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Phase 2 N=12 Randomized Quadruple-blind Treatment

A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for Treatment of Leber's Hereditary Optic Neuropathy

Leber's Hereditary Optic Neuropathy

Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Oct 2021
Primary outcome: Primary: Double Masked Period: Incidence of Ocular TEAEs — 3; 8; 1; 3 eyes

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
elamipretide (MTP-131) 1% topical ophthalmic solution (Drug); Vehicle topical ophthalmic solution (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
Stealth BioTherapeutics Inc.
Primary completion
Sep 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Double Masked Period: Incidence of Ocular TEAEs
3; 8; 1; 3; 0; 3
PRIMARY
Open Label Extension: Incidence of Ocular TEAEs
1; 1; 1; 1; 1; 1
PRIMARY
Double Masked Period: Severity of Ocular TEAEs
2; 0; 0; 1; 1; 0
PRIMARY
OLE: Severity of Ocular TEAEs
5; 0; 0; 6; 0; 0
PRIMARY
Double Masked Period: Best Corrected Visual Acuity (BCVA)
-3.1; -0.5; 0.3; 1.0; 2.0; 0.5
PRIMARY
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale
8.5; 6.00; 10.6; 5.4; 6.1; 6.1
SECONDARY
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude
0.0; 1.3; -0.2; 0.5; -3.5; -3.2
SECONDARY
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude
3.2; 4.0; -7.1; 1.8; 8.0; 4.9
SECONDARY
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude
-9.1; -4.5; -4.6; -3.4; 3.5; 14.6
SECONDARY
Open Label Extension Period: PhNR-ERG B-wave Amplitude
-15.4; -7.4; -6.0; -13.1; -28.7; -19.9
SECONDARY
Double Masked Period: PhNR Amplitude
-6.4; 0.3; -4.6; -3.3; -11.6; -0.7
SECONDARY
Open Label Extension Period: PhNR Amplitude
-7.1; 0.5; -2.5; -2.2; 3.3; 1.8
SECONDARY
Double Masked Period: PhNR/B-wave Amplitude Ratio
-0.102; -0.033; -0.036; -0.033; -0.113; 0.019
SECONDARY
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio
-0.097; -0.002; -0.021; -0.041; 0.012; -0.003
SECONDARY
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude
0.18; -0.21; -0.03; 1.08; 0.08; 0.00
SECONDARY
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude
-0.31; -0.70; 0.25; -0.09; -0.30; -0.13
SECONDARY
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline
-2.72; -4.80; 0.08; -0.08; 15.16; 15.38
SECONDARY
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted)
-8.36; -7.92; -3.50; -10.90; -32.02; -21.64
SECONDARY
Double Masked: VFQ-39 Composite
6.1; 5.7; 7.8
SECONDARY
Open Label Extension Period: VFQ-39 Composite Score
5.6; 13.9
SECONDARY
Open Label Extension Period: VFQ-39 General Health Score
-6.8; 6.7
SECONDARY
Double Masked: VFQ-39 General Vision Score
8.1; 1.3; 3.3
SECONDARY
Open Label Extension Period: VFQ-39 General Vision Score
9.3; 6.7
SECONDARY
Double Masked: VFQ-39 Ocular Pain Score
1.6; 3.1; 12.5
SECONDARY
Open Label Extension Period: VFQ-39 Ocular Pain Score
-16.1; -4.2
SECONDARY
Double Masked: VFQ-39 Near Activities Score
3.6; 9.2; 11.1
SECONDARY
Open Label Extension Period: VFQ-39 Near Activities
8.5; 16.7
SECONDARY
Double Masked Period: Mean Retinal Nerve Fiber (RNFL) Layer Thickness
-3.8; -2.6
SECONDARY
Open Label Extension Period: Retinal Nerve Fiber Layer Thickness
-1.0; 1.4
SECONDARY
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III
1.1; 2.1; 0.5; 1.6; 0.4; 0.9
SECONDARY
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline
3.3; 4.0; 5.1; 4.4; 3.1; 5.5
SECONDARY
Double Masked Period: Color Discrimination - Number of Plates
0.0; 0.1; 0.0; 0.1; 0.1; 0.3
SECONDARY
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit
1.3; 1.4; 1.9; 1.6; 2.8; 2.0
SECONDARY
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit
0.075; -0.019; 0.038; -0.028; 0.075; 0.047
SECONDARY
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit
0.225; 0.084; 0.300; 0.122; 0.281; 0.118
SECONDARY
Double Masked Change From Baseline in Retinal Ganglion Cell Layer Thickness
-1.5; -3.6
SECONDARY
Open Label Extension Period: Change From Baseline in Retinal Ganglion Cell Layer Thickness
-1.0; 3.4
SECONDARY
Double Masked: VFQ-39 Distance Activities Score
9.4; 0.0; 54.2
SECONDARY
Open Label Extension Period: VFQ-39 Distance Activities Score
12.5; 13.9
SECONDARY
Open Label Extension Period: VFQ-39 Social Functioning Score
8.3; 5.6
SECONDARY
Double Masked: VFQ-39 Social Functioning Score.
6.3; 0.0; 16.7
SECONDARY
Double Masked: VFQ-39 Mental Health Score
12.0; 19.7; 13.3
SECONDARY
Open Label Extension Period: VFQ-39 Mental Health Score
16.4; 29.2
SECONDARY
Double Masked: VFQ-39 Role Difficulties Score
4.7; 14.1; 10.4
SECONDARY
Open Label Extension Period: VFQ-39 Role Difficulties Score
8.0; 37.5
SECONDARY
Open Label Extension Period:VFQ-39 Dependency Score
16.1; 27.1
SECONDARY
Double Masked: VFQ-39 Dependency Score
9.4; -2.6; -8.3
SECONDARY
Double Masked: VFQ-39 Color Vision Score
6.3; 6.3; 0.0
SECONDARY
Open Label Extension Period: VFQ-39 Color Vision Score
-7.1; 8.3
SECONDARY
Double Masked: VFQ-39 Peripheral Score
0.0; 6.3; 66.7
SECONDARY
Open Label Extension Period: Visual Function Questionnaire (VFQ-39) Peripheral Score
0.0; 0.0
SECONDARY
Double Masked Period: Change in Intraocular Pressure (IOP)
-0.3; -0.2; 0.0; -0.4; -0.4; -0.5
SECONDARY
Open Label Extension Period: Intraocular Pressure (IOP)
-0.4; 0.8; 1.4; 0.4; -0.9; -0.2
SECONDARY
OLE: Slit Lamp Examination (SLE)-Vehicle Eye
0; 0; 0; 0; 0; 0
SECONDARY
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye
0; 0; 0; 0; 0; 0
SECONDARY
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye
1; 0; 1; 0; 1; 1
SECONDARY
Double Masked: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes
0; 0
SECONDARY
Open Label Extension Period: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes
0; 0
SECONDARY
Double Masked: VFQ-39 General Health Score
-3.8; -0.6; -5.8

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.

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02693119). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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