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CTRI Number  CTRI/2017/11/010451 [Registered on: 10/11/2017] Trial Registered Prospectively
Last Modified On: 04/04/2019
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Study of suprachoroidal CLS-TA with Intravitreal Aflibercept in Subjects with Retinal Vein Occlusion 
Scientific Title of Study   SAPPHIRE: A randomized, Masked, controlled trial to study the safety and efficacy of suprachoroidal CLS-TA in conjunction with Intravitreal Aflibercept in Subjects with Retinal Vein Occlusion 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CLS1003-301 Amendment 1 31 Mar 2017  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Saurendra Das  
Designation  Executive Director 
Affiliation  Excel Life Sciences Pvt Ltd 
Address  Excel Life Sciences Pvt. Ltd, Assotech Business Cresterra, Tower-2, 9th Floor, Unit-909-913, Plot No.22, Sector-135, NOIDA 201301 India

Gautam Buddha Nagar
UTTAR PRADESH
201301
India 
Phone  01206280200  
Fax  01206280200  
Email  sauren@excellifesciences.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Dr Saurendra Das  
Designation  Executive Director 
Affiliation  Excel Life Sciences Pvt Ltd 
Address  Excel Life Sciences Pvt. Ltd, Assotech Business Cresterra, Tower-2, 9th Floor, Unit-909-913, Plot No.22, Sector-135, NOIDA 201301 India

Gautam Buddha Nagar
UTTAR PRADESH
201301
India 
Phone  01206280200  
Fax  01206280200  
Email  sauren@excellifesciences.com  
 
Source of Monetary or Material Support  
Clearside Biomedical, Inc., 900 North Point Parkway, Suite 200 Alpharetta, GA 30005, USA  
 
Primary Sponsor  
Name  Clearside Biomedical Inc  
Address  900 North Point Parkway, Suite 200 Alpharetta, GA 30005, USA  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Australia
Canada
Czech Republic
Germany
Hungary
India
Israel
Italy
Philippines
Slovakia
Spain
Taiwan
United Kingdom
United States of America
Austria
Denmark
Poland
Portugal
Other  
Sites of Study
Modification(s)  
No of Sites = 12  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr V R Saravanan  Aravind Eye Hospital   Avinashi Road, Coimbatore - 641 014, Tamilnadu, India
Coimbatore
TAMIL NADU 
9790697555

saravananvr@gmail.com 
Dr Naresh B Kannan  Aravind Eye Hospital and Post Graduate Institute of Ophthalmology  Anna Nagar Main Road, Kuruvikaran Salai, Anna Nagar, Sathamangalam, Madurai, Tamil Nadu- 625020, India
Madurai
TAMIL NADU 
09443490920

cauveryeye@gmail.com 
Dr Santanu Mandal  Disha Eye Hospital Private Limited  88 (63A) Ghoshpara Road, Barrackpore, Kolkata- 700120, West Bengal, India
Kolkata
WEST BENGAL 
09830161959

dr.santanumandal@yahoo.com 
Dr Atul Kumar  Dr. Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences  Ansari Nagar, New Delhi-110029, India
New Delhi
DELHI 
01126588919

atul56kumar@yahoo.com 
Dr Shalini Singh  Dr. Shroffs Charity Eye Hospital  5027, Kedarnath Road, Beside Vani Prakashan, Daryaganj, New Delhi
New Delhi
DELHI 
9958927755

shalini.singh@sceh.net 
Dr Divya Balakrishnan  L.V. Prasad Eye Institute  Department of Retina, Kallam Anji Reddy Campus, L.V. Prasad Marg, Banjara Hills, Hyderabad - 500034, Andhra Pradesh, India
Hyderabad
ANDHRA PRADESH 
09581447997

divya@lvpei.org 
Dr Jignesh Gosai  M&J Western Regional Institute of Ophthalmology  Oculoplasty Department, A-2 , Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat- 380016, India
Ahmadabad
GUJARAT 
09824321195

dr_jigneshgosai@hotmail.com 
Dr Sucheta Kulkarni  PBMA’s H. V. Desai Eye Hospital  Retina Department, S. No. 93, Tarawade Vasti, Mohammadwadi Road, Hadapsar, Pune- 411060, Maharashtra, India
Pune
MAHARASHTRA 
02026970043

drsucheta.kulkarni@gmail.com 
Dr Bibhuti Prassan Sinha  Regional Institute of Ophthalmology  Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna-800014
Patna
BIHAR 
9470017777

