Clinical trial NCT05727397: Efficacy and Safety of RC28-E Versus Aflibercept
Official title: A Randomized, Double-Masked, Multicenter, Two-Arm Study Comparing the Efficacy and Safety of RC28-E 2mg Versus Aflibercept in Subjects With Wet Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Wet Age-related Macular Degeneration
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 432
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-masked, multicenter study comparing the the efficacy and safety of RC28-E injection (a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF-2) versus aflibercept in patients with wet age-related macular degeneration.


Eligibility criteria: Inclusion Criteria:

* Sign the consent form, willing and able to comply with clinic visits and study-related procedures;
* 50 years of age or older;
* Diagnosed with wAMD;
* Active CNV lesion of any type (ie, predominantly classic, minimally classic, or occult \[including polypoidal choroidal vasculopathy and retinal angiomatous proliferation\]) that exhibits all of the following characteristics:

  * The CNV or sequela of the CNV affect the foveal;
  * A total lesion size of ≤12 disc areas on FFA;
  * Evidence of CNV leakage on FFA;
  * Intra and/or subretinal fluid confirmed on OCT;
* BCVA of 78-19 letters using the ETDRS protocol;
* Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good-quality retinal images to confirm diagnosis.

Exclusion Criteria:

For the study eye:

* CNV due to causes other than AMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis;
* Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid;
* Presence at screening of central serous chorioretinopathy;
* Retinal pigment epithelial tear involving the foveola on day 1;
* Fibrosis or atrophy involves the foveola;
* Subretinal haemorrhage involves the foveola;
* Any concurrent intraocular condition (eg, amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, or epiretinal membrane with traction) that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study;
* Current vitreous hemonhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to baseline;
* Uncontrolled glaucoma;
* Spherical equivalent of refractive error demonstrating ≥8 diopters of myopia;
* Previous treatment with anti-VEGF therapy within the 3 months period prior to baseline;
* Intraocular use of long-acting corticosteroids during the 6 month period prior to baseline; intraocular use of short or medium-acting corticosteroids during the 3 month period prior to baseline; periocular use of corticosteroids during the 1 month period prior to baseline;
* Use of topical ocular corticosteroids for 60 or more consecutive days within the 3 month period prior to baseline;
* Macular laser treatment, PDT, TTT or other surgical intervention for AMD within the 3 month period prior to baseline;
* Any cataract surgery or treatment for complications of cataract surgery with steroids within the 3 month period prior to baseline; YAG laser capsulotomy within 1 month before baseline;
* Aphakia or pseudophakia with absence of posterior capsule, unless it occurred as a result of YAG posterior capsulotomy;
* Intraocular or refractive surgery within the 3 month period prior to baseline;
* Previous penetrating keratoplasty or vitrectomy or panretinal photocoagulation or radiotherapy;

For the fellow eye or both eyes:

* Non-functioning non-study eye;
* Treatment with anti-VEGF therapy within the 7 day period prior to baseline in the nonstudy eye;
* Any history of idiopathic or autoimmune-associated uveitis in either eye;
* Current active ocular inflammation or suspected or active ocular or periocular infection in either eye;

General exclusion criteria:

* Any major illness or major surgical procedure within 1 month before screening;
* Active cancer within the past 12 months except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of \<6 and a stable prostate-specific antigen for \>12 months;
* Requirement for continuous use of any medications and treatments indicated as prohibited therapy;
* Systemic anti-VEGF therapy within the 3 month period prior to baseline;
* Use of systemic corticosteroids for 30 or more consecutive days within the 3 months prior to baseline, with the exception of low stable doses of corticosteroids (defined as ≤10 mg/day prednisolone or equivalent dose)；
* Systemic treatment for suspected or active systemic infection on baseline;
* COVID-19 infection within the 4 week period prior to screening; Hospitalization required severe COVID-19 infection within the 12 month period prior to screening;
* HBsAg(+) and HBV DNA\>ULN;
* HCV antibody(+); HIV antibody(+); active syphilitic patients;
* Uncontrolled blood pressure, defined as systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg;
* Stroke (cerebral vascular accident) or myocardial infarction within the 6 month period prior to baseline;
* History of other disease, metabolic dysfunction, physical examination finding, or historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications in the opinion of the investigator;
* Pregnancy or breastfeeding, or intention to become pregnant during the study;
* History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of RC28-E or to aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anaesthetic and anti-microbial drops used by the patient during the study;
* Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals) within the 3 month period prior to baseline.

Primary outcomes:
measure: Mean change from baseline in BCVA at week 48;
timeFrame: Baseline, week 48
Secondary outcomes:
measure: Average change in BCVA from baseline over the period week 36 through week 48;
timeFrame: Baseline, weeks 36, 40, 44 and 48.
measure: Proportion of subjects with q12w injection;
timeFrame: Baseline, week 48
measure: Proportion of subjects with q12w injection at week 48 within the subjects with no q8w injection need at week 16, week 20;
timeFrame: Week 16, 20, 48
measure: Proportion of subjects with gain in BCVA of 15/10/5/0 letters or more from baseline to week 48;
timeFrame: Baseline, week 48
measure: Mean change in CST from baseline to week 16, week 48;
timeFrame: Baseline, week 16, 48
measure: Average change in CST from baseline over the period week 36 through week 48;
timeFrame: Baseline, weeks 36, 40, 44 and 48.
measure: Proportion of subjects with presence of intraretinal fluid/subretinal fluid at week 16, week 48;
timeFrame: Baseline, week 16, 48
measure: Percentage of subjects with disease activity present at week 16;
timeFrame: Baseline, week 16
measure: Change in choroidal neovascularization (CNV) lesion size from baseline to week 12, week 48;
timeFrame: Baseline, week 12, 48
measure: Proportion of subjects with q8w treatment need at weeks 16, 20, 28, 32, 40, 44;
timeFrame: Weeks 16, 20, 28, 32, 40, 44
measure: Incidence and characteristics of ocular and systemic treatment emergent adverse events.
timeFrame: Baseline, week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
Study officials:
References: