A Prospective, Randomized, Double-Masked, Vehicle Controlled, Phase 2 Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide Topical Ophthalmic Solution in Subjects With Leber's Hereditary Optic Neuropathy (LHON)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Open Label Extension: Incidence of Ocular TEAEs
研究概览
简要总结
This is a Phase 2, prospective, randomized, double-masked, vehicle controlled, single-center study in approximately 12 subjects with LHON to evaluate safety, tolerability and efficacy of elamipretide (MTP-131) topical ophthalmic solution in this patient population. At the conclusion of 52 weeks of treatment, subjects will be offered the opportunity to enter an Open Label Extension for up to 48 additional weeks of treatment.
详细描述
This was a prospective, randomized, double-masked (DM), vehicle-controlled, single-center study plus open label extension period (OLE) in which approximately 12 subjects with LHON having the genetic mtDNA mutation m.11778G>A were randomized in a masked manner into 1 of 3 groups in a 1:1:1 ratio: one drop of elamipretide 1.0% topical ophthalmic solution twice daily (BID) in the: left eye, right eye, or both eyes.
After completion of the 52-week treatment period or the Week 56 follow-up period, subjects were invited to participate in the OLE period for up to 108 weeks. During the OLE participants received 1% topical opthalmic elamipretide in both eyes (OU) daily. If a subject did not consent to the OLE, he/she completed the study at the Week 56 (±7 days) visit. There were 4 periods in this study: (1) screening period (up to 6 weeks); (2) double-masked treatment period (52 weeks); (3) OLE period (up to 108 weeks), and (4) follow-up period (4 weeks) after completion of End-of-Treatment (EOT) visit.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 and ≤ 50 years old at the time of loss of vision in the second eye.
- •Able to provide informed consent and willing to comply with all study visits and examinations
- •Diagnosis of LHON based on clinical and ophthalmic functional/anatomic test findings, and satisfactory documentation of the mitochondrial DNA mutation m.11778G>A
- •Loss of vision in both eyes of ≥1 year and ≤10 years at the time of the Screening Visit and current clinically stable visual function (as assessed by the Investigator)
- •Able to self-administer eye drops as demonstrated at screening or having a care provider who can do so
- •Documentation of having satisfactorily completed at least two previous Humphrey automated visual field tests prior to screening.
- •Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the informed consent form
排除标准
- •Any other ocular pathology requiring treatment with prescription topical ophthalmic drops (e.g., glaucoma, dry eye)
- •Cup to disc ratio of > 0.8 in either eye
- •Media opacity, suboptimal pupillary dilatation, or refractive error that interferes with adequate retinal imaging
- •Known to be immunocompromised or receiving systemic immunosuppression
- •Any disease or medical condition that in the opinion of the Investigator would prevent the subject from participating in the study or might confound study results
- •Participation in other investigational drug or device clinical trials within 30 days prior to enrollment, or planning to participate in any other investigational drug or device clinical trials within 30 days of study completion
- •Women who are pregnant or lactating
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Group 1
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to the left eye (OS) and one drop of vehicle topical ophthalmic solution BID in the fellow eye
干预措施: elamipretide (MTP-131) 1% topical ophthalmic solution (Drug)
Group 1
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to the left eye (OS) and one drop of vehicle topical ophthalmic solution BID in the fellow eye
干预措施: Vehicle topical ophthalmic solution (Drug)
Group 2
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to the right eye (OD) and one drop of vehicle topical ophthalmic solution BID in the fellow eye
干预措施: elamipretide (MTP-131) 1% topical ophthalmic solution (Drug)
Group 2
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to the right eye (OD) and one drop of vehicle topical ophthalmic solution BID in the fellow eye
干预措施: Vehicle topical ophthalmic solution (Drug)
Group 3
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).
干预措施: elamipretide (MTP-131) 1% topical ophthalmic solution (Drug)
OLE
One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).
干预措施: elamipretide (MTP-131) 1% topical ophthalmic solution (Drug)
结局指标
主要结局
Open Label Extension: Incidence of Ocular TEAEs
时间窗: Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
Open Label Extension: The incidence of ocular treatment emergent adverse events (TEAEs).
Double Masked Period: Incidence of Ocular TEAEs
时间窗: Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit)
The incidence of ocular treatment emergent adverse events (TEAEs).
OLE: Severity of Ocular TEAEs
时间窗: Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
The severity of ocular treatment emergent adverse events (TEAEs).
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale
时间窗: Assessed at each visit from Baseline from Week 68 to Week 160 (follow-up visit).
Open Label Extension Period: Best corrected visual acuity (BCVA) using the using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale by visit. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).
Double Masked Period: Severity of Ocular TEAEs
时间窗: Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit)
The severity of ocular treatment emergent adverse events (TEAEs).
Double Masked Period: Best Corrected Visual Acuity (BCVA)
时间窗: Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit)
Double Masked Period: Best corrected visual acuity (BCVA) using the using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale by visit. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).
次要结局
- Open Label Extension Period: PhNR-ERG B-wave Amplitude(Assessed at each visit from Baseline from Week 68 to Week 160)
- Double Masked Period: PhNR/B-wave Amplitude Ratio(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Open Label Extension Period: PhNR Amplitude(Assessed at each visit from Baseline from Week 68 to Week 160)
- Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio(Assessed at each visit from Baseline from Week 68 to Week 160)
- Open Label Extension Period: VFQ-39 Composite Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Open Label Extension Period: VFQ-39 Ocular Pain Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Double Masked Period: PhNR Amplitude(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude(Assessed at each visit from Baseline from Week 68 to Week 160)
- Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude(Assessed at each visit from Baseline from Week 68 to Week 160)
- Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Double Masked: VFQ-39 Composite(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Double Masked Period: Color Discrimination - Number of Plates(Assessed at each visit from Baseline to Week 56 (follow-up visit))
- Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit(Assessed at each visit from Baseline to Week 56 (follow-up visit))
- Open Label Extension Period: Change From Baseline in Retinal Ganglion Cell Layer Thickness(Assessed at Baseline, Week 148,)
- Double Masked: VFQ-39 Distance Activities Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted)(Assessed at each visit from Baseline from Week 68 to Week 160)
- Double Masked: VFQ-39 General Vision Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked: VFQ-39 Ocular Pain Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Open Label Extension Period: VFQ-39 Near Activities(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III(Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.)
- Open Label Extension Period: VFQ-39 General Health Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit(Assessed at each visit from Baseline from Week 68 to Week 160)
- Double Masked Change From Baseline in Retinal Ganglion Cell Layer Thickness(Assessed at Baseline and Week 52 (end-of-treatment visit))
- Open Label Extension Period: VFQ-39 General Vision Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked Period: Mean Retinal Nerve Fiber (RNFL) Layer Thickness(Assessed at Baseline and Week 52 (end-of-treatment visit))
- Open Label Extension Period: Retinal Nerve Fiber Layer Thickness(Assessed at Baseline, Week 148)
- Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit(Assessed at each visit from Baseline from Week 68 to Week 160)
- Open Label Extension Period: VFQ-39 Distance Activities Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Open Label Extension Period: VFQ-39 Social Functioning Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked: VFQ-39 Near Activities Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline(Assessed at each visit from Baseline from Week 68 to Week 160)
- Open Label Extension Period:VFQ-39 Dependency Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Open Label Extension Period: VFQ-39 Color Vision Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye(Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit))
- Double Masked: VFQ-39 Social Functioning Score.(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Open Label Extension Period: VFQ-39 Role Difficulties Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Open Label Extension Period: Intraocular Pressure (IOP)(Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit))
- Open Label Extension Period: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes(Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit))
- Double Masked: VFQ-39 Mental Health Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked: VFQ-39 Role Difficulties Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked: VFQ-39 Peripheral Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- OLE: Slit Lamp Examination (SLE)-Vehicle Eye(Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit))
- Open Label Extension Period: VFQ-39 Mental Health Score(Assessed at Baseline, Week 160 (End of OLE Period))
- Double Masked: VFQ-39 Dependency Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked: VFQ-39 Color Vision Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Double Masked Period: Change in Intraocular Pressure (IOP)(Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit))
- OLE: Slit Lamp Examination (SLE)-Elamipretide Eye(Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit))
- Double Masked: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes(Assessed at each visit: Baseline, Day 5 Visit, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (End of treatment visit) and Week 56 (Follow up visit))
- Double Masked: VFQ-39 General Health Score(Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit))
- Open Label Extension Period: Visual Function Questionnaire (VFQ-39) Peripheral Score(Assessed at Baseline, Week 160 (End of OLE Period))