A Phase 3 Study to Compare Efficacy, Safety, Pharmacokinetics, and Immunogenicity of Test Product (BP05) Versus Reference Product (Lucentis®) in Patients with Wet (Neovascular) Age-Related Macular Degeneration.
Scientific Title of Study
A Phase 3, Randomized, Double-Blind, Parallel Group, Multicenter Study to Compare Efficacy, Safety, Pharmacokinetics, and Immunogenicity of BP05 Versus EU-Approved Lucentis® in Patients with Wet (Neovascular)
Age-Related Macular Degeneration.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CR213-20,Original, Version 1.0, dated 01/ February/ 2021
Protocol Number
CT/21/000032
DCGI
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Subhra Lahiri
Designation
Sr Vice President
Affiliation
AXIS Clinicals Ltd
Address
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA Hyderabad TELANGANA 500049 India
Phone
8886221089
Fax
914040408060
Email
Subhra.L@axisclinicals.com
Details of Contact Person Scientific Query
Name
Dr Subhra Lahiri
Designation
Sr Vice President
Affiliation
AXIS Clinicals Ltd
Address
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA
TELANGANA 500049 India
Phone
8886221089
Fax
914040408060
Email
Subhra.L@axisclinicals.com
Details of Contact Person Public Query
Name
Dr Subhra Lahiri
Designation
Sr Vice President
Affiliation
AXIS Clinicals Ltd
Address
AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA AXIS Clinicals Ltd
1-121/1 Miyapur Hyderabad 500049
Telangana INDIA
TELANGANA 500049 India
Phone
8886221089
Fax
914040408060
Email
Subhra.L@axisclinicals.com
Source of Monetary or Material Support
CuraTeQ Biologics Private Ltd
Primary Sponsor
Name
CuraTeQ Biologics Private Ltd
Address
Plot No.2, Maitrivihar, Ameerpet,
Hyderabad, Telangana, India, 500038
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AXIS Clinicals Ltd
1-121/1 Miyapur, Hyderabad-500049
Andhra Pradesh, INDIA
Countries of Recruitment
Bosnia and Herzegovina Bulgaria Hungary India Macedonia Russian Federation Serbia
Swami Vivekanand Netra Mandir Super Specialty Eye Centre
Swami Vivekanand Netra Mandir Super Specialty Eye Centre
4Th Floor 300-303, Shlok Business Centre, Beside Apple Hospital
Udhna Darwaja, Ring Road, Surat ,395002,Gujarat Surat GUJARAT
INSTITUTIONAL ETHICS COMMITTEE-GMERS medical college
Approved
Institutional Human Ethics Committee - PSG Institute of Medical Science and Research
Approved
Magna care Ethics Committee
Approved
NARAYANA NETHRALAYA ETHICS COMMITTEE
Approved
Netrajyothi Institute of Ethics Committee
Approved
Ojas Multispecialty Hospital Ethics Committee
Approved
Opal Institutional Ethics Committee
Approved
Sangini Hospital Ethics Committee
Approved
Somani Hospital Ethics Commitee
Approved
Triveni Polyclinic Institutional Ethics committee
Approved
Tulsi Hospital Ethics Committee
Approved
Virtuous Institutional Medical Research EC
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: H353||Degeneration of macula and posterior pole,
Intervention / Comparator Agent
Type
Name
Details
Intervention
BP05
Single IVT injection containing 0.5 mg dose of BP05 as per randomization every 4 weeks for 13 cycles.
Comparator Agent
Lucentis®
Single IVT injection containing 0.5 mg dose of Lucentis as per randomization every 4 weeks for 13 cycles.
Inclusion Criteria
Age From
50.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1.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.
2.Willing and able to undertake all scheduled visits and assessments as judged by the investigator.
3.Age ≥50 years at Screening.
4.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.
5.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.
6.Total lesion area ≤12.0 disc areas in size (including blood, scars, and neovascularization) as assessed by FA in the study eye and confirmed by the central reading center prior to randomization.
7.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.
ExclusionCriteria
Details
1.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.
2.Scarring in the study eye exceeding 50% of total lesion size.
3.Subfoveal fibrosis or atrophy in the study eye assessed by FA and confirmed by central reading center.
4.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.
5.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.
6.History or presence of macular hole in the study eye at Screening, confirmed by central reading center.
7.History or clinical evidence of diabetic retinopathy (except for mild non-proliferative diabetic retinopathy) or diabetic macular edema in either eye.
8.History of vitrectomy surgery in the study eye.
9.History of trabeculectomy or other filtration surgery in the study eye.
10.History of submacular surgery or other surgical intervention for AMD in the study eye.
11.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
12.Any previous IVT anti-VEGF treatment (eg, bevacizumab, aflibercept, ranibizumab) in either eye.
