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

NCT02693119 | Completed Phase 2 Results

• 1 other identifier: SPILH-201
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Leber's Hereditary Optic Neuropathy

Keywords

LHON; Ocuvia™; elamipretide; MTP-131

Outcome Measures

Primary Outcomes (6)

• Double Masked Period: Incidence of Ocular TEAEs

  The incidence of ocular treatment emergent adverse events (TEAEs).

  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)

• Open Label Extension: Incidence of Ocular TEAEs

  Open Label Extension: The incidence of ocular treatment emergent adverse events (TEAEs).

  Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)

• Double Masked Period: Severity of Ocular TEAEs

  The severity of ocular treatment emergent adverse events (TEAEs).

  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: Severity of Ocular TEAEs

  The severity of ocular treatment emergent adverse events (TEAEs).

  Assessed at Week 68, 84, 100, 116, 132, 148, 152, Week 160/ (End of treatment visit)

• Double Masked Period: Best Corrected Visual Acuity (BCVA)

  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).

  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)

• Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale

  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).

  Assessed at each visit from Baseline from Week 68 to Week 160 (follow-up visit).

Secondary Outcomes (53)

• 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.

• 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.

• 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 Amplitude

  Assessed at each visit from Baseline to Week 56 (follow-up visit), except for Day 5 visit.

Study Arms (4)

Group 1

EXPERIMENTAL

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

Drug: elamipretide (MTP-131) 1% topical ophthalmic solution; Drug: Vehicle topical ophthalmic solution

Group 2

EXPERIMENTAL

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

Drug: elamipretide (MTP-131) 1% topical ophthalmic solution; Drug: Vehicle topical ophthalmic solution

Group 3

EXPERIMENTAL

One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).

Drug: elamipretide (MTP-131) 1% topical ophthalmic solution

OLE

EXPERIMENTAL

One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).

Drug: elamipretide (MTP-131) 1% topical ophthalmic solution

Interventions

elamipretide (MTP-131) 1% topical ophthalmic solution DRUG

Also known as: MTP-131, Bendavia

Group 1; Group 2; Group 3; OLE

Vehicle topical ophthalmic solution DRUG

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

Doheny Eye Center

Pasadena, California, 91105, United States

Location

MeSH Terms

Conditions

Optic Atrophy, Hereditary, Leber

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Results Point of Contact

• Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc

jim.carr@stealthbt.com

1-(617) 600-6888

Study Officials

• Alfredo Sadun, MD, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: February 26, 2016
• Study Start: March 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2019
• Last Updated: November 30, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-11

Locations

US (1)