CTRI/2022/04/041823尚未招募2 期
TGF-BETa 2 antisense ISTH0036 for the Treatment of diabetic macular Edema (DME) and neovascular age-related maculaR degeneration (nAMD) as Monotherapy or in combination with Aflibercept The “BETTER†Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- OCT CMT at 7 months vs. baseline. For treatment naïve patients, improvement versus BL will be analyzed, for anti-VEGF pre-treated patients, maintenance, or improvement of CMT versus BL will be assessed.
研究概览
简要总结
Considering the efficacy andsafety findings demonstrated in the phase 1 study and the preclinical program,this Phase 2a multicenter study of treatment-naïve and pretreated patients withDME and nAMD is being performed to assess effects of ISTH0036 as monotherapy orin combination with Aflibercept on macular edema, CNV and fibrosis over aperiod of 7 months (plus additional 2 mo of safety observation).[
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients eligible for inclusion in this study must meet all the following criteria:
- •Patients must provide written informed consent before any study related procedures are performed.
- •Patients must be ≥18 yrs in the DME cohort and ≥ 50 in the nAMD cohort at Screening.
- •Study eye nAMD:
- •Active CNV lesions secondary to nAMD (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at Screening in treatment naïve nAMD arm.
- •About 50% of the patients in the AMD treatment naïve group should have classic or predominantly classic CNV / Type II CNV or hemorrhage
- •Pretreated CNV lesions secondary to nAMD (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at Screening in pretreated nAMD.
- •About 50% of the patients should be included with SHRM present on OCT despite anti-VEGF therapy or hemorrhage present at initial diagnosis/ therapy start.
- •Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening with CMT ≥305 μm in women, and ≥320μm in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment naïve nAMD arm.
- •For treatment naïve patients, BCVA between 83 and 23 letters, inclusive, in the study eye at Screening and Baseline using early treatment diabetic retinopathy study (ETDRS) testing.
- •For Treatment naïve and VEGF primed group: Treatment naïve nAMD in study eye
- •For VR-group: Dry or ≤50 micrometer SRF in vertical extension after receiving 1-6 anti-VEGF injections.
- •Diagnosis no longer than 9 months before Baseline Study eye DME:
- •Active CME secondary to diabetes in the study eye at Screening in treatment naïve DME.
- •Intra- and/or subretinal fluid affecting the central subfield of the study eye at Screening with CMT ≥305 μm in women, and ≥320μm in men or with a center point thickness of >260 in women and >270 micrometer in men as measured by SD-OCT in treatment naïve DME arm.
- •Moderate to severe NPDRP assessed via ETDRS severity scale and mild PDRP (with 1 NVE) in study eye (diabetic retinopathy severity scale DRSS 43-61)
- •Absence of prior PRP treatment
- •For Treatment naïve group: Treatment naïve DME in study eye
- •For VR-group: History of CME secondary to diabetes in the study eye with complete resolution of IRF and/or SRF or a ≥20% reduction in CMT secondary to diabetes after receiving 1-6 monthly anti-VEGF injections over the last 9 months.
排除标准
- •Patients meeting any of the following criteria are not eligible for inclusion in this study.
- •Ocular conditions
- •Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Baseline.
- •Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 35 ETDRS letters at Screening (except when due to conditions whose surgery may improve visual acuity, e.g., cataract).
- •Study eye nAMD
- •nAMD diagnosed for more than 9 months
- •Poor quality of SD-OCT images at Screening or Baseline.
- •Central subfield of the study eye affected by geographic atrophy assessed by OCT, color fundus photography (CFP) and fundus autofluorescence (FAF) at Screening.
- •Subretinal blood affecting the central subfield and/or ≥ 50% of the lesion of the study eye at Screening.
- •Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than nAMD, that, in the judgment of the investigator, could require medical or surgical intervention during the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product.
