A Phase I/II, Double-blind, Placebo-controlled Study Assessing the Safety and Efficacy of AVX-012 Ophthalmic Solution in Subjects With Mild-to-moderate Dry Eye Syndrome
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 172
- 试验地点
- 21
- 主要终点
- The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye.
研究概览
简要总结
This is a first-in-human phase I/II randomized, double-blind, placebo (vehicle)-controlled, multicenter study to assess the Safety and Efficacy of AVX-012 Ophthalmic Solution in subjects with Mild-to-Moderate Dry Eye Syndrome.
The study consists of two parts (part A and part B):
详细描述
The study part A will be an early safety assessment of AVX-012 ophthalmic solution (Low dose and High dose AVX-012) administered three times per day (TID) when compared with the vehicle (placebo). Approximately 24 patients will be randomized 1:1:1 to study groups (Low dose AVX-012, High dose AVX-012, or placebo [vehicle]).
An independent safety committee will be in charge of assessing the safety of study treatments to proceed to part B.
The study part B will be an efficacy and safety assessment of the dose of AVX-012 ophthalmic solution selected in the study part A (Low dose or High dose AVX-012) administered three times a day (TID) and twice a day (BID) when compared with the vehicle (placebo). Approximately 148 patients will be randomized 1:1:1:1 to study groups (Low dose or High dose AVX-012 and placebo [vehicle], TID and BID).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
phase I/II, double-blind
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
- •Male or female subjects of at least 18 years of age.
- •Diagnosis of dry eye (by a health care professional) for at least 3 months prior to screening visit.
- •Normal lid anatomy.
- •Intraocular pressure less than 22 mmHg (inclusive) in each eye.
- •Best-corrected visual acuity measured by ETDRS in each eye of 20/200 (logMAR 1.0) or better.
- •Schirmer I test score of ≥ 3 mm to ≤ 9 mm/ 5 min (with anesthesia).
- •SANDE symptom score of 50 or more.
- •Total ocular staining of minimum 1 in Oxford scale with fluorescein and/or green lissamine.
- •Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.
排除标准
- •History of other than dry eye, ocular surface of moderate to severe Meibomian gland disease (grades +++ to ++++ [moderately to severely altered expressibility and secretion quality]: moderate symptoms with mild to moderate corneal staining, mainly peripheral; or marked symptoms with marked corneal staining, central in addition), chronic, or acute ophthalmic disease in either eye, including glaucoma, macular degeneration, clinically significant cataract (primary or secondary).
- •Best-corrected visual acuity score of 55 letters read or lower in each eye as measured by ETDRS (letters read method).
- •Previous history of drug or any ingredient hypersensitivity.
- •Intraocular or strabismus surgery or glaucoma laser surgery within the previous 6 months.
- •History of refractive surgery in either eye (e.g., radial keratotomy, PRK, LASIK, etc.).
- •Ocular trauma within the past 6 months.
- •Relevant ocular pathology judged by the investigator such as; eyelid anomalies, corneal disorders, metaplasia of the ocular surface, current filamentous keratitis, or corneal neovascularization.
- •Any history of herpes simplex or herpes zoster keratitis.
- •Ocular infection (bacterial, viral, or fungal)
- •Ocular medication of any kind, with the exception of artificial tears/gels/lubricants within the past 2 weeks of screening.
- •Cyclosporine treatment during the 6 months prior to enrolment.
- •Use of systemic medication that might cause dryness in the eye as a secondary effect (such as antihistaminics, hormone replacing therapies, etc.).
- •Use of contact lens
- •Use of additional artificial tears (other than study treatments) throughout the study, starting at screening visit.
- •Participation in an investigational drug or device trial within the 30 days previous to screening visit.
- •Any abnormality preventing reliable applanation tonometry of either eye.
- •Central corneal thickness greater than 600 μm by conventional pachymetry.
- •Signs of severe ocular surface diseases including corneal or conjunctival staining judged as severe by the investigator.
- •Clinically significant systemic disease including uncontrolled diabetes, myasthenia gravis, hepatic, renal, cardiovascular, endocrine disorders, previous cerebrovascular accident with a significant residual motor or sensory defect, progressive neurologic disorders (Parkinsonism, dementias, multiple sclerosis, unstable acquired seizure disorders) which might interfere with the study as judged by the investigator.
- •Any systemic disease or medication that might course with known dryness in the eye.
- •Changes of systemic medication that could have a substantial effect on intraocular pressure within 30 days prior to screening or anticipated during the study.
- •Any medical condition (systemic or ophthalmic) that may, in the opinion of the investigator, preclude the safe administration of the investigational product or safe participation in this study.
- •Pregnant or breastfeeding females or those with a positive pregnancy test.
- •All females of childbearing potential must have a negative urine pregnancy test result at screening, and also agree to abstain from sexual intercourse with a male partner or agree to use a medically acceptable method of birth control (such as condom, diaphragm or cervical/vault cap with spermicide) until 28 days post-treatment. Males should also agree to abstain from sexual intercourse with a female partner or agree to use a condom with spermicide until 28 days post-treatment.
研究组 & 干预措施
AVX-012 Opthalmic Solution Low dose
Phase I: AVX-012 ophthalmic solution Low dose administration three times per day (TID) for 7 days
Phase II: If the low dose of AVX012 is selected on phase I, AVX-012 ophthalmic solution Low dose administration three times per day (TID) and two times per day (BID) for 28 days
干预措施: AVX012 Ophthalmic Solution Low dose (Drug)
AVX-012 Opthalmic Solution High dose
Phase I: AVX-012 ophthalmic solution High dose administration three times per day (TID) for 7 days
Phase II: If the high dose of AVX012 is selected on phase I, AVX-012 ophthalmic solution High dose administration three times per day (TID) and two times per day (BID) for 28 days
干预措施: AVX012 Ophthalmic Solution High dose (Drug)
Placebo (Vehicle) Opthalmic Solution
Phase I: Placebo ophthalmic solution administration three times per day (TID) for 7 days
Phase II: Placebo ophthalmic solution administration three times per day (TID) and two times per day (BID) for 28 days
干预措施: Placebo (vehicle) (Drug)
结局指标
主要结局
The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye.
时间窗: 28 days (+7 days)
Percentage of patients achieving an improvement ≥ 20 points in the Symptom Assessment in Dry Eye (SANDE) questionnaire according to the different dosing frequencies (TID and BID).
The objective of part A is to evaluate the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.
时间窗: 7 days (+1 day)
Evaluation of vital signs (blood pressure and heart rate), laboratory analyses (haematology, biochemistry, and urine pregnancy test), best-corrected visual acuity (ETDRS), corneal anaesthesia (Cochet-Bonnet), intraocular pressure, biomicroscopy/staining (fluorescein), and ophthalmoscopy (dilated).
次要结局
- Confirm the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.(28 days (+7 days))
- Change from baseline in corneal staining score(28 days (+7 days))
- Change from baseline in tear film break up time score(28 days (+7 days))
- Change from baseline in conjunctival staining score(28 days (+7 days))
- Change from baseline in Schirmer I test score(28 days (+7 days))