NCT05532735已完成2 期
Open-label, Dose Ascending Safety, Tolerability, and Proof of Concept Study to Evaluate the Use of ANXV (Human Recombinant Annexin A5) in the Treatment of Subjects With Recently Diagnosed Retinal Vein Occlusion
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- Safety - Treatment Emergent Adverse Events
研究概览
简要总结
Open-label, dose ascending safety, tolerability, and proof of concept study to evaluate the use of ANXV (human recombinant Annexin A5) in the treatment of subjects with recently diagnosed Retinal Vein Occlusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have given written informed consent (signed and dated), and any authorizations required by local law and be able to comply with all study requirements
- •Male or female, ≥18 years of age at the time of informed consent
- •Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., ≥6 weeks post bilateral salpingectomy, bilateral oophorectomy with or without hysterectomy) or post-menopausal (12 months of spontaneous amenorrhea in females > 55years of age or, in females ≤55 years, or 12 months of spontaneous amenorrhea without an alternative medical, or 12 months with an elevated Follicle Stimulating Hormone (FSH) level Males must either be surgically sterile or abstinent*, or if engaged in sexual relations with a female of child-bearing potential, the subject or the subject's non-pregnant female partner must use a highly effective contraception method from the time of signing the Informed Consent Form (ICF) until at least 30 days after the last dose of study drug; Refer to Section 10.3 for acceptable methods
- •*Abstinence is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods). Declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception (Section 10.3).
- •Onset of symptoms of Retinal Vein Occlusion within 23 days prior to informed consent
- •The criterion has been removed
- •The criterion has been removed
- •Clear ocular media and adequate pupillary dilation in the Study Eye to permit high quality retinal imaging
- •Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 72 hours prior to study visits
- •A negative rapid SARS-CoV-2 (COVID) test on Day 1 prior to initiation of study drug infusion
排除标准
- •Subjects will not be eligible if they have any of the following criteria:
- •Study Eye only:
- •A severe (≥0.9 log, Grade 3+ or worse) Relative Afferent Pupillary Defect (RAPD)
- •Evidence of deep intraretinal hemorrhage involving the center 1mm of the macula
- •Evidence of neovascularization
- •Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results, compromise protocol assessments or are likely to require intervention during the study, including, but not limited to, atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hard exudate plaque, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., Age-related Macular Degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia)
- •Laser photocoagulation in the study eye within the preceding 6 months prior to the Screening Visit
- •Receipt within the past 6 months prior to the Screening Visit of any intraocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study, unless approved by Medical Monitor or Sponsor
- •Recent (6 months) history, or current evidence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus), unless approved by Medical Monitor or Sponsor
- •Fellow Eye:
- •BCVA in the Fellow eye of ≤70 ETDRS letters (approximately 20/40 or less), unless approved by the Medical Monitor or the Sponsor
- •Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
- •Known hypersensitivity or allergy to fluorescein (e.g., bronchospasm, rash, etc.) or to any component of the study products or a contraindication to dilation of the pupil or fixed pupils; mild allergies without angio-edema or treatment need may be acceptable if deemed not to be of clinical significance (including but not limited to allergy to animals or mild seasonal hay fever)
- •An IOP greater than 24 mmHg that is not controlled with medication or surgery at the time of the Screening Visit
- •Recent (6 months) history of, or presence of uveitis, presence of intraocular inflammation (history of blepharitis is not exclusionary), current ocular infection
- •Unwillingness or inability to attend all study visits and/or perform all procedures/tests/examinations, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
- •Any medical or surgical procedure or trauma within 4 weeks prior to the day of Treatment 1 (study drug administration), or planned major surgery within the duration of the study through Day 120, unless approved by Medical Monitor or Sponsor
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
- •Prior exposure to a recombinant Annexin A5
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to biologics (for example systemically administered recombinant proteins/peptides; a similar drug class to ANXV)