- •Structural damage within 0.5-disc diameter of the center of the macula in the study eye, e.g., vitreomacular traction, epiretinal membrane, retinal pigment epithelium (RPE) rip/tear scar, laser burn, at the time of Screening that in the investigator’s opinion could preclude visual function improvement with treatment.
- •Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline.
- •Uncontrolled glaucoma in the study eye defined as IOP > 25 mmHg on medication or according to the investigator’s judgment at Screening or Baseline.
- •Aphakia and/or complete absence of the posterior capsule in the study eye at Screening.
- •For Treatment naïve and VEGF primed group: Any prior treatment for nAMD in study eye
- •For VR-group: > 50 micrometer SRF in vertical extension after receiving 1-6 anti-VEGF injections over the last 9 months
- •For VR-group: > 6 anti-VEGF injections Study eye DME
- •Treatment requiring DME diagnosed for more than 9 months
- •Poor quality of SD-OCT images.
- •Concomitant conditions or ocular disorders in the study eye, including retinal diseases other than DME, that, in the judgment of the investigator, could require medical or surgical intervention during the study to prevent or treat visual loss that might result from that condition, or that limits the potential to gain visual acuity upon treatment with the investigational product.
- •Moderate and severe PDRP requiring PRP in study eye
- •Prior PRP treatment in study eye
- •For Treatment naïve group: Any prior treatment for DME in study eye
- •For VR-group: <20% reduction in CMT after receiving 1-6 monthly anti-VEGF injections over the last 9 months after diagnosis.
- •For VR-group: > 6 anti-VEGF injections Ocular treatments (study eye)
- •Patient has received any investigational treatment for nAMD or DME (other than vitamin supplements) in the study eye at any time.
- •Intraocular or periocular use of corticosteroids in the study eye during the 6-month period prior to Baseline.
- •Previous penetrating keratoplasty or vitrectomy at any time prior to Baseline.
- •History or evidence of the following in the study eye within the 90-day period prior to Baseline: • Intraocular or refractive surgery.
- •â€¢ Previous submacular surgery, other surgical intervention, or laser treatment for nAMD or DME including photodynamic therapy (PDT) and focal laser treatment.
- •Systemic conditions or treatments
- •End stage renal disease requiring dialysis or renal transplant.
- •Systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol) used during the 6-month period prior to Baseline.
- •Participation in an investigational drug, biologic, or device study within 30 days or the duration of 5 half-lives of the investigational product (whichever is longer) prior to Baseline.
- •Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary.
- •Systemic anti-VEGF therapy at any time.
- •Stroke or myocardial infarction in the 6-month period prior to Baseline.
- •Uncontrolled blood pressure defined as a systolic value ≥ 170 mmHg or diastolic value ≥ 110 mmHg at Screening or Baseline.
- •(In case there is an elevated blood pressure measurement, it should be repeated after 20 minutes.
- •If the repeat measurement is elevated, then the patient is not eligible to be enrolled into the study).
- •History of a medical condition (disease, metabolic dysfunction with exception of type 1 or 2 diabetes mellitus, physical examination finding, or clinical laboratory finding) that, in the judgment of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product.
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- •History of hypersensitivity to any component of the test article, control article, or clinically relevant sensitivity to fluorescein dye, as assessed by the investigator Other
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test.
- •Women of childbearing potential defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization at Baseline, unless they are using effective methods of contraception during dosing of study treatment.
- •Effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient).
- •Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
- •â€¢ Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before Baseline.
- •In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
- •â€¢ Male sterilization (at least 6 months prior to Baseline).
- 另有 6 项未显示
结局指标
主要结局
OCT CMT at 7 months vs. baseline. For treatment naïve patients, improvement versus BL will be analyzed, for anti-VEGF pre-treated patients, maintenance, or improvement of CMT versus BL will be assessed.
时间窗: 9 Months
次要结局
- Number and type of adverse events (AE) in all groups(Incidence and progression of cataract using LOCS III score in patients treated with ISTH0036)
研究者
研究点 (3)
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