A 4 Weeks, Phase II, Multicenter, Randomized, Double-masked, Vehicle-controlled, Parallel Group Study With 12 Weeks of Follow-up to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution vs Vehicle in Moderate to Severe Dry Eye.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 261
- 试验地点
- 12
- 主要终点
- Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set
研究概览
简要总结
The objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20 μg/ml concentration administered two or three times daily for 4 weeks in patients with moderate to severe dry eye.
详细描述
This is a 4 weeks, Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with 12 weeks of follow-up, designed to perform dose-ranging and to evaluate safety and efficacy of recombinant human Nerve Growth Factor (rhNGF) eye drops solution versus vehicle, in patients with moderate to severe dry eye (DE).
Test product is rhNGF 20 μg/ml; reference product is vehicle. Test and reference will be instilled in both eyes according to the following scheme:
Group 1: one drop of rhNGF 20 μg/ml is instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).
Group 2: one drop of rhNGF 20 μg/ml is instilled in both eyes two times daily (in the morning and in the evening) plus one drop (40 μL) of vehicle (placebo) is instilled in both eyes once daily in the afternoon.
Group 3: one drop (40 μL) of vehicle (placebo) is instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double masked
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥ 18 years
- •Patients with moderate to severe dry eye characterized by the following clinical features:
- •Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system > 3
- •SANDE questionnaire >25 mm
- •Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes
- •Tear film break-up time (TFBUT) < 10 seconds in the worse eye
- •The same eye (eligible eye) must fulfill all the above criteria
- •Patients diagnosed with dry eye at least 6 months before enrolment (current use or recommended use of artificial tears for the treatment of Dry Eye)
- •Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in both eyes at the time of study enrolment
- •If a female of childbearing potential, have a negative pregnancy test
- •Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
- •Patients must have the ability and willingness to comply with study procedures.
排除标准
- •Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments;
- •Evidence of an active ocular infection, in either eye
- •Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study
- •History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
- •Intraocular inflammation defined as Tyndall score >0
- •History of malignancy in the last 5 years
- •Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, thyroid malfunction..) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or with a condition incompatible with the frequent assessment required by the study
- •Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anaesthetics or other materials including commercial artificial tears (in the opinion of the investigator)
- •Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:
- •are currently pregnant or,
- •have a positive result at the urine pregnancy test (Baseline/Day 0) or,
- •intend to become pregnant during the study treatment period or,
- •are breast-feeding or,
- •are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods
- •Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
- •Use of topical cyclosporine, topical corticosteroids or any other topical drug for the treatment of dry eye in either eye within 30 days of study enrolment.
- •Contact lenses or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
- •History of drug addiction or alcohol abuse
- •Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit
- •Participation in a clinical trial with a new active substance during the past 6 months
- •Participation in another clinical trial study at the same time as the present study.
研究组 & 干预措施
rhNGF 20 μg/ml TID
One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
干预措施: rhNGF 20 μg/ml (Drug)
rhNGF 20 μg/ml BID + vehicle OD
One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours)
干预措施: rhNGF 20 μg/ml + vehicle (Drug)
Vehicle TID
Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours)
干预措施: Vehicle (Other)
结局指标
主要结局
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set
时间窗: Baseline, week 4
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set
时间窗: Baseline, week 4
The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion
次要结局
- Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set(Baseline, week 4)
- Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set(Baseline, week 4)
- Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set(Baseline, week 4)
- Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set(Aat baseline and weeks 4, 8, 12 and 16)
- Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set(Baseline, week 4)
- Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set(Baseline, week 4)
- Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set(Baseline, week 4)
- Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set(Baseline, week 4)
- Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set(Baseline, week 4)
- Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set(At week 4)
- Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set(At week 4)
- Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set(At weeks 4, 8, 12 and 16)
- Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set(At weeks 4, 8, 12 and 16)
- Patient Global Impression of Change (PGIC) - Full Analysis Set(At baseline and weeks 4, 8, 12 and 16)
- Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set(At weeks 4, 8, 12 and 16)
- Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set(Baseline, week 4)
- Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set(Baseline, week 4)
- Patient Global Impression of Change (PGIC) - Per Protocol Set(At weeks 4, 8, 12 and 16)