Trial Outcomes & Findings for A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for Treatment of Leber's Hereditary Optic Neuropathy (NCT NCT02693119)

NCT ID: NCT02693119

Last Updated: 2021-11-30

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome 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)
• Results posted on: 2021-11-30

Participant Flow

Participant milestones

Measure	Group 2 One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to a single eye and one drop of vehicle topical ophthalmic solution BID in the fellow eye	Group 3 One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).
Double-Blind Period STARTED	8	4
Double-Blind Period COMPLETED	8	4
Double-Blind Period NOT COMPLETED	0	0
Open-Label Period STARTED	8	4
Open-Label Period COMPLETED	8	3
Open-Label Period NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Group 2 One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to a single eye and one drop of vehicle topical ophthalmic solution BID in the fellow eye	Group 3 One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).
Open-Label Period Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Group 2 n=8 Participants One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to a single eye and one drop of vehicle topical ophthalmic solution BID in the fellow eye.	Group 3 n=4 Participants One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).	Total n=12 Participants Total of all reporting groups
Age, Continuous	35.4 years STANDARD_DEVIATION 14.47 • n=5 Participants	30.0 years STANDARD_DEVIATION 4.83 • n=7 Participants	33.6 years STANDARD_DEVIATION 12.11 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Elamipretide eye right eye only	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Elamipretide eye left eye only	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Elamipretide eye both eyes	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
BMI	25.70 kg/m^2 STANDARD_DEVIATION 3.937 • n=5 Participants	29.43 kg/m^2 STANDARD_DEVIATION 2.081 • n=7 Participants	26.94 kg/m^2 STANDARD_DEVIATION 3.796 • n=5 Participants

PRIMARY outcome

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)

Population: All participants for whom ocular AEs were measured.

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

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Incidence of Ocular TEAEs Nervous system disorders: Parosmia	0 eyes	2 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Conjunctival hyperaemia	3 eyes	8 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Punctate keratitis	1 eyes	3 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Dry eye	0 eyes	3 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Eye irritation	1 eyes	2 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Eyelid irritation	1 eyes	2 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Eyelid exfoliation	1 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Lacrimation increased	0 eyes	2 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Choroidal neovascularisation	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Conjunctival oedema	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Eyelid oedema	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Noninfective conjunctivitis	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Immune system disorders: Hypersensitivity	1 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Infections and infestations Conjunctivitis	1 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Injury, poisoning and procedural complications: Foreign body in eye	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Injury, poisoning and procedural complications: Skin abrasion	0 eyes	1 eyes	—	—	—	—
Double Masked Period: Incidence of Ocular TEAEs Investigations: Intraocular pressure increased	1 eyes	1 eyes	—	—	—	—

PRIMARY outcome

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

Population: All participants for whom ocular AEs were measured. For the ocular AE Injury, poisoning and procedural complications: Fall, the subject fell and had a black eye. For ocular AE Immune system disorders Seasonal allergy, individual reported seasonal allergies affecting vision in both eyes. For General disorders and administration site conditions Application site pain, individuals reported burning in eyes, worsening of vision upon application of vehicle or elamipretide eyes.

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

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension: Incidence of Ocular TEAEs Injury, poisoning and procedural complications: Fall (resulting in black eye)	0 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Cataract nuclear	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Ocular hyperaemia	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Dry eye	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Eye irritation	2 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Eyelid irritation	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Visual acuity reduced	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Visual impairment	0 eyes	2 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Eye disorders Punctate keratitis	1 eyes	0 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs General disorders and administration site conditions Application site pain (eyes burn, vision worse)	3 eyes	5 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Immune system disorders Seasonal allergy (worsening vision in eyes)	1 eyes	1 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Injury, poisoning and procedural complications: Corneal abrasian	1 eyes	0 eyes	—	—	—	—
Open Label Extension: Incidence of Ocular TEAEs Injury, poisoning and procedural complications: Eye contusion	0 eyes	1 eyes	—	—	—	—

PRIMARY outcome

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)

Population: All participants for whom ocular AEs were measured.

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

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe n=8 eyes 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Severity of Ocular TEAEs Conjunctival hyperaemia	2 eyes	0 eyes	0 eyes	1 eyes	1 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Dry eye	0 eyes	0 eyes	0 eyes	3 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Eye irritation	1 eyes	0 eyes	0 eyes	2 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Punctate keratitis	1 eyes	0 eyes	0 eyes	3 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Eyelid irritation	1 eyes	0 eyes	0 eyes	2 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Eyelid exfoliation	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Lacrimation increased	0 eyes	0 eyes	0 eyes	2 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Choroidal neovascularisation	2 eyes	0 eyes	0 eyes	0 eyes	0 eyes	1 eyes
Double Masked Period: Severity of Ocular TEAEs Conjunctival oedema	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Eyelid oedema	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Noninfective conjunctivitis	0 eyes	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Immune system disorders: Hypersensitivity	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Infections and infestations Conjunctivitis	0 eyes	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Injury, poisoning and procedural complications: Foreign body in eye	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Injury, poisoning and procedural complications: Skin abrasion	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Investigations: Intraocular pressure increased	0 eyes	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes
Double Masked Period: Severity of Ocular TEAEs Nervous system disorders: Parosmia	0 eyes	0 eyes	0 eyes	2 eyes	0 eyes	0 eyes

PRIMARY outcome

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

Population: All participants for whom ocular AEs were measured.

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

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe n=8 eyes 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe n=16 eyes 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
OLE: Severity of Ocular TEAEs Visual impairment	0 eyes	0 eyes	0 eyes	2 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Injury, poisoning and procedural complications Corneal abrasian	1 eyes	0 eyes	0 eyes	0 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Eye disorders Cataract nuclear	5 eyes	0 eyes	0 eyes	6 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Punctate keratitis	1 eyes	0 eyes	0 eyes	0 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Dry eye	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Eye irritation	2 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Eyelid irritation	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Ocular hyperaemia	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Visual acuity reduced	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs General disorders and administration site conditions Application site pain	3 eyes	0 eyes	0 eyes	5 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Immune system disorders Seasonal allergy	1 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Injury, poisoning and procedural complications Eye contusion	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes
OLE: Severity of Ocular TEAEs Injury, poisoning and procedural complications: Fall	0 eyes	0 eyes	0 eyes	1 eyes	0 eyes	0 eyes

PRIMARY outcome

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)

Population: All participants for whom BCVA was measured.

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).

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 36	6.6 letters Standard Deviation 11.73	1.9 letters Standard Deviation 4.53	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Day 5	-3.1 letters Standard Deviation 9.34	-0.5 letters Standard Deviation 4.50	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 4	0.3 letters Standard Deviation 3.33	1.0 letters Standard Deviation 3.54	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 8	2.0 letters Standard Deviation 3.02	0.5 letters Standard Deviation 5.29	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 12	2.8 letters Standard Deviation 5.15	0.4 letters Standard Deviation 6.47	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 16	3.0 letters Standard Deviation 3.38	0.6 letters Standard Deviation 4.06	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 20	4.0 letters Standard Deviation 10.42	1.7 letters Standard Deviation 4.63	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 24	4.1 letters Standard Deviation 9.98	2.1 letters Standard Deviation 3.79	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 28	5.5 letters Standard Deviation 11.99	1.4 letters Standard Deviation 4.99	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 32	4.8 letters Standard Deviation 15.54	2.7 letters Standard Deviation 7.67	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 40	2.6 letters Standard Deviation 11.56	3.2 letters Standard Deviation 4.40	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 44	6.1 letters Standard Deviation 11.85	3.5 letters Standard Deviation 5.97	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 48	5.1 letters Standard Deviation 16.58	4.8 letters Standard Deviation 4.89	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 52	4.6 letters Standard Deviation 16.27	2.9 letters Standard Deviation 5.45	—	—	—	—
Double Masked Period: Best Corrected Visual Acuity (BCVA) Week 56 (follow up Visit)	1.7 letters Standard Deviation 2.89	5.3 letters Standard Deviation 4.16	—	—	—	—

PRIMARY outcome

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

Population: All participants for whom BCVA was measured.

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).

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 104	-3.5 letters Standard Deviation 6.36	2.5 letters Standard Deviation 0.71	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 132	11.6 letters Standard Deviation 17.04	4.3 letters Standard Deviation 8.36	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 148	2.8 letters Standard Deviation 2.50	2.9 letters Standard Deviation 4.05	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 68	8.5 letters Standard Deviation 14.16	6.00 letters Standard Deviation 7.18	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 84	10.6 letters Standard Deviation 18.66	5.4 letters Standard Deviation 7.70	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 100	6.1 letters Standard Deviation 13.86	6.1 letters Standard Deviation 6.12	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 116	11.3 letters Standard Deviation 14.00	5.9 letters Standard Deviation 6.71	—	—	—	—
Open Label Extension Period: Best Corrected Visual Acuity (BCVA) Using the Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale Week 160	1.7 letters Standard Deviation 2.08	7.7 letters Standard Deviation 4.16	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom photopic negative response electroretinography PhNR-ERG was measured.

Change from baseline in photopic negative response electroretinography (PhNR-ERG) a-wave amplitude by Visit. Photopic negative response electroretinography (PhNR-ERG) assesses retinal cell function. A decrease in the amplitude of the a-wave is associated with worse outcomes. Change from baseline in a-wave amplitude: a more positive number equals a decrease in amplitude, and therefore a worse outcome, a more negative number mean a better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 16	1.1 µV Standard Deviation 6.71	0.7 µV Standard Deviation 6.30	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 20	1.5 µV Standard Deviation 4.64	1.1 µV Standard Deviation 4.71	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 40	2.2 µV Standard Deviation 10.07	1.5 µV Standard Deviation 6.28	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 48	3.4 µV Standard Deviation 8.31	2.9 µV Standard Deviation 6.19	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 4	0.0 µV Standard Deviation 6.61	1.3 µV Standard Deviation 6.81	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 8	-0.2 µV Standard Deviation 6.92	0.5 µV Standard Deviation 7.50	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 12	-3.5 µV Standard Deviation 11.09	-3.2 µV Standard Deviation 10.18	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 24	2.0 µV Standard Deviation 6.18	2.0 µV Standard Deviation 6.56	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 28	0.4 µV Standard Deviation 5.11	2.5 µV Standard Deviation 5.80	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 32	2.0 µV Standard Deviation 8.18	0.3 µV Standard Deviation 5.64	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 36	-2.5 µV Standard Deviation 11.62	0.2 µV Standard Deviation 7.00	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 44	1.0 µV Standard Deviation 11.05	3.2 µV Standard Deviation 6.55	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 52	2.3 µV Standard Deviation 5.58	2.0 µV Standard Deviation 5.16	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 56 (Follow up Visit)	7.0 µV Standard Deviation 2.93	5.1 µV Standard Deviation 8.71	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom photopic negative response electroretinography (PhNR-ERG) was measured.

Change from baseline in photopic negative response electroretinography (PhNR-ERG) a-wave Amplitude by Visit. Photopic negative response electroretinography (PhNR-ERG) assesses retinal cell function. A decrease in the amplitude of the a-wave is associated with worse outcomes. Change from baseline in a-wave amplitude: a more positive number equals a decrease in amplitude, and therefore a worse outcome, a more negative number mean a better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 132	5.7 µV Standard Deviation 7.07	1.4 µV Standard Deviation 3.99	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 68	3.2 µV Standard Deviation 9.24	4.0 µV Standard Deviation 6.00	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 84	-7.1 µV Standard Deviation 19.27	1.8 µV Standard Deviation 6.81	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 100	8.0 µV Standard Deviation 5.69	4.9 µV Standard Deviation 4.41	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 104	5.3 µV Standard Deviation 3.27	3.0 µV Standard Deviation 1.71	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 116	-2.7 µV Standard Deviation 9.39	0.3 µV Standard Deviation 5.93	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 148	5.4 µV Standard Deviation 8.92	1.5 µV Standard Deviation 3.84	—	—	—	—
Open Label Extension Period: Photopic Negative Response Electroretinography (PhNR-ERG) A-wave Amplitude Week 160	2.9 µV Standard Deviation 2.82	2.82 µV Standard Deviation 7.60	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom PhNR-ERG was measured.

Change from baseline in photopic negative response electroretinography (PhNR-ERG) b-wave amplitude by visit. Photopic negative response electroretinography (PhNR -ERG) assesses retinal cell function. A decrease in the amplitude of the b-wave is associated with worse outcomes. Change from baseline in b-wave amplitude: a more negative number equals a decrease in amplitude, and therefore a worse outcome, a more positive number mean a better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 36	2.4 µV Standard Deviation 29.87	2.2 µV Standard Deviation 22.06	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 20	-2.2 µV Standard Deviation 22.48	-6.4 µV Standard Deviation 29.35	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 4	-9.1 µV Standard Deviation 14.36	-4.5 µV Standard Deviation 31.48	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 8	-4.6 µV Standard Deviation 21.82	-3.4 µV Standard Deviation 22.33	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 12	3.5 µV Standard Deviation 17.85	14.6 µV Standard Deviation 27.23	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 16	-2.8 µV Standard Deviation 28.02	-2.6 µV Standard Deviation 19.83	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 24	-8.9 µV Standard Deviation 20.58	-1.0 µV Standard Deviation 28.06	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 28	-0.7 µV Standard Deviation 19.04	-11.6 µV Standard Deviation 17.75	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 32	-5.6 µV Standard Deviation 13.57	1.8 µV Standard Deviation 24.58	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 40	-0.1 µV Standard Deviation 23.58	-8.1 µV Standard Deviation 23.17	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 44	1.9 µV Standard Deviation 21.35	-5.0 µV Standard Deviation 21.01	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 48	-6.9 µV Standard Deviation 24.08	-10.5 µV Standard Deviation 23.80	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 52	-1.3 µV Standard Deviation 13.97	-5.4 µV Standard Deviation 18.99	—	—	—	—
Double Masked Period: Photopic Negative Response Electroretinography (PhNR-ERG) B-wave Amplitude Week 56 (Follow up)	-18.4 µV Standard Deviation 28.05	-17.5 µV Standard Deviation 49.57	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom PhNR-ERG was measured.

Change from baseline in photopic negative response electroretinography (PhNR-ERG) b-wave Amplitude by Visit. Photopic negative response electroretinography (PhNR -ERG) assesses retinal cell function. A decrease in the amplitude of the b-wave is associated with worse outcomes. Change from baseline in b-wave amplitude: a more negative number equals a decrease in amplitude, and therefore a worse outcome, a more positive number means a better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 68	-15.4 µV Standard Deviation 25.98	-7.4 µV Standard Deviation 17.10	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 84	-6.0 µV Standard Deviation 23.97	-13.1 µV Standard Deviation 20.97	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 100	-28.7 µV Standard Deviation 23.23	-19.9 µV Standard Deviation 18.04	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 104	-17.7 µV Standard Deviation 5.23	-14.2 µV Standard Deviation 4.62	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 116	17.1 µV Standard Deviation 44.40	4.9 µV Standard Deviation 18.79	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 132	-17.1 µV Standard Deviation 17.08	-1.3 µV Standard Deviation 18.81	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 148	-13.1 µV Standard Deviation 30.88	-7.3 µV Standard Deviation 18.84	—	—	—	—
Open Label Extension Period: PhNR-ERG B-wave Amplitude Week 160	-17.8 µV Standard Deviation 14.15	-38.1 µV Standard Deviation 25.20	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom PhNR Amplitude was measured.