13.Any previous systemic anti-VEGF treatment, within 90 days prior to randomization, and such treatment will not be allowed during the study period.
14.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.
15.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.
16.Topical ocular corticosteroids administered for ≥30 consecutive days in the study eye within 90 days prior to Screening.
17.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.
18.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.
19.Presence of scleromalacia in either eye.
20.Current vitreous hemorrhage in the study eye.
21.Active or recent (within 28 days prior to randomization) intraocular, extraocular, and periocular inflammation or infection in either eye.
22.History of idiopathic or autoimmune-associated uveitis in either eye.
23.Corneal transplant in the study eye.
24.Presence of advanced glaucoma or optic neuropathy that involve or threaten the central visual field in the study eye.
25.Uncontrolled ocular hypertension in the study eye, defined as IOP ≥30 mmHg despite treatment with antiglaucoma medication
26.History of allergy to the fluorescein sodium for injection in angiography.
27.Contraindication for any of the excipients in BP05 or Lucentis (active or suspected ocular or periocular infection, or active severe intraocular inflammation).
28.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).
29.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.
30.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.
31.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.
32.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.
33.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.
34.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.
35.Stroke, transient ischemic attacks, or myocardial infarction within 90 days prior to randomization
36.History of recurrent significant infections and/or current treatment for active systemic infection.
37.Pharmacokinetic subgroup only: contraindication for additional blood sampling (as judged by the investigator).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of a biosimilar candidate BP05 versus Lucentis in patients with wAMD
Week 48 and Week 52
Secondary Outcome
Outcome
TimePoints
To evaluate the efficacy of BP05 versus Lucentis in patients with wAMD based on CFT, area of CNV, and leakage from CNV lesion
Change in BCVA letters over the course of the study compared with baseline in the study eye using the ETDRS chart
Change in total size of CNV leakage area at Week 24 Week 52 compared with baseline in the study eye, as measured by FA
Change in total size of CNV at Week 24 Week 52 compared with baseline in the study eye, as measured by FA
Change in CFT at Week 4 Week 8 Week 16 Week 24 Week 52 compared with baseline in the study eye as measured by spectral domain OCT
To evaluate the systemic exposure of BP05 versus Lucentis in patients participating in PK evaluation
Number of patients without intra/subretinal fluid at Week 24 and Week 52 in the study eye
Drug concentrations (Cmax) analyzed after the collection of blood at the following time points:
Before administration of the study drug at Cycle 1
22 hours ± 1 hour after the administration of the first and the sixth dose
Target Sample Size
Total Sample Size="550" Sample Size from India="275" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 3, multicenter, randomized, double-blind, multi-dose, parallel group, activecomparator study comparing the efficacy, safety, PK, and immunogenicity profiles of BP05withthecomparatormarketedproduct,Lucentis,inpatientswithwAMD.Effortswillbemadeto include approximately 30% of the patients with light iris color to meet the FDA and EUregulations Atotalof550patientswithwAMDwillberandomizedinthisstudyinapproximately65sitesacrosstheglobe.Efforts willbemadetorecruitapproximately50%ofthepatientsfromIndiaand 50% of the patients from Europe and Russia. Each patient will be assigned a screeningnumberandevaluatedfortheinclusionandexclusioncriteriaaspartofthescreeningprocedures. Patients who meet all of the inclusion criteria and none of the exclusion criteriawill be randomly assigned and treated on Day 1. At this visit, the patient will be randomlyassignedin 1:1 ratio using IWRS to oneofthe following cohorts :Cohort1:BP05(275patients withwAMD) Cohort2:Lucentis(275patients withwAMD) Thestudyisdesignedtocompare2preparationsofranibizumab(BP05orLucentis)inpatientswith wAMD when administered as a single IVT injection of 0.05 mL (0.5 mg) into the studyeye on Day 1 of 4-week cycle. Randomization will be stratified by baseline BCVA scores,baselineCNVclassification,andcountry.PatientswillbetreatedwitheitherBP05orLucentisevery4weeksuntilWeek48asdetailedintheScheduleofEvents. Pharmacokinetic evaluation will be performed in a subset of patients whoprovided consent (20 patients in each treatment group). This study includes a screening duration up to 2 weeks, study treatment duration up to 48weeks,andthefollow-updurationupto4weeks;thus,thetotaldurationofstudyparticipationisapproximately up to 54 weeks.All patients will be assessed once every 4 weeks as detailed in the Schedule of Events. TheEOTvisitwillbescheduledatWeek48forthosewhoreceiveallthescheduledinjections.TheEOSvisitwilloccuratWeek52,whichis4weeksafterthe EOTvisitforpatientswhoreceiveallthescheduledinjections.Theendofthestudyisdefinedasthe date ofthelast visitof thelastpatient in thestudy.