A clinical study of OPT-302 with ranibizumab compared to ranibizumab alone in patients with neovascular age-related macular degeneration

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2017-002698-20-ES
• Date of registration: 15/02/2018
• Prospective Registration: Yes
• Primary sponsor: Opthea Ltd
• Public title: A clinical study of OPT-302 with ranibizumab compared to ranibizumab alone in patients with neovascular age-related macular degeneration
• Scientific title: A dose-ranging study of intravitreal OPT-302 in combination with ranibizumab, compared with ranibizumab alone, in participants with neovascular age-related macular degeneration (wet AMD)
• Date of first enrolment: 16/02/2018
• Target sample size: 351
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002698-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Sham injection; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Hungary, Israel, Italy, Latvia, Poland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Development
• Affiliation: Opthea Ltd

• Name: Clinical Development
• Affiliation: Opthea Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
STUDY EYE
1. Active subfoveal choroidal neovascular (CNV) lesion or juxtafoveal CNV lesion (1-199 µm from the fovea) with subfoveal involvement (demonstrated by leakage on fluorescein angiography (FA) and/or intra-retinal or sub-retinal fluid on spectral-domain optical coherence tomography [SD-OCT]) secondary to age-related macular degeneration (AMD). Active CNV as measured on FA must constitute at least 50% of the lesion area, with a total lesion size of = 30.5 mm2. The lesion may contain classic and/or occult CNV, but any occult CNV present must measure < 10 mm2 on the FA. The characteristics of each lesion must be confirmed by the Independent Reading Centre.
2. A best corrected (ETDRS) visual acuity (BCVA) score between 60 and 25 (inclusive) letters (Snellen equivalent of 20/63 (feet) or 6/21 (metres) and 20/320 (feet) or 6/96 (metres) respectively).

GENERAL
1. Willing and able to provide written informed consent.
2. Male or female participants at least 50 years of age.
3. Able to understand and willing to comply with study protocol procedures and restrictions.
4. If female and of child-bearing potential: Pregnancy test at Screening is negative, and agrees to use an highly effective method of contraceptive for the duration of the study and for at least 3 months following the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 326

Exclusion criteria:
STUDY EYE
1. Any previous treatment for wet AMD, including anti-VEGF-A therapy, photodynamic therapy, thermal laser, external beam radiation, steroids or other AMD therapy in the Study Eye. Oral supplements of vitamins and minerals are permitted.
2. Clinically significant ocular disorders (other than wet AMD), which may, in the Investigator’s opinion, interfere with assessment of visual acuity, assessment of safety, OCT, fluorescein angiography or fundus photography;
3. Haemorrhage measuring more than 50% of total lesion area;
4. Fibrosis involving either the fovea centre or measuring more than 25% of the total lesion area and/or juxtafoveal or sub-foveal geographic atropy
5. Choroidal neovascularisation due to causes other than AMD, including presumed ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, and pathological myopia. Participants with retinal angiomatous proliferation (RAP) or idiopathic polypoidal choroidal vasculopathy (IPCV) are not excluded.
6. Cloudy ocular media, or inadequate pupillary dilatation, so as to prevent collection of fundus photographs and/or fluorescein angiograms of sufficient quality to be analysed by the Independent Reading Centre.
7. Presence of intraocular inflammation (= trace cell or flare), significant epiretinal membrane or vitreomacular traction, macular hole or vitreous haemorrhage.
8. Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is permitted if it occurred as a result of a YAG laser posterior capsulotomy in association with prior posterior chamber intraocular lens implant.
9. History of idiopathic or autoimmune-associated uveitis.
10. Any current ocular or periocular infection (participants may be re-screened once the infection has resolved or responded fully to treatment).
11. Intraocular pressure of greater than 25 mmHg (including participants with glaucoma or ocular hypertension who are stabilised on therapy).
12. Myopia, or known former myopia, with a spherical equivalent of greater than 8 dioptres.
13. Intraocular surgery within 6 months prior to screening, except for cataract surgery that is excluded within 3 months of Screening.
14. History of any of the following conditions or procedures: Rhegmatogenous retinal detachment, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, or corneal transplant.
15. Prior pars plana vitrectomy.
16. Presence of an intravitreal device.
17. Retinopathy from diabetes, sickle cell disease or other cause.

NON-STUDY EYE
1. History of idiopathic, autoimmune-associated, or infectious uveitis.

GENERAL
1. Poorly controlled diabetes mellitus (defined as HbA1c > 7.0%).
2. Administration of systemic steroids within 3 months of screening.
3. Symptoms of heart failure leading to marked limitation on physical activity, or inability to perform any physical activity without discomfort.
4. Unstable angina, myocardial infarction or coronary artery revascularisation within 6 months of screening.
5. Ventricular tachyarrhythmia requiring ongoing treatment.
6

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neovascular age-related macular degeneration (wet AMD)
MedDRA version: 20.0 Level: SOC Classification code 10015919 Term: Eye disorders System Organ Class: 10015919 - Eye disorders
MedDRA version: 20.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders
MedDRA version: 20.1 Level: LLT Classification code 10067791 Term: Wet macular degeneration System Organ Class: 10015919 - Eye disorders

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Product Name: OPT-302
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vascular endothelial growth factor receptor-3 (VEGFR-3) derivative fused to a human immunoglobulin (IgG)1 Fc fragment (no proposed INN at this stage)
Current Sponsor code: OPT-302
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Lucentis 10 mg/ml solution for injection in pre-filled syringe
Product Code: S01LA04
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: RANIBIZUMAB
CAS Number: 347396-82-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24 (Visit 8)

Secondary Objective: *Determine the proportion of participants gaining 15 or more ETDRS BCVA letters from Baseline to Week 24;
*Determine the area under the ETDRS BCVA over time curve;
*Determine the change in central subfield thickness (CST) on spectral domain optical coherence tomography (SD-OCT) from Baseline to Week 24;
*Determine the change in sub-retinal fluid on SD-OCT from Baseline to Week 24;
*Determine the presence or absence of intra-retinal fluid on SD-OCT from Baseline to Week 24;
*Determine the proportion of participants losing 15 or more letters (on ETDRS BCVA chart) from Baseline to the Week 24 Visit;
*Determine the safety of OPT-302 in combination with ranibizumab;
*Determine the pharmacokinetic parameters of OPT-302;
*Determine the incidence of anti-OPT 302 antibody (ADA) formation.

Primary end point(s): Mean change from Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) letters to Week 24 (Visit 8)

Main Objective: Determine the efficacy of two different doses of intravitreal OPT-302 when administered in combination with ranibizumab in participants with wet AMD

Secondary Outcome(s)

Secondary end point(s): * The proportion of participants gaining 15 or more ETDRS BCVA letters from Baseline to the Week 24 Visit;
* Area under the ETDRS BCVA-over-time curve;
* Change in (CST) on SD-OCT from Baseline to Week 24;
* Change in sub-retinal fluid on SD-OCT from Baseline to Week 24;
*Presence or absence of intra-retinal fluid determined by the presence or absence of intra retinal cysts on SD-OCT from baseline to week 24;
* Proportion of participants losing 15 or more letters (on ETDRS BCVA chart) from Baseline to the Week 24 Visit;
*Incidence of ocular and non-ocular adverse events (AEs);
*OPT-302 pharmacokinetic parameters;
*Particpant incidence of ADA formation.

Timepoint(s) of evaluation of this end point: Week 24 (Visit 8)

Secondary ID(s)

OPT-302-1002

2017-002698-20-CZ

NCT03345082

Source(s) of Monetary Support

Opthea Ltd

Ethics review

Status: Approved
Approval date:
Contact: