Phase 3 Randomized Study Comparing Efficacy and Safety of BP05 and Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration
- Trial ID
- 2023-507459-31-03
- Protocol
- CR213-20
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, randomized, double-blind, parallel group, multicenter study is to evaluate the **efficacy** of the biosimilar candidate BP05 compared to Lucentis in patients with wet age-related macular degeneration (wAMD). This is clinically relevant as it aims to determine if BP05 can provide a comparable therapeutic benefit to Lucentis, a well-established treatment for wAMD, potentially offering an alternative treatment option.
Secondary objectives include:
- Evaluating the efficacy of BP05 versus Lucentis based on central foveal thickness (CFT), area of choroidal neovascularization (CNV), and leakage from the CNV lesion.
- Assessing the safety profile of BP05 in comparison to Lucentis.
- Determining the immunogenicity of BP05 relative to Lucentis.
- Evaluating the systemic exposure of BP05 versus Lucentis in patients participating in pharmacokinetic (PK) evaluation.
Participants
The clinical trial involves a total of **480 participants** diagnosed with **wet macula degeneration**. The study population includes both male and female subjects, aged **50 years and older**, who are in general good health and capable of understanding and providing informed consent. Participants were selected based on their diagnosis of active subfoveal choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) in the study eye, with specific criteria regarding the lesion area and visual acuity. The trial does not include a vulnerable population, and participants are expected to comply with scheduled visits and assessments. Lifestyle considerations such as diet and physical activity are not specified, but participants of childbearing potential are required to use effective contraception. The selection process ensures that the trial population is representative of the target demographic for evaluating the efficacy of the biosimilar candidate BP05 versus Lucentis in patients with wet AMD.
Plans and Procedures
The clinical trial is a **Phase 3**, randomized, double-blind, parallel-group, multicenter study designed to compare the efficacy, safety, pharmacokinetics, and immunogenicity of BP05 versus EU-approved Lucentis in patients with **wet age-related macular degeneration** (wAMD). The trial will involve a total treatment period of 48 weeks, with an estimated recruitment start date of June 28, 2024, and an estimated end date of December 31, 2025. Participants will be randomly assigned to receive either BP05 or Lucentis, both administered as an **injection** for **intravitreal use**. The primary endpoint is the change in best-corrected visual acuity (BCVA) letters at Week 8 compared with baseline, using the ETDRS chart. Secondary endpoints include changes in BCVA over the course of the study, changes in the size of choroidal neovascularization (CNV) leakage area, and other ocular and systemic safety parameters.
The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits at specified intervals throughout the study duration. The inclusion visit will assess the patient's ability to understand and provide informed consent, willingness to comply with protocol requirements, and specific ophthalmic criteria such as the presence of active subfoveal CNV lesions. Follow-up visits will occur at Weeks 4, 8, 16, 24, and 52, with assessments including BCVA, CNV size, and intra/subretinal fluid status. The end-of-study visit will evaluate the overall treatment outcomes and any adverse events experienced by the participants.
Participant involvement is expected to last approximately 52 weeks, including the screening period. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events that compromise participant safety. The trial is not classified as low intervention, and the study design ensures rigorous monitoring and data collection to achieve the trial's objectives.
Treatment
The clinical trial involves the administration of two **experimental medications** to evaluate their efficacy, safety, pharmacokinetics, and immunogenicity in patients with wet (neovascular) age-related macular degeneration (wAMD). The first medication is **Lucentis 10 mg/ml solution for injection**, which contains the active substance **ranibizumab**. This medication is provided in the form of a solution for injection and is administered via **intraocular use**. The dosage is set at a maximum daily dose of 0.5 mg, with a total maximum dose of 6.5 mg over a treatment period of 48 weeks. The pharmaceutical product is manufactured by Novartis Europharm Limited and is authorized under the marketing authorization number EU/1/06/374/004.