Double Masked Period: Change from baseline in PhNR Amplitude by Visit. Photopic negative response electroretinography (PhNR -ERG) assesses retinal cell function. A decrease in PhNR amplitude means worse outcome. Change from baseline: A more negative number means a better outcome, a more positive number means a worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: PhNR Amplitude Week 8	-4.6 µV Standard Deviation 26.80	-3.3 µV Standard Deviation 27.28	—	—	—	—
Double Masked Period: PhNR Amplitude Week 12	-11.6 µV Standard Deviation 26.59	-0.7 µV Standard Deviation 14.90	—	—	—	—
Double Masked Period: PhNR Amplitude Week 16	-4.5 µV Standard Deviation 10.26	-3.1 µV Standard Deviation 17.35	—	—	—	—
Double Masked Period: PhNR Amplitude Week 4	-6.4 µV Standard Deviation 22.27	0.3 µV Standard Deviation 22.05	—	—	—	—
Double Masked Period: PhNR Amplitude Week 20	0.5 µV Standard Deviation 20.65	-3.1 µV Standard Deviation 19.58	—	—	—	—
Double Masked Period: PhNR Amplitude Week 24	-4.3 µV Standard Deviation 21.51	-0.5 µV Standard Deviation 16.15	—	—	—	—
Double Masked Period: PhNR Amplitude Week 28	-7.1 µV Standard Deviation 26.32	-1.5 µV Standard Deviation 13.92	—	—	—	—
Double Masked Period: PhNR Amplitude Week 32	-4.1 µV Standard Deviation 25.11	-3.1 µV Standard Deviation 13.61	—	—	—	—
Double Masked Period: PhNR Amplitude Week 36	-8.5 µV Standard Deviation 24.94	-3.4 µV Standard Deviation 10.17	—	—	—	—
Double Masked Period: PhNR Amplitude Week 40	-2.3 µV Standard Deviation 23.16	-4.4 µV Standard Deviation 10.92	—	—	—	—
Double Masked Period: PhNR Amplitude Week 44	-9.8 µV Standard Deviation 29.75	-1.5 µV Standard Deviation 11.91	—	—	—	—
Double Masked Period: PhNR Amplitude Week 48	-2.8 µV Standard Deviation 22.76	-3.7 µV Standard Deviation 13.14	—	—	—	—
Double Masked Period: PhNR Amplitude Week 52	-4.0 µV Standard Deviation 25.41	-3.3 µV Standard Deviation 11.73	—	—	—	—
Double Masked Period: PhNR Amplitude Week 56 (Follow up)	-1.6 µV Standard Deviation 16.71	-5.7 µV Standard Deviation 6.45	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom PhNR Amplitude was measured.

Open Label Extension Period: Change from baseline in PhNR Amplitude by Visit. Photopic negative response electroretinography (PhNR -ERG) assesses retinal cell function. A decrease in PhNR amplitude means worse outcome. Change from baseline: A more negative number means a better outcome, a more positive number means a worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: PhNR Amplitude Week 68	-7.1 µV Standard Deviation 22.91	0.5 µV Standard Deviation 16.60	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 84	-2.5 µV Standard Deviation 25.45	-2.2 µV Standard Deviation 11.96	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 100	3.3 µV Standard Deviation 16.25	1.8 µV Standard Deviation 6.50	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 104	3.3 µV Standard Deviation 1.03	-1.2 µV Standard Deviation 6.72	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 116	-5.1 µV Standard Deviation 20.89	0.4 µV Standard Deviation 9.00	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 132	-3.6 µV Standard Deviation 20.98	0.5 µV Standard Deviation 10.75	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 148	-4.1 µV Standard Deviation 8.75	-1.4 µV Standard Deviation 4.23	—	—	—	—
Open Label Extension Period: PhNR Amplitude Week 160	-9.9 µV Standard Deviation 4.31	-10.0 µV Standard Deviation 11.64	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom PhNR was measured.

Double Masked Period: Change from baseline in PhNR/b-wave amplitude ratio by Visit. Photopic negative response electroretinography (PhNR assesses retinal cell function. A decrease in PhNR amplitude means worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 4	-0.102 ratio Standard Deviation 0.2225	-0.033 ratio Standard Deviation 0.2793	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 8	-0.036 ratio Standard Deviation 0.3101	-0.033 ratio Standard Deviation 0.3385	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 12	-0.113 ratio Standard Deviation 0.2415	0.019 ratio Standard Deviation 0.1721	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 16	-0.059 ratio Standard Deviation 0.1179	-0.070 ratio Standard Deviation 0.2285	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 20	-0.018 ratio Standard Deviation 0.2005	-0.066 ratio Standard Deviation 0.2365	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 24	-0.052 ratio Standard Deviation 0.2080	0.014 ratio Standard Deviation 0.2131	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 28	-0.044 ratio Standard Deviation 0.2281	-0.024 ratio Standard Deviation 0.1634	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 32	-0.033 ratio Standard Deviation 0.2414	-0.031 ratio Standard Deviation 0.1513	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 36	-0.104 ratio Standard Deviation 0.2479	-0.013 ratio Standard Deviation 0.1795	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 40	-0.007 ratio Standard Deviation 0.2190	-0.046 ratio Standard Deviation 0.1202	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 44	-0.138 ratio Standard Deviation 0.3194	0.013 ratio Standard Deviation 0.2206	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 48	-0.020 ratio Standard Deviation 0.2366	-0.059 ratio Standard Deviation 0.1533	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 52	-0.044 ratio Standard Deviation 0.2428	-0.029 ratio Standard Deviation 0.1299	—	—	—	—
Double Masked Period: PhNR/B-wave Amplitude Ratio Week 56 (Follow up)	0.009 ratio Standard Deviation 0.2670	-0.063 ratio Standard Deviation 0.1149	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom PhNR-ERG was measured.

