaGen Co, Iran) 2 mg by intravitreal injection every 4 weeks for the first 3 injections, followed by 2 mg every 8 weeks until week 48 of study. Intervention group 2: Eylea (Regeneron, USA) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 injections, followed by 2 mg every 8 weeks (every two months) Until week 48 of study.
Main outcome variables
Assessing the main outcome is based on evaluating visual acuity with Tumbling-E ETDRS chart

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20150303021315N14
Registration date: 2019-06-30, 1398/04/09
Registration timing: prospective

Last update: 2019-06-30, 1398/04/09
Update count: 1
Registration date
2019-06-30, 1398/04/09
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
2019-07-23, 1398/05/01
Expected recruitment end date
2020-03-19, 1398/12/29
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A Phase III, multicenter, randomized, two-armed, double-blind, ‎parallel, active-controlled, non-inferiority clinical trial to compare efficacy ‎and safety of test-Aflibercept (CinnaGen Co, Iran) to the reference ‎Aflibercept product (Eylea®, Regeneron, USA) in patients with ‎Neovascular age-related macular degeneration.‎
Public title
The Effect of Aflibercept on Treatment of Age-related macular Degeneration
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
male or female aged 55-80 years at the time of signing the informed consent form.‎ Patients with Primary active CNV subfoveal lesion secondary to AMD (with definite diagnosis of AMD ‎according to physician’s decision based on the results of ocular examination, or OCT)‎ the ETDRS-best-corrected visual acuity index with the score of 20/40 to 20/320 (or BCVA letter score of ‎‎73 to 25 in the study eye)‎ Willing, committed, and able to return for clinic visits and complete all study-related procedures Patients with the ability to read, understand and willing to sign the informed consent form for participation ‎in the study
Exclusion criteria:
Any prior ocular (in the study eye) or systemic anti-VEGF therapy, during the past 3 months, Photodynamic ‎Therapy (PDT) or surgery for neovascular AMD.‎ The need for receiving ocular anti-VEGF simultaneously in both eyes in the loading phase for the treatment of ‎neovascular AMD Scar, fibrosis, or extensive subretinal hemorrhage of more than 50% of the total lesion area in the study eye, ‎according to the physician's opinion based on clinical presentation or according to fundus photography.‎ The presence of scar, fibrosis, or atrophy in the central part of the fovea in the study eye‎ The presence of retinal pigment epithelial tears or rips involving the macular part of the study eye at the time of ‎entering the study The history of any vitreous hemorrhage within 4 weeks prior to the first visit of the study in the study eye‎ Presence of other causes of CNV in the study eye‎ Clinical or paraclinical diagnosis of PCV by physician’s diagnosis‎ The history or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease ‎affecting the retina, other than AMD in either eyes‎ Prior vitrectomy in the study eye‎ History of retinal detachment or treatment or surgery for retinal detachment in the study eye‎ Any history of a macular hole of stage 2 or above in the study eye‎ Any intraocular or periocular surgery within three months of the screening visit on the study eye except lid surgery, ‎which may not have taken place within one month of screening visit‎ Prior trabeculectomy or any other filtration surgery in the study eye‎ Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma ‎medication) in the study eye‎ Active intraocular inflammation in either eye‎ Active ocular or periocular infection in either eye or any ocular or periocular infection within the last two weeks prior ‎to screening visit in either eye‎ Any history of uveitis in either eye‎ Presence or history of scleromalacia in either eye‎ Aphakia or pseudophakia with the absence of posterior capsule (unless it occurred as a result of a yttrium ‎aluminum garnet [YAG] posterior capsulotomy) in the study eye Previous therapeutic radiation in the region of the study eye‎ History of corneal transplant or corneal dystrophy in the study eye‎ Any significant media opacities, including cataract, in the study eye that might interfere with visual acuity, ‎assessment of drug safety, or fundus photography‎ Patients with amblyopia. Patients with blindness in the fellow eye Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could require either ‎medical or surgical intervention during the study period Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the ‎risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which ‎otherwise may interfere with the injection procedure or with evaluation of efficacy or safety‎ History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving ‎reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might ‎affect the interpretation of the results of the study or render the patient at high risk for treatment complications‎ Participation as a patient in any clinical study within the 12 weeks prior to the screening visit‎ The use of long-acting steroids, either systemically or intraocularly, in the six months prior to screening visit‎ Any history of allergy to povidone iodine‎ Females who are pregnant, breastfeeding, planning to become pregnant during the study period, unwilling to ‎practice adequate contraception throughout the study and for at least 60 days following the last dose of study ‎medication ‏History of stroke, myocardial infarction or uncontrolled hypertension (blood pressure >160/100 despite receiving ‎medical treatment) for less than three months from the date of the Screening visit‎ Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, ‎pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders‎
Age
From 55 years old to 80 years old
Gender
Both
Phase
3
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 168
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization plan of the patients will be carried out centrally using an R-CRAN software ‎version 3.2.3. Blocks (with the size 2 or 4) will be made using permuted block randomization for ‎a total of 168 patients (1:1 allocation ratio). After the randomization procedure, a code will be ‎allocated to each patient that will be used as a patient identifier throughout the study. The assigned ‎code will be denoted by 4 initials (corresponding to the first two letters of the first name, first two ‎letters of surname) and 3 numbers (center code). Moreover, the described code is followed by ‎study unique identification code consisting of first three letters of the generic name of the ‎investigational product (AFL), and three numbers (corresponding to the randomization number), ‎e.g. ABCD001AFL-001. The randomization number will be assigned in a consecutive way.‎
Blinding (investigator's opinion)
Double blinded
Blinding description
Both Aflibercept products used in the study will be entirely indistinguishable for patients and ‎health care providers since they are identical in shape, size, label, and color. The container of the ‎drugs will be labeled using identical Labels so they will be impossible to differentiation. Patients ‎groups and their drugs will not be disclosed to investigators. After that, the patient signed ‎Informed consent and considered to be eligible base on‏ ‏the inclusion and exclusion criteria; he or ‎she will be allocated to one of each group. ‎‏ ‏The investigator will not be informed of randomization, ‎and all the drug codes will be placed in an opaque pocket inside each sites trial Master file. Data ‎analyzers will not be informed of the patients' grouping.‎
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
The Ethics Committee of Tehran University of Medical Sciences
Street address
Qods St., Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2019-05-07, 1398/02/17
Ethics committee reference number
‎ IR.TUMS.VCR.REC.1398.116 ‎

Health conditions studied

1

Description of health condition studied
Neovascular age-related macular Degeneration
ICD-10 code
H35.32
ICD-10 code description
Exudative age-related macular degeneration

Primary outcomes

1

Description
The proportion of patients achieving maintaining vision (losing<15‎‏ ‏letter on ETDRS chart) at week 52, in ‎comparison to visit 0.‎
Timepoint
baseline visit, 52 weeks after first intervention
Method of measurement
Tumbling-E ETDRS chart

Secondary outcomes

1

Description
Mean changes in the Best-Corrected Visual Acuity Index measured with ETDRS chart from visit 0 to week 52‎
Timepoint
baseline visit and 52 weeks after first intervention
Method of measurement
Tumbling E ETDRS chart

2

Description
The percentage of patients who have increase of ≥15‎‏ ‏score in ETDRS at week 52
Timepoint
52 weeks after first intervention
Method of measurement
Tumbling E ETDRS chart

3

Description
The mean change in National Eye Institute Visual Function Questionnaire (NEI VFQ-25) at week 52 compared to ‎the visit 0.‎
Timepoint
Baseline Visit and 52 weeks after first intervention
Method of measurement
NEI VFQ-25

4

Description
Mean changes in central retinal thickness based on structural OCT at week 52 compared to the screening visit‎
Timepoint
baseline visit and 52 weeks after first intervention
Method of measurement
Optical Coherence Tumography (OCT)

5

Description
The percentage of patients without intra-retinal fluid and subretinal fluid based on structural OCT at week 52‎
Timepoint
52 weeks after first intervention
Method of measurement
Optical Coherence tumography

6

Description
Systemic and Ophthalmic Adverse events (AEs) and adverse drug reactions (ADR)‎‏ ‏‎– at ‎screening, visit 1 and all the follow-up visits until week 52‎
Timepoint
All of the studu visits
Method of measurement
Physical examination

