Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201701001940111 Date of Approval: 25/12/2016
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Safety of ziv-aflibercept in retinal diseases in a Ghanaian population.
Official scientific title Safety of ziv-aflibercept in retinal diseases in a Ghanaian population.
Brief summary describing the background and objectives of the trial Retinal vascular diseases are a significant cause of visual loss world-wide, including Ghana. Anti-vascular endothelial growth factor (anti-VEGF) such as aflibercept, ranibizumab and bevacizumab have become the standard of care for diabetic macular edema (DME), macular edema (ME) following retinal vein occlusions (RVO), and neovascular age related macular degeneration(nvAMD). Aflibercept has been approved by the USA Food and Drug Administration (FDA) for the treatment of DME, nvAMD, and ME following RVO. The recommended dose of intravitreal aflibercept is 2mg in 0.05ml administered monthly or initial monthly injections for the first 3 months followed by 2 monthly injections. Aflibercept is highly expensive (USD1850 per dose) and not available in many developing countries including Ghana. Ziv-aflibercept, a molecule structurally identical to aflibercept but differs due to its formulation with hyper-osmolality has been approved by the USA FDA for the treatment of metastatic colorectal cancers. Ziv-aflibercept, used off-label, has been found to be safe in patients with DME and nvAMD in phase 1 trials at a dose of 1.25mg in 0.05ml. The cost of compounded ziv-aflibercept is much reduced to USD 67 per dose. The 1.25mg dose of ziv-aflibercept is below that recommended for intravitreal injections of aflibercept. However, to the best of our knowledge, there are no data available on the safety of 2mg of ziv-aflibercept, although in vitro studies indicate that it is safe. Furthermore, there is no data on the intravitreal administration of ziv-aflibercept in the Ghanaian population to date. Specific Objectives: 1.To determine the safety of intravitreal injections of ziv-aflibercept at 4 and 12 weeks in a Ghanaian population. 2.To measure the visual outcome of treatment with 1.25mg and 2mg ziv-aflibercept in eyes with DME, nvAMD,and ME secondary to RVO at 12 weeks.3.To measure the anatomic changes using SD-OCT in eyes with DME, nvAMD and ME secondary to RVO at 12 weeks.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied diabetic macula edema,,Eye Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 01/02/2017
Actual trial start date 01/02/2017
Anticipated date of last follow up 31/05/2017
Actual Last follow-up date 31/05/2017
Anticipated target sample size (number of participants) 20
Actual target sample size (number of participants) 20
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised picking 2 labelled cards from an envelope by an individual independent of the study investigators (EA) but the treatment is concealed to the patients.A certified physician (unmasked) will give the intravitreal injection. The examining physician(IZB) and an independent assessor of anatomic response(WMA) will be masked to the treatment doses. Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group intravitreal ziv-aflibercept 2mg monthly injection 3 months intravitreal injection will be done using a sterile technique. Topical proparacaine and 5% povidone iodine will be instilled into the conjunctival cul-de sac and periocular skin, eyelids and lashes will be cleaned using 10% povidone iodine. The eye will be draped and the injection given into the mid vitreous cavity 4 mm or 3.5mm posterior to the limbus in phakic and pseudophakic eyes respectively 10
Control Group intravitreal ziv-aflibercept 1.25mg 1.25mg/0.05ml monthly 3 months intravitreal injection will be done using a sterile technique. Topical proparacaine and 5% povidone iodine will be instilled into the conjunctival cul-de sac and periocular skin, eyelids and lashes will be cleaned using 10% povidone iodine. The eye will be draped and the injection given into the mid vitreous cavity 4 mm or 3.5mm posterior to the limbus in phakic and pseudophakic eyes respectively 10 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age 18 years or older Meets diagnostic criteria for DM, RVO and active nvAMD (Appendix I) Treatment naïve Understands and willing to sign consent form Able to comply with clinic visits Centre involving ME in patients with diabetes mellitus and RVO with retinal thickness >300um using SD- OCT BCVA of 6/12 or worse Glaucoma or raised intraocular pressure (>21mmHg) Intraocular surgery within 3 months in the study eye History of uveitis Pregnant or breastfeeding mother Renal failure on dialysis or had kidney transplant Allergy to active drug or excipients Cardiovascular events such as myocardial infarction or CVA Eye infections such blepharitis, dacryocystitis, conjunctivitis or keratitis. Unwilling to sign consent form or to come for follow up visits Myopia ¿-6.0 Dioptres 18 Year(s) 85 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 04/11/2016 Scientific and Technical Committee of Korle-Bu Teaching Hospital
Ethics Committee Address
Street address City Postal code Country
Director of Medical Affairs office, Korle-Bu Teaching Hospital Accra 4236 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome safety of intravitreal ziv-aflibercept includingincidence of raised intraocular pressure, cataract progression, intraocular inflammation and endophthalmitis 30 minutes after initial njection 1 day after initial injection 7 days after initial injection 4 weeks after initial injection
Secondary Outcome ocular and systemic safety parameters, change in BCVA (ETDRS letters), central subfield foveal thickness (CSFT) and central retinal thickness (CRT) using SD-OCT 4 weeks 12 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
retina OPD, Eye Centre, Korle Bu Teaching Hospital Slater avenue, Korle-Bu Teaching Hospital Accra 4236 Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Eye Centre Korle-Bu Teaching Hospital Slater avenue, Korle-Bu Teaching Hospital Accra 4236 Ghana
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Imoro Zeba braimah Alexander Street, Korle-Bu Teaching Hopital Accra 4236 Ghana Commercial Sector/Industry
Primary Sponsor Eye Centre, Korle-Bu Teaching Hospital Slater Avenue, Korle-Bu Teaching Hospital Accra 4236 Ghana Hospital
COLLABORATORS
Name Street address City Postal code Country
Akafo Stephen Slater Avenue, Korle-Bu Teaching Hospital Accra 4236 Ghana
Kwesi N. Amissah-Arthur Slater Avenue, Korle-Bu Teaching Hospital Accra 4236 Ghana
Winfried M. Amoaku Academic Ophthalmology, DCN, Faculty of Medicine and Health Sciences, University of Nottingham Nottingham United Kingdom
Ernest Kenu 4. Department of Medicine, School of Medicine and Dentistry, Korle-Bu Accra 4236 Ghana
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Imoro Zeba Braimah zebimoro2000@yahoo.com +233206301353 Alexander St, Block 3B, Drs Flats, Korle-Bu
City Postal code Country Position/Affiliation
Accra 4236 Ghana Lecturer School Medicine, Dentistry; Consult Ophthalmologist Korle-Bu Teaching Hosp
Role Name Email Phone Street address
Public Enquiries Benjamin Abaidoo benjamin_abaidoo@yahoo.com +233 27 781 8746 Department of surgery (Eye), School of Medicine and Dentistry, University of Ghana
City Postal code Country Position/Affiliation
Accra 4236 Ghana Senior research Assistant, School of Medicine and Dentistry, University of Ghana.
Role Name Email Phone Street address
Scientific Enquiries Imoro Zeba Braimah zebaimoro2000@yahoo.com +233206301353 Alexander St, Block 3B, Drs Flats, Korle-Bu
City Postal code Country Position/Affiliation
Accra 4236 Ghana Lecturer School Medicine Dentistry; Consul Ophthalmologist Korle-Bu Teaching Hosp
REPORTING
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