bibhuti13@gmail.com 
Dr Rahul Shroff  Shroff Eye Hospital & Lasik Centre  222, S. V. Road, Near Suburbia Movie Theatre, Bandra (W), Mumbai– 400050, Maharashtra, India
Mumbai
MAHARASHTRA 
02266949876

rahul@shroffeye.org 
Dr Ronel Soibam  Sri Sankaradeva Nethralaya   Department of Retina, 96, Basistha Road, Beltola, Guwahati- 781028, Assam, India
Kamrup
ASSAM 
9957184140

ronelsoibam@yahoo.co.in 
Dr Saroj Sahdev  T. N. Medical College and B. Y. L. Nair Charitable Hospital  Department of Ophthalmology, Dr. A. L. Nair Road, Mumbai-400008, Maharashtra, India
Mumbai
MAHARASHTRA 
02223027647

sisahdev@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
B.J. Medical College & Civil Hospital, Ahmedabad-380016, India  Approved 
Dr. Shroffs Charity Eye Hospital Ethics Committee at Dr. Shroffs Charity eye hospital 5027 Kedar nath Road Daryaganj New Delhi-11002  Approved 
Ethics Committee Situated at L. V. Prasad Eye institute Kallam Anji Reddy Campus L. V. Prasad marg, Road No. 2 Banjara Hills Hyderabad-500034, India  Approved 
Ethics Committee situated at Shroff eye hospital 2nd Floor 222 SV Road near Suburbia Movie theatre bandra West Mumbai- 400050, Maharashtra, India  Approved 
Institute Ethics Committee, All India Institute of Medical Sciences, Ansari Nagar, New Delhi -110029, India  Approved 
Institutional Ethics Committee Aravind Medical Research Foundation, 1, Anna Nagar, Madurai-625 020, Tamil Nadu  Approved 
Institutional Ethics Committee of Topiwala National Medical College and BYL Nair Charitable Hospital G Building Ground Floor, Dr A.L Nair Road, Mumbai Central ,Mumbai-400008  Approved 
Institutional Ethics Committee situated at Disha Eye Hospital Pvt Ltd 88 (63A) Ghosh Para road Barrackpore Kolkata-700120, West bengal, India  Approved 
Institutional Ethics Committee, PBMS H.V Desai Eye Hospital, S.No.93 Taravade Vasti, Mohammadwadi, Hadapsar Pune-411060 Maharashtra, India  Approved 
Institutional Ethics Committee,Indira Gandhi Institue of Medical Sciences IGMS Sheikhpura Patna-800014 Bihar India  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: H348||Other retinal vascular occlusions,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Aflibercept  IntraVitral aflibercept (2 mg/0.05 mL)once a month 
Intervention  CLS-TA  SupraChoroidal CLS-TA (4 mg/100 micro litre) once in 3 months  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1. Has a clinical diagnosis of RVO in the study eye within less than or equal to 9 months screening;
2. Has a CST of greater than or equal to 300 micro metre in the study eye as measured by spectral-domain optical
coherence tomography (SD-OCT) with or without intraretinal or subretinal fluid and
confirmed by the central reading center (CRC);
3. Has an ETDRS BCVA score of greater than or equal to 20 letters read and less than or equal to 70 letters read in the study eye;
4. Is naïve to local pharmacologic treatment for RVO in the study eye;
5. Is at least 18 years of age, understands the language of the informed consent and is willing and able to provide written informed consent before any study procedures, and is willing to comply with the instructions and attend all scheduled study visits. 
 
