CIGB-247-V vaccine in Age-Related Macular Degeneration, phase I-II randomized.

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Acronym of Public Title:

CELIMAR Study

Scientific title:

Use of the CIGB-247-V vaccine candidate in the treatment of Age-Related Macular Degeneration.

Secondary indentifying numbers:

IG/CIGB-247I/DM/1301

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB), in Havana.

Source(s) of monetary or material support:

Center for Genetic Engineering and Biotechnology (CIGB), Havana. Ministry of Public Health, CUBA.

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

05-010-14-BA (Procedure code), July 23, 2014. (In process)

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Rafael

Last name:

Gonzalez Diaz

Medical Specialty :

2nd Degree Specialist in Ophthalmology.

Affiliation:

Cuban Institute of Ophthalmology "Ramóo Pando Ferrer".

Postal address:

Calle 76 # 3104 e/ 31 y 41, Marianao

City:

Havana

País:

Cuba

Zip Code:

11400

Telephone:

+53-72654838

Email address:

rafaele@infomed.sld.cu [1]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana, Center of Medical and Surgical Research (CIMEQ), Isis Montesinos Alvarez, MD, 1st Grade Specialist in Ophthalmology.

Research ethics committees:

Cuban Institute of Ophthalmology "Ramon Pando Ferrer", May 30, 2014.

Center of Medical and Surgical Research, July 7, 2014.

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

01/03/2015

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Age-Related Macular Degeneration.

Intervention(s):

Group I (Control A): Intravitreal treatment with antibody Bevacizumab (Avastin®) (monthly scheme for one year). Group II (Control B): Intravitreal treatment with antibody Bevacizumab (Avastin®) (monthly schedule for 3 months and then as ophthalmologic clinical requirement). Group III (Study): hVEGFKDR- p64K antigen (400 ug) + adjuvant NAcGM3 / VSSPs (200 ug) applied subcutaneously in the deltoid region + intravitreal treatment with antibody Bevacizumab (Avastin®) (monthly schedule for 3 months and then as required ophthalmological) clinician. Group IV (Study): antigen p64K-hVEGFKDR- (800 ug) + adjuvant NAcGM3 / VSSPs (200 ug) applied subcutaneously in the deltoid region + Intravitreal treatment with antibody Bevacizumab (Avastin®) (monthly schedule for 3 months and then as required ophthalmological) clinician.

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Clinical Adverse Events (Occurrence of EA (Yes, No). EA Description (name of event). EA intensity (mild, moderate, severe)). Measuring time: a) groups I and II: at baseline and monthly for 12 months; b) groups III and IV: at baseline, one week after each of the first 8 immunizations and thereafter at a rate monthly throughout the study. Laboratory (numerical values of hematological and biochemical tests). Measuring time: at baseline and at months 3, 6, 9 and 12. Intravitreal Injection of Bevacizumab, in addition to the three basic administered, necessary to maintain or improve the anatomical and functional parameters chosen (number of shots). Measuring time: a year of starting treatment.

Key secondary outcomes:

Signs of activity (presence of hemorrhage, cystoid macular edema, subretinal fluid and exudation). Measuring time: monthly, every ophthalmologic evaluation. Type of injury (fluorescein / indocyanine green angiography: predominantly classic, minimally classic, occult, and retinal angiomatous proliferation polypoid choroidal vasculopathy). Measuring time: 85 days and one year after starting treatment. Activity injury (fluorescein / indocyanine green angiography: active lesions, no active lesion). Measuring time: 85 days and one year after starting treatment. Location fluid (intra-retinal edema, subretinal fluid, serous epithelial detachment). Measuring time: monthly, every ophthalmologic evaluation. Number of lines (lets you know the answer in visual acuity, considering 3 categories: a) Improved if gained 3 or more lines; b) Stable, whether you win or lose less than 3 lines; c) Worsened, if you miss 3 or more lines). Measuring time: monthly, every ophthalmologic evaluation. Central macular thickness (in microns as macular map, optical coherence tomography). Measuring time: monthly, every ophthalmologic evaluation. Central macular thickness (single cut, optical coherence tomography). Measuring time: monthly, every ophthalmologic evaluation. Immune response (presence or absence of immune response to the vaccine, as measured by specific IgG titers in serum VEGF vaccinated patients of antibodies against time before vaccination, and negative and positive controls reference). Measuring time (only for groups III and IV): 29, 78 and 85, and months 4, 5, 6, 7, 8, 9, 10, 11 and 12 after the start of vaccination.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

50 years

Maximum age:

70 years

Inclusion criteria:

1) Age between 50-70 years inclusive. 2) Patients with choroidal neovascularization (CNV) secondary to macular degeneration (ARMD) subfoveal including retinal angiomatous proliferation (RAP) or polypoidal choroidal vasculopathy (VCP). 3) foveal center directly affected by CNV, fluid or blood derivative thereof. 4) area greater than 50% of the lesion, except in cases with serous retinal pigment epithelium NVC. 5) Best corrected visual acuity (BCVA) ≥ 25 ETDRS letters primer. 6) Voluntary patient by signing the informed consent.

Exclusion criteria:

1) Presence of any of the following disorders / eye procederes: a) atrophy, bleeding or scarring of more than 50% of the lesion, b) subfoveal subretinal hemorrhage over an area of the disc, c) pigment epithelium tear, d) pretreatment on the eye: laser photocoagulation, photodynamic therapy, peri- or intraocular triamcinolone, e) after injection of anti-VEGF antibodies in either eye, f) cataract surgery in the past 3 months, g) media opacity, h) waterfall (which prevents adequate visualization of the fund), uveitis or glaucoma uncontrolled i) pars plana vitrectomy (PPV). 2) Patients who have received any anti-angiogenic treatment, by any means, in the last 3 months (intravitreal treatment of AMD as Lucentis [ranibizumab] Eylea® [Aflibercept; Regeneron] and / or Bevacizumab [Avastin ®], or systemic treatment of cancer). 3) Major surgery in the last 28 days. 4) history of stroke, acute myocardial infarction or other significant vascular impairment (Example: DVT) in the last 6 months. 5) Chronic diseases unbalanced (hypertension, diabetes mellitus, chronic renal failure, heart failure, hyperthyroidism, epilepsy). 6) referenced immunosuppressive disease, immunosuppressive current intake / immunomodulatory drugs. 7) history of autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, etc.) and severe allergic history (urticaria, dermatitis, bronchitis and persistent asthma). 8) History of allergy to any ingredient of the vaccine study, iodine, or any dye used in diagnostic techniques. 9) moderate or severe systemic infections that interfere with patient evaluation. 10) Mental incapacity to issue clear consent and act accordingly to the study.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

1-2

Target sample size:

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Francisco

Last Name:

Hernandez-Bernal

Specialty:

2nd Degree Specialist in Hygiene and Epidemiology.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

País:

Cuba

Zip Code:

6162

Telephone:

+537-2085887, 2087465

Email :

hernandez.bernal@cigb.edu.cu [2]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Francisco

Last Name:

Hernandez-Bernal

Specialty:

2nd Degree Specialist in Hygiene and Epidemiology.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

País:

Cuba

Zip Code:

6162

Telephone:

+537 2085887, 2087465

Email :

hernandez.bernal@cigb.edu.cu [2]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000189

Date of Registration in Primary Registry:

10/11/2014

Record Verification Date:

2014/11/10

Next update date:

2015/11/10

Link to the spanish version:

Click here [3]