Xplore: A Phase III Double-Blind, Parallel Group, Multicenter Study to Compare the Efficacy and Safety of Xlucane versus Lucentis® in Patients with Neovascular Age-Related Macular Degeneration
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 580
- 试验地点
- 40
- 主要终点
- Change in Best Corrected Visual Acuity (BCVA) [ Time Frame: Week 8 ]
研究概览
简要总结
This is a phase IIImulticenter, double-blind (double-masked), randomized, parallel group study insubjects with wAMD. Approximately 580 subjects will be enrolled and randomizedin a 1:1 ratio to receive either Lucentis® (0.05 mL of 10 mg/mL ranibizumab) orthe investigational product (IP), Xlucane (0.05 mL of 10 mg/mL ranibizumab), inthe study eye once every 4 weeks for 52 weeks (ie, 12 months).
The study eye will be definedas the eye meeting all of the inclusion criteria and none of the exclusioncriteria (ie, the enrollment criteria).
The assigned study drug will beadministered as an ophthalmic intravitreal (IVT) injection. Designated,unmasked study staff will prepare and administer the study drug, ensuring thatthe masking of the subject is maintained during the injection procedure. See Section 8.4.6.
Subjects will be randomized byinteractive web response system (IWRS) to receive 13 doses of either Xlucane orLucentis® in the study eye. The randomization scheme will automatically ensurethat the study drug assignment for a given subject is random and that anoverall 1:1 ratio of assignments to each of the 2 study drug treatments isapproximated. In addition, the randomization scheme will include the followingstratification parameters to ensure balanced distribution of assignment to the2 treatments: eye color (light iris vs dark iris), geographical region whereenrolled and the BCVA letters at Baseline. Subjects will be followed up forchanges in efficacy variables and safety for 52 weeks. Each subject’sinvolvement will last up to approximately 52 weeks (ie, 12 months).
At the beginning of the study,a subgroup of 60 subjects at a select number of participating sites will besequentially asked to participate in an evaluation of PK. This subgroup will beasked to provide blood samples for measurement of serum ranibizumab immediatelybefore administration of the first dose of Xlucane or Lucentis®. Additionalsamples will be collected 23 hours after the first dose (ie, Day 1) and 23hours after the sixth dose (ie, Week 20) at expected time to maximum serumconcentration (Tmax, which is around 22 hours). The primary analysis set willbe the Per-Protocol population.
An interim analysis will beperformed on unmasked study data. After all of the randomized subjectshave 6-month (ie, 24 weeks) data available, an unmasked analysis ofefficacy and safety endpoints as well as PK and immunogenicity will beperformed. The aim of this analysis is to obtain results prior to completion offull follow-up for all subjects. This analysis will not affect the furtherconduct of the study.
FA, CFP,and OCT will performed at Screening. The images will be sent to the centralreading center (CRC) for interpretation and confirmation of eligibility. TheCRC will also grade images that are collected during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 50.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Written and signed informed consent form obtained at screening, before any study-related procedures.
- •Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator.
- •Newly diagnosed, active subfoveal Choroidal Neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD) in the study eye.
- •Note: Active CNV indicates the presence of leakage as evidenced by Fluorescein Angiography (FA) and intra- or subretinal fluid as evidenced by Optical Coherence Tomography (OCT) which must be confirmed by the central reading center during Screening: a) The area of CNV must be greater than equal to 50% of the total lesion area in the study eye, and b) Total lesion area Less than equal to 9.0 Disc Areas (DA) in size (including blood, scars and neovascularization) as assessed by FA in the study eye.
- •Best Corrected Visual Acuity (BCVA) of less than equal to 73 and greater than equal to 49 ETDRS letter score in the study eye, using ETDRS chart (20/40 to 20/100 Snellen equivalent) at Screening.
- •Fellow eye should not be expected to need any anti-VEGF treatment for the duration of study participation.
- •Age greater than equal to 50 years at screening.
- •Male and female subjects of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug.
排除标准
- •Any previous intervention including pharmacological treatment, laser and/or surgery for wAMD in either eye; (Exception: Vitamin supplementation for AMD prevention).
- •Any previous vitreoretinal surgery in the study eye for any cause.
- •Any previous IVT treatment including any anti-VEGF medications, steroids and/or any other investigational medication in either eye.
- •The use of long-acting steroids, either systemic or intraocular in any eye, in the 18 months before planned initiation of study treatment.
- •(Note: Iluvien® [fluocinolone acetonide intravitreal], current or planned implantation during the study, is prohibited.) 4) Subfoveal fibrosis, atrophy or scarring extending greater than 50% of total lesion area, in the study eye as assessed by the investigator at screening and confirmed by the central reading center prior to randomization.
- •Choroidal neovascularization in either eye due to non-AMD causes (eg, DME, RVO, ocular histoplasmosis or trauma, etc.) as assessed by FA and confirmed by central reading center.
- •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.
- •Infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
- •Unmedicated intraocular pressure (IOP) more then equal to 30 mmHg at Screening in either eye.
- •Topical ocular corticosteroids administered for greater than equal to 30 consecutive days in the study eye within 90 days prior to Screening.
- •Spherical equivalent of the refractive error in the study eye demonstrating greater than 8 diopters of myopia.
- •Corneal transplant or corneal dystrophy in the study eye.
- •History of rhegmatogenous retinal detachment in the study eye.
- •History of macular hole in the study eye.
- •Retinal pigment epithelial tear or rip, involving the macula in the study eye as assessed by FA and confirmed by the central reading center.
- •Current vitreous hemorrhage in the study eye.
- •Subretinal hemorrhage that is greater than equal to 50% of the total lesion area in the study eye, or if the subretinal hemorrhage involves the fovea is 1 or more DA (greater than equal to 2.54 mm2) in size in the study eye, as assessed by FA and confirmed by the central reading center.
- •Other intraocular surgery (including cataract surgery) in the study eye within the 3 months prior to baseline.
- •The yttrium aluminum garnet [YAG] posterior capsulotomy is allowed not later than 4 weeks prior to screening.
- •Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could require treatment during the study period to prevent or treat loss of visual acuity.
- •Significant media opacities (including cataract) in the study eye interfering with BCVA assessment or fundus imaging (FA/FP/OCT).
- •Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation.
- •Presence of advanced glaucoma or optic neuropathy that involve(s) or threaten(s) the central visual field in the study eye (as judged by the investigator).
- •History of glaucoma filtering surgery or argon laser trabeculoplasty in the study eye (Exception: Laser iridotomy and selective laser trabeculoplasty are allowed).
- •Uncontrolled ocular glaucoma or hypertension in the study eye, defined as IOP greater than equal to 25 mmHg despite treatment with anti-glaucoma medication.
- •Any previous systemic anti-VEGF treatment (eg, bevacizumab).
- •Current treatment for active systemic infection.
- •Females who are pregnant, nursing, planning a pregnancy during the study, or of childbearing potential and not using a reliable method of contraception and/or not willing to use a reliable method of contraception during their participation in the study.
- •Participation in another clinical trial within the previous 3 months or any other clinical trial of anti-angiogenic drugs.
- •Reasonable suspicion of other disease or condition that might render the subject at a high risk of treatment complications or otherwise confound interpretation of the study results (as judged by the investigator).
- •PK subgroup only: Contraindication for additional blood sampling (as judged by the investigator).
结局指标
主要结局
Change in Best Corrected Visual Acuity (BCVA) [ Time Frame: Week 8 ]
时间窗: Time Frame: Week 8
Change(s) in BCVA letters at Week 8 compared to baseline using the ETDRS protocol
时间窗: Time Frame: Week 8
次要结局
- Change in BCVA using the ETDRS protocol(Total size of choroidal neovascular leakage area measured by FA)