The second medication used in the trial is a biosimilar candidate known as **Ranibizumab**, produced by Curateq Biologics Private Ltd. This product is also administered as an **injection** via **intravitreal use**. The dosage for this medication is similarly capped at a maximum daily dose of 0.5 mg, with a total maximum dose of 6 mg over the same 48-week treatment period. The sponsor product code for this biosimilar is BP05, and it is identified with the marketing authorization number V11/2021. Both medications are derived from a protein origin classified as "Protein - Other" and are not pediatric formulations.
Throughout the trial, participant compliance with the dosing schedule will be closely monitored to ensure adherence to the prescribed treatment regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the study protocol. The trial is designed as a Phase 3, randomized, double-blind, parallel-group, multicenter study to provide robust data on the comparative performance of the biosimilar candidate against the EU-approved Lucentis.
Efficacy
The efficacy of the biosimilar candidate BP05 versus Lucentis in patients with wet (neovascular) age-related macular degeneration (wAMD) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change in Best Corrected Visual Acuity (BCVA) letters at Week 8 compared with baseline in the study eye, using the ETDRS chart. Secondary endpoints include the change in BCVA letters over the course of the study, the change in the total size of choroidal neovascularization (CNV) leakage area at Week 24 and Week 52, and the change in central foveal thickness (CFT) at multiple time points, including Week 4, Week 8, Week 16, Week 24, and Week 52, as measured by spectral domain optical coherence tomography (OCT).
Additional secondary endpoints involve the percentage of patients with a loss of ≤15 letters and those with a gain of >15 letters using the ETDRS chart, evaluated at Week 8, Week 24, and Week 52. The change in intra/subretinal fluid status and the number of patients without intra/subretinal fluid at Week 24 and Week 52 will also be assessed using OCT. Pharmacokinetic parameters such as drug concentrations (Cmax) will be analyzed after blood collection at specified time points, including before administration at Cycle 1 and 22 hours ± 1 hour after the administration of the first and sixth doses. Immunogenicity will be evaluated by measuring the incidence of anti-drug antibodies (ADAs) to **ranibizumab** at various time points, including pre-dose on Day 1, Week 4, Week 12, Week 20, Week 36, and Week 52, with the incidence of neutralizing antibodies (NAbs) assessed in all ADA-positive patients.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient or patient’s legally authorized representative is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
- Willing and able to undertake all scheduled visits and assessments as judged by the investigator.
- Age ≥50 years at Screening
- Patients diagnosed with active* subfoveal CNV lesion secondary to AMD in the study eye. *Active CNV means presence of leakage as evidenced by FA and intra/subretinal fluid as evidenced by OCT, which should be confirmed by the central reading center at Screening
- The area of CNV must be ≥50% of the total lesion area in the study eye and confirmed by the central reading center prior to randomization
- Total lesion area ≤12.0 disc areas in size (including blood, scars, and neovascularizati-on) as assessed by FA in the study eye and confirmed by the central reading center prior to randomization
- Best corrected visual acuity of 20/40 to 20/200 in the study eye using ETDRS chart at Screening
- Nonchildbearing potential female (eg, permanently sterilized, postmenopausal [defined as 12 months with no menses without an alternative medical cause prior to Screening]), OR Childbearing potential female patients or male patients with their (respectively male or female) partners who agree to use at least 2 forms of appropriate contraception method that can achieve a failure rate of less than 1% per year from Screening until 3 months after the last IVT injection of the study drug.
Exclusion Criteria
- Sub- or intraretinal hemorrhage involving the fovea in the study eye of 50% or more of the total lesion area assessed by FA and confirmed by central reading center.
- Scarring in the study eye exceeding 50% of total lesion size.
- Subfoveal fibrosis or atrophy in the study eye assessed by FA and confirmed by central reading center.
- Presence of CNV in either eye due to non-AMD causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture or pathologic myopia, assessed by FA and confirmed by central reading center.
- History or presence of RPE tear or retinal detachment involving the macula in the study eye and fellow eye as assessed by FA and confirmed by central reading center.
- History or presence of macular hole in the study eye at Screening, confirmed by central reading center.
- History or clinical evidence of diabetic retinopathy (except for mild non-proliferative diabetic retinopathy) or diabetic macular edema in either eye
- History of vitrectomy surgery in the study eye.
