An Open-label Study Evaluating Safety and Efficacy of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drops at Different Doses in Patients With Dry Eye
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change From Baseline in Frequency of Dry Eye Symptoms (SANDE)
研究概览
简要总结
The primary objective of this study was to assess the efficacy and safety of different doses of rhNGF when administered as eye drops to patients with dry eye.
详细描述
This is an open-label study evaluating safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops at different doses in patients with Dry Eye
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Male or female patients, ≥ 18 years old;
- •Required use of artificial tears for the treatment of Dry Eye within the 3 months prior to study enrolment;
- •Current use or recommended use of artificial tears for the treatment of Dry Eye;
- •Average VAS score for typical symptoms of Dry Eye (foreign body sensation, burning/stinging, itching, pain, stick feeling, blurred vision and photophobia) ≥ 25 mm;
- •Corneal staining score with lissamine green > 3 using the NEI corneal grading system in the worse eye (study eye);
- •Conjunctival staining score > 3 using the NEI conjunctival grading system in the worse eye (study eye);
- •Schirmer test without anaesthesia ≤ 10 mm/5 minutes in the worse eye (study eye);
- •Tear film break-up time (TBUT) ≤ 10 seconds in the worse eye (study eye);
- •A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period
排除标准
- •Patient not suitable to participate in the study in the opinion of the investigator;
- •Patient with a mild or moderate Dry Eye condition (severity level less than 3 according to the Report of the International Dry Eye Workshop -DEWS, 2007) if fourteen (14) patients with mild or moderate dry eye condition have been already enrolled in the current treatment group (Group 1 and Group 2 separately);
- •Patient has had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or has a clinically significant allergy to drugs, foods, amide local anaesthetics or other materials including commercial artificial tears containing Hypromellose (in the opinion of the investigator);
- •Use of topical cyclosporine, topical corticosteroids or any other topical medication for the treatment of dry eye in either eye within 30 days of study enrolment. Use of own artificial tears is allowed until Visit 2;
- •Any ocular disease other than Dry Eye requiring treatment with topical medications in either eye within 30 days of study enrolment;
- •Any active ocular infection or active inflammation in either eye unrelated to Dry Eye;
- •Presence or history of any systemic or ocular disorder, condition or disease that could possibly interfere with the conduct of the required study procedures or the interpretation of the study results;
- •Use of therapeutic or Refractive Contact lenses in either eye within 30 days of study enrolment;
- •History of ocular surgery in the study eye, including corneal refractive procedures, within 90 days of study enrolment;
- •Participation in another clinical study at the same time as the present and within 30 days of study enrolment;
- •History of drug, medication or alcohol abuse or addiction.
研究组 & 干预措施
Group 1 - rhNGF 20 μg/mL
(first planned dose): drop (35 μL) corresponding to 0.70 μg of rhNGF (recombinant human Nerve Growth Factor) was instilled into each eye twice a day (b.i.d.) every 12±2 h for a total daily dose of 2.8 μg (both eyes), for 28 consecutive days. The total dose was 78.4 μg/28 days.
干预措施: rhNGF 20 µg/mL (Drug)
Group 2 - rhNGF 4 μg/mL
after completion of Group 1 treatment, one drop (35 μL) corresponding to 0.14 μg of rhNGF (recombinant human Nerve Growth Factor) instilled into each eye b.i.d. every 12±2 h for a total daily dose of 0.56 μg, for 28 consecutive days. Total dose was 15.68 μg/28 days.
干预措施: rhNGF 4 µg/mL (Drug)
结局指标
主要结局
Change From Baseline in Frequency of Dry Eye Symptoms (SANDE)
时间窗: Baseline, Day 1, Day 8, Day 29 and Day 56
The SANDE is a short questionnaire to evaluate the frequency of ocular dryness and/or irritation symptoms. For the assessment, the patients mark on a 100 mm Visual Analogue Scale (VAS) line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks. The SANDE scores (0-100) will be then evaluated for frequency per day.
Change From Baseline in Severity of Dry Eye Symptoms (SANDE)
时间窗: Baseline, Day 1, Day 8, Day 29 and Day 56
The SANDE is a short questionnaire to evaluate the severity of ocular dryness and/or irritation symptoms. For the assessment, the patients mark on the 100 mm VAS line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left-hand end of the line to the point that the patient marks. The SANDE scores (0-100) will be then evaluated for severity. The higher the score, the worse the outcome.
Change From Baseline in Ocular Surface Vital Staining (National Eye Institute [NEI] Scale)
时间窗: Baseline, Day 1, Day 8, Day 29 and Day 56
The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal score of 15. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 and with a maximal score of 9 for the nasal and temporal conjunctiva. Staining was derived as the sum of scores in the various sectors. The higher the total score the more compromised is the ocular surface.
Change From Baseline in Tear Wetting Distance as Determined by Schirmer Tear Test I - Study Eye
时间窗: Baseline, Day 1, Day 8, Day 29 and Day 56
The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion prior to the instillation of any dilating or anaesthetic eye drops. The rounded tip of a standardized paper strip is inserted into the lower fornix of the eye, and the wetted length extending out from the lower lid is recorded after 5 min of eye closure. Both eyes could be tested at the same time. Changes from baseline in values of Schirmer's test type I are summarised by eye and evaluation visit, and stratified by severity level. The longer the wetted length the healthier the status of the eye. Only study eye's results are reported hereunder.
Number of Participants With Treatment-emergent Adverse Events (TEAEs),
时间窗: Throughout the study up to day 56
The treatment-emergent adverse events were recorded throughout the whole study.
次要结局
- Change From Baseline in Slit Lamp Examination(Baseline, Day 1, Day 8, Da 29 and Day 56)
- Change From Baseline in Tear Wetting Distance as Determined by Schirmer Tear Test II - Study Eye(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Tear Film Break-Up Time (TFBUT)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Corneal Fluorescein Staining(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Ocular Tolerability (Visual Analogue Scale, VAS)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Corneal Sensitivity to Contact (Cochet-Bonnet Aesthesiometry)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Intraocular Pressure (IOP)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Ocular Surface Disease Index (OSDI)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Visual Acuity (BCDVA)(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Number of Participants With a Change in Fundus Ophthalmoscopy(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Change From Baseline in Tear Film Osmolarity(Changes from baseline up to day 56±4)
- Change From Baseline in Conjunctival Impression Cytology for Goblet Cells' Count(Baseline, Day 1, Day 8, Day 29 and Day 56)
- Mean Frequency of Artificial Tears Use(Day 1-Day 8, Day 9-Day 29, Day 30-Day 56 intervals)