7

Description
Comparing immunogenicity of two products and evaluating antibody formation- at ‎screening visit, week 24 and week 52.‎
Timepoint
screening visit, 24 weeks, and 52 weeks after first intervention
Method of measurement
ELISA Assay

8

Description
Evaluation of blood pressure- at screening visit and week 52‎
Timepoint
Screening Visit, 52 weeks after first intervention
Method of measurement
blood pressure meter

9

Description
Clinical laboratory testing for systemic safety, including liver and kidney functions, ‎complete blood count and clinical bio-chemistries- at regular intervals‎
Timepoint
screening visit, 12 weeks and 52 weeks after first intervention
Method of measurement
Lab test

10

Description
Changes in physical examination findings- at screening visit and week 52‎
Timepoint
Screening Visit, and 52 weeks after first intervention
Method of measurement
Physical examination

Intervention groups

1

Description
Aflibercept (CinnaGen Co, Iran) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 ‎injections, followed by 2 mg every 8 weeks (every two months) Until week 48 of study
Category
Treatment - Drugs

2

Description
Eylea (Regeneron, USA) 2 mg (0.05 mL) by intravitreal injection every 4 weeks (Monthly) for the first 3 injections, ‎followed by 2 mg every 8 weeks (every two months) Until week 48 of study.‎
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Farabi Hospital
Full name of responsible person
Dr. Reza Karkhane
Street address
Kargar Jonobi, District 11, Tehran
City
Tehran
Province
Tehran
Postal code
1336616351
Phone
+98 21 5540 0003
Email
farabih@tums.ac.ir
Web page address
http://farabih.tums.ac.ir/

2

Recruitment center
Name of recruitment center
Labafinezhad Hospital
Full name of responsible person
Dr. Hamid Ahmadieh
Street address
Pasdaran St, District 4, Tehran
City
Tehran
Province
Tehran
Postal code
1666663111
Phone
+98 21 23601
Email
labafi@gmail.com
Web page address
http://labafinejad.tamin.ir

3

Recruitment center
Name of recruitment center
Rasool Akram Hospital
Full name of responsible person
Dr. Khalil Ghasemi Falavarjani
Street address
SatarKhan St., District 2, Tehran
City
Tehran
Province
Tehran
Postal code
1445613131
Phone
+98 21 6651 5001
Email
hrmc@iums.ac.ir
Web page address
http://hrmc.iums.ac.ir/

4

Recruitment center
Name of recruitment center
Khalili Hospital
Full name of responsible person
Dr. Hossein Ashraf
Street address
Khalili St., Shiraz
City
Shiraz
Province
Fars
Postal code
14336-71348
Phone
+98 71 3629 1470
Email
khalili@sums.ac.ir
Web page address
https://khalili.sums.ac.ir

5

Recruitment center
Name of recruitment center
Khatamolanbia Hospital
Full name of responsible person
Dr. Naser Shoeybi
Street address
Qarani Ave., Mashhad
City
Mashhad
Province
Razavi Khorasan
Postal code
45986520
Phone
+98 51 3728 1401
Email
info@khatamhospital.org
Web page address
https://www.khatamhospital.org/

6

Recruitment center
Name of recruitment center
Imam Hossein Hospital
Full name of responsible person
Dr. Alireza Ramazni, Dr. Homayoun Nikkhah
Street address
shahid Madani St., Tehran
City
Tehran
Province
Tehran
Postal code
321654646
Phone
+98 21 7755 8001
Email
info@ehmc.ir
Web page address
https://ehmc.ir

7

Recruitment center
Name of recruitment center
Torfeh Hospital
Full name of responsible person
Dr. Saeed Hosseini
Street address
Ebn Sina St,. District 12, Tehran
City
Tehran
Province
Tehran
Postal code
65414656
Phone
+98 21 7762 6550
Email
TorfeHospital@sbmu.ac.ir
Web page address
http://tomc.sbmu.ac.ir/

8

Recruitment center
Name of recruitment center
Noor eye Hospital and clinic
Full name of responsible person
Dr. Hooshang Faghihi
Street address
Esfandyar Blvd, Valiasr St., Tehran
City
Tehran
Province
Tehran
Postal code
54646316546
Phone
+98 21 8240 1645
Email
info@noorvision.com
Web page address
https://www.noorvision.com/