- •Uncontrolled hypertension (systolic > 180 mmHg or diastolic > 110 mmHg)
- •Current use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib) or corticosteroids, approved or 5 half-lives of investigational agent
- •Diagnosed untreated systemic metastasis malignancy
- •A current systemic infection or inflammation that may require antiviral or antimicrobial therapy that will not be completed prior to Screening Visit, or that in the opinion of the Investigator and with concurrence of the Medical Monitor may either put the subject at risk or may influence the results of the study, or the subject's ability to participate in the study
- •Treatment with another investigational drug, biological agent, or device within 3 months of Screening Visit, or 5 half-lives of investigational agent, whichever is longer or planned participation in an investigational trial from signing ICF through Day 120
- •History of thromboembolic events or deep venous thrombosis within 3 months of Screening Visit
- •Current use of anticoagulant medication (any medications that might have effect on coagulation, hemostasis, and platelets); low dose aspirin allowed prior to informed consent but must be stopped at the time of consent; may begin again 1 day post Treatment 5 infusion
- •Current daily use of benzodiazepines (intermittent use permissible with Medical Monitor or Sponsor approval)
- •Clinically significant abnormal coagulation parameters at baseline
- •The criterion has been removed from the protocol
- •History of autoimmune disease with anticipated presence of persistent Annexin A5 antibodies, e.g., antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet disease or systemic sclerosis
- •Inherited blood disorder (e.g. sickle cell disease, thalassemia)
- •History of unstable coronary artery disease or cerebrovascular accident within the last 3 months
- •GFR below 70 mL/min at baseline
- •Current drug or alcohol abuse, current excessive smoking (i.e., ≥ 20/day)
- •Known history of or positive test for hepatitis C or chronic hepatitis B
- •Class III obesity (Body Mass Index ≥ 40kg/m2), at the time of informed consent (Sponsor may accept eligibility for a subject with higher Body Mass Index
研究组 & 干预措施
2 mg ANXV
Experimental
ANXV (human recombinant Annexin A5), infusion, 2 mg daily during five days.
干预措施: ANXV (Biological)
4 mg ANXV
Experimental
ANXV (human recombinant Annexin A5), infusion, 4 mg daily during five days.
干预措施: ANXV (Biological)
1 mg ANXV
Experimental
ANXV (human recombinant Annexin A5), infusion, 1 mg daily during five days.
干预措施: ANXV (Biological)
6 mg ANXV
Experimental
ANXV (human recombinant Annexin A5), infusion, 6 mg daily during five days.
干预措施: ANXV (Biological)
8 mg ANXV
Experimental
ANXV (human recombinant Annexin A5), infusion, 8 mg daily during five days.
干预措施: ANXV (Biological)
结局指标
主要结局
Safety - Treatment Emergent Adverse Events
时间窗: 120 days
Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Safety - Anti-drug antibodies
时间窗: 120 days
Incidence and titer of anti-drug antibodies (ADA) to ANXV pre- and post-administration
次要结局
- Safety - Best Corrected Visual Acuity (BCVA)(120 days)
- Safety - laboratory parameters(15 days)
- Safety - vital signs Blood Pressure(15 days)
- Safety - vital signs Heart rate(15 days)
- Safety - vital signs Weight(15 days)
- Safety - vital signs Body Temperature(15 days)
- Safety - vital signs Respiratory rate(15 days)
- Safety - vital signs Pulse oximetry(15 days)
- Safety - ECG(15 days)
- Safety - ANXV anti-drug antibodies Persistence(12 months)
- Safety - ANXV anti-drug antibodies Titer(12 months)
- Efficacy - Microperimetry Change from baseline(120 days)
- Efficacy - Microperimetry Stimulus points(120 days)
- Efficacy - Need for rescue treatment with anti Vascular Endothelial Growth Factor (aVEGF) therapy(29 days)
- Ischemic Index(120 Days)
- Efficacy - Microperimetry Improvement over baseline(120 days)
- Efficacy - Microperimetry Incremental loss(120 days)
- Efficacy - Microperimetry Improvement of ≥7dB(120 days)
- Efficacy - Microperimetry MMP negative-5 responders(120 days)
- Efficacy - BCVA Improvement(120 days)
- Pharmacokinetic (PK) profile(5 days)
- Efficacy - BCVA Improvement or letter score ≥78(120 days)
- Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) SD-OCT(120 days)
- Safety - Slit lamp(120 days)
- Safety - Gonioscopy(120 days)
- Efficacy - Spectral Domain Optical Coherence Tomography / Spectral Domain Optical Coherence Tomography Angiography (SD-OCT/OCTA) OCTA(120 days)
- Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Size of Retinal Area of Non-Perfusion(120 days)
- Efficacy - Ultra-Wide Field Fluorescein Angiography (UWF-FA) Conversion from non-ischemic RVO to ischemic RVO(120 days)
研究者
研究点 (6)
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