ExclusionCriteria 
Details  1. Has ME with etiology other than RVO;
2. Has, in the study eye, used any topical ocular corticosteroid in the 10 days before
treatment at Visit 2 (Day 0); has at any time received any intraocular or periocular corticosteroid injection, an OZURDEX® implant, a RETISERT® implant, or an ILUVIEN® implant;
3. Has evidence of or history of any ophthalmic condition in the study eye that may have an
associated neovascularization or edema component including, but not limited to,
age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema
(DME), retinal detachment, central serous chorioretinopathy, scleritis, optic neuropathy,
or retinitis pigmentosa;
4. Has a history of rubeosis irides or other neovascularization in the study eye; any active
vitreous hemorrhage in the study eye within the last 90 days;
5. Has a history of any vitreoretinal surgery (scleral buckle placement, pars plana
vitrectomy, retrieval of dropped nucleus or intraocular lens, sheathotomy) ever in the
study eye or any ocular surgery in the 3 months before randomization. Prior cataract extraction or Yttrium-Aluminum-Garnet (YAG) laser capsulotomy is allowed but must have been performed at least 3 months before Visit 2 (Day 0);
6. Has a history of an ocular procedure or condition in the study eye within the 3 months
before randomization that, in the Investigator’s opinion, could compromise globe or retinal integrity (eg, staphyloma, high myopia, predisposition to scleral thinning);
7. An ocular condition in the study eye that, in the opinion of the Investigator, would put the subject at risk due to study treatment or procedures (eg, active ocular infection, history of a SC hemorrhage, chalazion, significant blepharitis);
8. Has scarring from laser photocoagulation in the study eye that would compromise visual
acuity;
9. Has had more than 3 macular laser photocoagulation treatments; or has had photocoagulation or cryotherapy in the study eye within the 6 months before Visit 2 (Day 0);
10. Has significant media opacity precluding evaluation of retina and vitreous in the study
eye. This includes cataract that is felt to be a major contributor to reduced visual acuity
and/or likely to undergo surgical repair within 3 months of randomization;
11. History of glaucoma, optic nerve head change consistent with glaucoma damage; or
ocular hypertension in the study eye requiring more than one medication;
12. Has a IOP > 21 mmHg in the study eye at Visit 1 (Day -30 to -1); subjects are not
excluded if IOP is < 22 mmHg in the study eye with no more than 1 IOP-lowering
medication as long as there is no history of glaucoma and the subject has a normal optic
nerve and no evidence of visual field loss;
13. Has a history of glaucoma surgery (filtration surgery/trabeculectomy or tube shunt) in the study eye; has a history of laser trabeculoplasty or MIGs surgery in the study eye;
14. Has a history of clinically significant IOP elevation in response to corticosteroid
treatment (“steroid responder”);
General Exclusion Criteria
Individuals are ineligible for participation in this study if he/she meet the following criteria:
15. Is a female subject who is pregnant, lactating or planning a pregnancy or is a female subject of childbearing potential who does not agree to submit to a pregnancy test at
Screening; Females of childbearing potential must agree to use an acceptable method of
contraception throughout participation in the study. Acceptable methods of contraception
include double barrier methods (condom with spermicide or diaphragm with spermicide),
hormonal methods (oral contraceptives; implantable, transdermal, or injectable
contraceptives), or an intrauterine contraceptive device with a documented failure rate of less than 1% per year. Abstinence may be considered an acceptable method of
contraception at the discretion of the Investigator, but the subject must agree to use one of the acceptable birth control methods if she becomes sexually active;
16. Has any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study (eg, infection, uncontrolled elevated blood pressure,cardiovascular disease, poor glycemic control) or put the subject at risk due to study treatment or procedures; NOTE: Uncontrolled BP at screening may be treated before Visit 2;
17. Has a myocardial infarction or stroke within 90 days of treatment;
18. Has a likely need for hospitalization or surgery within the study period, including planned elective surgery or hospitalization;
19. Has a known hypersensitivity to any component of the formulation of TA,aflibercept,
fluorescein, topical anesthetics, or the antiseptic used to prepare the eye for injection according to the Investigator’s standard practice;
20. Is currently enrolled in an investigational drug or device study or has used an
investigational drug within 30 days of entry into this study or participated in an ocular
device study in the last 90 days.
21. History of any inflammatory or other medical condition that the investigator might
reasonably anticipate will require treatment with high-dose corticosteroids (more than
10mg/day oral prednisone or the equivalent) for more than 14 days. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
To demonstrate that suprachoroidal (SC) CLS-TA administered in conjunction with intravitreal
(IVT) aflibercept is superior to IVT aflibercept alone in the proportion of subjects demonstrating more than or equal to 15 letters improvement in best corrected visual acuity (BCVA) two months after Baseline 
Baseline to 8 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
1 To determine the effect of SC CLS-TA administered in conjunction with IVT aflibercept on mean
change from Baseline in BCVA
2 To determine the effect of SC CLS-TA administered in conjunction with IVT aflibercept on mean
change from Baseline in central subfield thickness 
Baseline to 24 weeks 
 
Target Sample Size   Total Sample Size="460"
Sample Size from India="65" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  
12/02/2018 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  15/02/2017 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="5"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Other (Terminated) 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details   Patel SR, Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye, Invest Ophthalmol Vis Sci. 2012 Jul 1;53(8):4433-41 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   This is a randomized, masked, controlled trial to study the safety and efficacy of suprachoroidal CLS-TA in conjunction with intravitreal aflibercept in subjects with retinal vein occlusion. The quaified subjects will be divided into two groups. Active group will receive IVT Aflibercept + CLS-TA
Control group will receive IVT Aflibercept + CLS-TA Sham
 
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