9

Recruitment center
Name of recruitment center
Razi Eye Center
Full name of responsible person
Dr. Alireza Lasheie
Street address
South Gandhi St., Vanaq Square, Tehran
City
Tehran
Province
Tehran
Postal code
36465213
Phone
+98 21 81034
Email
info@razieyeclinic.com
Web page address
http://razieyeclinic.com

10

Recruitment center
Name of recruitment center
Vanak Eye Surgury Center
Full name of responsible person
Dr. Ahmad Mirshahi
Street address
No 50, Haqani Highway
City
Tehran
Province
Tehran
Postal code
5464654164
Phone
+98 21 8887 4394
Email
info@vesc.ir
Web page address
http://www.vesc.ir/

11

Recruitment center
Name of recruitment center
Negaah eye hospital
Full name of responsible person
Dr. Mahdi Modareszadeh
Street address
Ketabi St,. Shariati St,. Tehran
City
Tehran
Province
Tehran
Postal code
1544914599
Phone
+98 21 23555
Email
info@Negaheyehospital.com
Web page address
http://negaheyehospital.com

12

Recruitment center
Name of recruitment center
Central eye clinic
Full name of responsible person
Dr. Khalil Ghasemi Falavarjani
Street address
Shahid St,. Vanaq Square, Valiasr St,.
City
Tehran
Province
Tehran
Postal code
5465465
Phone
+98 21 8867 7652
Email
hrmc@iums.ac.ir
Web page address

13

Recruitment center
Name of recruitment center
Amir Al Mo'menin Educational Remedial & Research Center
Full name of responsible person
Dr. Hassan Behboodi, Dr. Yousef Alizadeh
Street address
17 th Shahrivar, Imam Khomeini St., Rasht
City
Rasht
Province
Guilan
Postal code
1113351313
Phone
+98 13 3323 8306
Email
amiralmomenin@gums.ac.ir
Web page address
http://www.gums.ac.ir/amir/

14

Recruitment center
Name of recruitment center
Feiz Hospital
Full name of responsible person
Dr. Farhad Fazel Najafabadi, Dr. Mohammadreza Akhlaghi
Street address
Modares St., Isfehan
City
Isfehan
Province
Isfehan
Postal code
641030132
Phone
+98 31 3303 3460
Email
info@feiz.mui.ac.ir
Web page address
http://feiz.mui.ac.ir/

15

Recruitment center
Name of recruitment center
Imam Khomeini Hospital
Full name of responsible person
Dr. Pezhvak Azadi, Dr. Hamid Aryaeitabar, Dr. leila Rezaei
Street address
Naqlieh St,. Kermanshah
City
Kermanshah
Province
Kermanshah
Postal code
6718743161
Phone
+98 83 3728 3602
Email
ihosp@kums.ac.ir
Web page address
https://imamkhomaini.kums.ac.ir/

16

Recruitment center
Name of recruitment center
Imam Khomeini Hospital
Full name of responsible person
Dr. Feridoon Farahi, Dr. Mostafa Feghhi, Dr. Ali Kasiri
Street address
Azadegan St., Ahwaz
City
Ahwaz
Province
Khouzestan
Postal code
6193673111
Phone
+98 61 3222 2114
Email
himam@ajums.ac.ir
Web page address
http://himam.ajums.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?
Yes
Title of funding source
CinnaGen company
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
Orchid Pharmed Co.
Full name of responsible person
Dr. Somayeh Amini
Position
medical department manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Atar S.q, Atar St., Vanak S.q, Valiasr St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
19947766411
Phone
+98 21 8808 8821
Email
amini.s@orchidpharmed.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Reza Karkhane
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Ophthalmology
Street address
Farabi Hospital, Kargar Jonoobi St., District 11
City
Tehran
Province
Tehran
Postal code
1336616351
Phone
+98 21 5540 0003
Email
Karkhane@tums.ac.ir

Person responsible for updating data

Contact
Name of organization / entity
شرکت ارکیدفارمد
Full name of responsible person
Dr. Nassim Anjidani
Position
Pharmacist, Clinical Trial Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Atar S.q, Atar St., Vanak S.q, Valiasr St., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
19947766411
Phone
+98 21 8808 8821
Email
Anjidani.N@orchidpharmed.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be 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
Not applicable
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Loading...