Clinical trial NCT02693119: A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for Treatment of Leber's Hereditary Optic Neuropathy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leber's Hereditary Optic Neuropathy
Keywords: LHON
Ocuvia™
elamipretide
MTP-131
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Double Masked Period: Incidence of Ocular TEAEs
timeFrame: 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)
measure: Open Label Extension: Incidence of Ocular TEAEs
timeFrame: Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: Double Masked Period: Severity of Ocular TEAEs
timeFrame: 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)
measure: OLE: Severity of Ocular TEAEs
timeFrame: Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: Double Masked Period: Best Corrected Visual Acuity (BCVA)
timeFrame: 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)
measure: Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160 (follow-up visit).
Secondary outcomes:
measure: Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: PhNR-ERG B-wave Amplitude
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: PhNR Amplitude
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: PhNR Amplitude
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: PhNR/B-wave Amplitude Ratio
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted)
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked: VFQ-39 Composite
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Composite Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Open Label Extension Period: VFQ-39 General Health Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 General Vision Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 General Vision Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Ocular Pain Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Ocular Pain Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Near Activities Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Near Activities
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked Period: Mean Retinal Nerve Fiber (RNFL) Layer Thickness
timeFrame: Assessed at Baseline and Week 52 (end-of-treatment visit)
measure: Open Label Extension Period: Retinal Nerve Fiber Layer Thickness
timeFrame: Assessed at Baseline, Week 148
measure: Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.
measure: Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: Color Discrimination - Number of Plates
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit)
measure: Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit
timeFrame: Assessed at each visit from Baseline to Week 56 (follow-up visit)
measure: Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit
timeFrame: Assessed at each visit from Baseline from Week 68 to Week 160
measure: Double Masked Change From Baseline in Retinal Ganglion Cell Layer Thickness
timeFrame: Assessed at Baseline and Week 52 (end-of-treatment visit)
measure: Open Label Extension Period: Change From Baseline in Retinal Ganglion Cell Layer Thickness
timeFrame: Assessed at Baseline, Week 148,
measure: Double Masked: VFQ-39 Distance Activities Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Distance Activities Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Open Label Extension Period: VFQ-39 Social Functioning Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Social Functioning Score.
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Double Masked: VFQ-39 Mental Health Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Mental Health Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Role Difficulties Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Role Difficulties Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Open Label Extension Period:VFQ-39 Dependency Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Dependency Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Double Masked: VFQ-39 Color Vision Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: VFQ-39 Color Vision Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked: VFQ-39 Peripheral Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
measure: Open Label Extension Period: Visual Function Questionnaire (VFQ-39) Peripheral Score
timeFrame: Assessed at Baseline, Week 160 (End of OLE Period)
measure: Double Masked Period: Change in Intraocular Pressure (IOP)
timeFrame: 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)
measure: Open Label Extension Period: Intraocular Pressure (IOP)
timeFrame: Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: OLE: Slit Lamp Examination (SLE)-Vehicle Eye
timeFrame: Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: OLE: Slit Lamp Examination (SLE)-Elamipretide Eye
timeFrame: Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye
timeFrame: 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)
measure: Double Masked: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes
timeFrame: 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)
measure: Open Label Extension Period: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes
timeFrame: Assessed at Baseline, Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)
measure: Double Masked: VFQ-39 General Health Score
timeFrame: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Doheny Eye Center
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Alfredo Sadun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: