A 24 Week Phase Ib/II, Multicenter, Randomized, Controlled, Parallel Group, Dose Ranging Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of 2 Doses (60, 180 µg/ml) of rhNGF Solution vs Vehicle in Patients With RP.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 5
- 主要终点
- Number of Participants With Serious and Non-Serious Adverse Events
研究概览
简要总结
The primary objective of the study is to assess the safety and tolerability of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution administered over 6 months versus a vehicle control in patients with typical retinitis pigmentosa. The secondary objective of this study is to attempt to show a dose response by assessing the potential efficacy of the rhNGF dose regimens for improving or slowing the deterioration of visual function outcomes at 3 and 6 months. During a 6 month follow-up period patients will be monitored to determine if there is evidence of a persistent biological effect after discontinuation of the study treatment.
详细描述
This is a 24-week phase Ib/II, multicenter, randomized, double-masked, vehicle controlled, parallel-group, dose-ranging study with a 24-week follow-up period to evaluate the safety and potential efficacy of two doses (60 μg/ml and 180 μg/ml) of recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in patients with typical retinitis pigmentosa (RP).
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)
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
- •Patients 18 years of age or older.
- •Patients with typical forms of RP characterized by the following clinical features: classic fundus appearance (i.e. intraretinal pigment deposits, thinning and atrophy of the retinal pigment epithelium (RPE) in the mid- and far peripheral retina, with relative RPE preservation in the macula, waxy pallor of the optic disc, attenuation of the retinal vessels), reduced and delayed ERG responses, visual field constriction
- •Best corrected distance visual acuity (BCDVA) score of ≥ 48 ETDRS letters (equivalent to 20/100 Snellen, +0.7 LogMar, or 0.2 decimal fraction) in either eye at the time of study enrollment.
- •Documented evidence of disease progression within the 12 months prior to enrollment in the study as demonstrated by ERG (≥20% decrease in b wave amplitude in scotopic conditions or ≥25% in photopic conditions) and/or visual field testing (≥10% of Goldman Visual Field expressed as area square or ≥3 dB decrease of Humphrey Visual Field Mean Deviation).
- •Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her impartial witness 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 impartial witness must have been approved by the Ethics Committee (IEC) for the current study.
- •Patients must have the ability and willingness to comply with study procedures.
排除标准
- •Patients with atypical, early onset (first decade) or syndromic forms of RP (e.g. paravenous, pericentral sector or unilateral RP, Leber's congenital amaurosis, Refsum disease, Usher syndrome, Bardet-Biedl syndrome, etc).
- •Patients with non-recordable 30 Hz cone ERG in either eye.
- •Patients with Goldman visual field less than 20º using the V4e target or residual central visual field less than -35 dB as evaluated by the 24-2 program of the Humphrey visual field in either eye.
- •Evidence of an active ocular infection in either eye.
- •History of uveitis or evidence of intraocular inflammation in either eye.
- •History or evidence of glaucoma or an intraocular pressure (IOP) greater than or equal 21 mmHg in either eye at the time of study enrollment.
- •Patients with foveal thickness ≥ 250 micrometers (as evaluated with OCT).
- •History of cystoid macular oedema or presence of cystoid macular oedema on OCT at the time of study enrolment.
- •Anterior segment abnormalities or media opacities obscuring the view of the posterior pole in either eye.
- •History of any ocular surgery (including laser or refractive surgical procedures) in either eye within the 120 days before study enrolment. Ocular surgery will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period.
- •Treatment with corticosteroids (systemic, periocular or intravitreal) or any other non-approved, experimental, investigational or neuroprotectant therapy (systemic, topical, intravitreal) in either eye within 90 days of study enrollment.
- •Use of any medication other than the study medication for the treatment of ocular diseases with the exception of artificial tears during the study period.
研究组 & 干预措施
rhNGF 60µg/ml
rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
干预措施: rhNGF 60 µg/ml eye drops solution (Drug)
rhNGF 180 µg/ml
rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
干预措施: rhNGF 180 µg/ml eye drops solution (Drug)
Vehicle
Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Serious and Non-Serious Adverse Events
时间窗: up to 48 weeks
Twenty-seven patients of the Safety population experienced at least one treatment-emergent adverse event, 11 patients in the rhNGF 60 μg/ml arm, 13 patients in the rhNGF 180 μg/ml arm and 3 patients in the vehicle arm.
Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart)
时间窗: Weeks 1, 2, 6, 12, 24, 36, 48
Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters.
Change in Ocular Tolerability - VAS
时间窗: Weeks 1, 2, 6, 12, 24
A global ocular discomfort score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. For ocular tolerability analysis, mixed models for repeated measures were applied using various ocular tolerability parameters as response variable, treatment, visit and treatment by visit interaction as fixed effects, and baseline value as covariate.
Change in Intraocular Pressure (IOP)
时间窗: Weeks 2,12 and 24
Intraocular Pressure was measured using either Goldmann applanation tonometry or a handheld applanation tonometer (e.g. Tonopen) after the instillation of a topical anesthetic.IOP was assessed for each eye at day 0 and at week 2, 12 and 24
Presence of Anti-NGF Antibodies
时间窗: At Day 0 and at week 24
Anti-NGF antibodies tests were performed at screening and at the end of treatment
External Ocular Examination
时间窗: Day 0, Weeks 1, 2, 6, 12, 24
External ocular examinations were done to assess, for each eye and at each visit, the motility of extraocular muscles, appearance and function of the eyelids.
Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination
时间窗: Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48
Slit Lamp Examination (SLE) (Biomicroscopy) was performed before the instillation of any dilating or anesthetic eye drops or fluorescein agents. SLE was executed to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber.
Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy
时间窗: Day 0, Weeks 12, 24 and 48
Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head.
次要结局
- Microperimetry(Day 0, Weeks 12, 24, 36 and 48)
- Change From Baseline in Humphrey Visual Field 24-2(Weeks 12, 24, 36 and 48)
- Change in Goldmann Visual Field(Weeks 12, 24, 36 and 48)
- Binocular Estermann Visual Field(Day 0, Weeks 12, 24, 36 and 48)
- Ocular Coherence Tomography (OCT)(Day 0, Weeks 12, 24, 36 and 48)
- Change From Baseline in Contrast Sensitivity(Weeks 12, 24, 36 and 48)
- Fundus Imaging(Day 0, Weeks 24 and 48)
- Electrorethinogram (ERG)(Day 0, Weeks 12, 24, 36 and 48)