- History of trabeculectomy or other filtration surgery in the study eye
- History of submacular surgery or other surgical intervention for AMD in the study eye
- Any other intraocular surgery (including cataract surgery) or periocular surgery in the study eye within 90 days prior to randomization, except for lid surgery, which may not have taken place within 30 days prior to randomization
- Any previous IVT anti-VEGF treatment (eg, bevacizumab, aflibercept, ranibizumab) in either eye
- Any previous systemic anti-VEGF treatment, within 90 days prior to randomization, and such treatment will not be allowed during the study period.
- Any systemic treatment or therapy (including prescribed herbal medication) to treat wAMD within 30 days prior to randomization, and such treatment or therapy will not be allowed during the study period. However, dietary supplements, vitamins, or minerals will be allowed.
- Any IVT injection of corticosteroid (eg, triamcinolone acetonide) or IVT corticosteroid implant in the study eye within 180 days prior to randomization, and such treatment will not be allowed during the study period
- Topical ocular corticosteroids administered for ≥30 consecutive days in the study eye within 90 days prior to Screening
- Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia. For patients who have undergone previous refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye must not exceed 8 diopters of myopia
- Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a yttrium aluminium garnet posterior capsulotomy in association with prior posterior chamber intraocular lens implantation
- Presence of scleromalacia in either eye
- Current vitreous hemorrhage in the study eye
- Active or recent (within 28 days prior to randomization) intraocular, extraocular, and periocular inflammation or infection in either eye
- History of idiopathic or autoimmune-associated uveitis in either eye
- Corneal transplant in the study eye
- Presence of advanced glaucoma or optic neuropathy that involve or threaten the central visual field in the study eye
- Uncontrolled ocular hypertension in the study eye, defined as IOP ≥30 mmHg despite treatment with antiglaucoma medication
- History of allergy to the fluorescein sodium for injection in angiography
- Contraindication for any of the excipients in BP05 or Lucentis (active or suspected ocular or periocular infection, or active severe intraocular inflammation)
- Reasonable suspicion of a disease or condition that might render the patient at high risk of treatment complications or affect interpretation of the study results (as judged by the investigator)
- Previous participation in clinical studies of ocular investigational products to treat wAMD in either eye or systemic investigational products to treat wAMD, and such participation will not be allowed during the study period
- Previous participation in any studies of ocular or systemic investigational products (excluding dietary supplements, vitamins, and minerals) to treat ocular or systemic disease other than wAMD within 90 days prior to randomization, and such participation will not be allowed during the study period even if the investigational product is dietary supplements, vitamins, or minerals
- Any concurrent ocular condition in the study eye, which in the opinion of the investigator, could either increase the risk to the patient safety or which otherwise may interfere with evaluation of efficacy or safety including, but not limited to ocular media opacities such as corneal opacity or cataract that do not allow proper fundus visualization and fundus imaging, and ocular surface abnormalities, which prevent applanation tonometry during the study period after randomization
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the study drug in the opinion of the investigator
- Pregnant or lactating women. A urine pregnancy test must be required for women of childbearing potential at Screening and must agree to pregnancy prevention throughout the duration of the study.
- Employees of investigational sites, individuals directly involved with the conduct of the study or immediate family members thereof, prisoners, and persons who are legally institutionalized
- Stroke, transient ischemic attacks, or myocardial infarction within 90 days prior to randomization
- History of recurrent significant infections and/or current treatment for active systemic infection.
- Pharmacokinetic subgroup only: contraindication for additional blood sampling (as judged by the investigator).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Latvia | Not Recruiting | 28 Jun 2024 | 30 |
 Slovakia | Not Recruiting | 28 Jun 2024 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Lucentis 10 mg/ml solution for injection | Comparator | SOLUTION FOR INJECTION | INTRAOCULAR USE | 0.5 | 48 | PRD3945696 |
Ranibizumab | Test | INJECTION | INTRAVITREAL USE | 0.5 | 48 | PRD10070170 |