Open Label Extension Period: Change from baseline by visit PhNR/b Wave Amplitude Ratio by visit. A reduced amplitude ratio equals worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 68	-0.097 Ratio Standard Deviation 0.2453	-0.002 Ratio Standard Deviation 0.1722	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 84	-0.021 Ratio Standard Deviation 0.2678	-0.041 Ratio Standard Deviation 0.1207	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 100	0.012 Ratio Standard Deviation 0.1523	-0.003 Ratio Standard Deviation 0.0796	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 104	0.019 Ratio Standard Deviation 0.0066	-0.048 Ratio Standard Deviation 0.0667	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 116	-0.034 Ratio Standard Deviation 0.2112	0.000 Ratio Standard Deviation 0.0971	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 132	-0.055 Ratio Standard Deviation 0.1957	0.032 Ratio Standard Deviation 0.2010	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 148	-0.035 Ratio Standard Deviation 0.0717	-0.046 Ratio Standard Deviation 0.0982	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR/b Wave Amplitude Ratio Week 160	-0.155 Ratio Standard Deviation 0.1075	-0.212 Ratio Standard Deviation 0.2211	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom PhNR-ERG was measured.

Double Masked Period: Change from baseline by visit in PhNR Peak to Trough Adjusted for a-wave Amplitude by Visit. Calculated as (b-wave amplitude - PhNR amplitude)/a-wave amplitude. A reduced amplitude ratio equals worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 4	0.18 Ratio Standard Deviation 0.392	-0.21 Ratio Standard Deviation 1.100	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 8	-0.03 Ratio Standard Deviation 0.655	1.08 Ratio Standard Deviation 4.628	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 12	0.08 Ratio Standard Deviation 0.827	0.00 Ratio Standard Deviation 0.962	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 16	-0.53 Ratio Standard Deviation 1.260	-0.01 Ratio Standard Deviation 0.862	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 20	-0.32 Ratio Standard Deviation 0.992	0.10 Ratio Standard Deviation 1.022	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 24	-0.35 Ratio Standard Deviation 0.856	-0.29 Ratio Standard Deviation 0.746	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 28	-0.35 Ratio Standard Deviation 0.819	-0.21 Ratio Standard Deviation 1.358	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 32	-0.24 Ratio Standard Deviation 0.820	-0.15 Ratio Standard Deviation 0.606	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 36	-0.05 Ratio Standard Deviation 0.687	-0.70 Ratio Standard Deviation 1.162	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 40	0.63 Ratio Standard Deviation 0.546	0.02 Ratio Standard Deviation 1.123	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 44	-0.68 Ratio Standard Deviation 0.438	-0.66 Ratio Standard Deviation 1.016	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 48	-0.61 Ratio Standard Deviation 0.811	-0.31 Ratio Standard Deviation 0.769	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 52	-0.61 Ratio Standard Deviation 0.291	-0.37 Ratio Standard Deviation 0.403	—	—	—	—
Double Masked Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 56 (Follow up)	-1.22 Ratio Standard Deviation 0.114	-0.87 Ratio Standard Deviation 0.274	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom PhNR-ERG was measured.

Open Label Extension Period: Change from baseline by visit in PhNR Peak to Trough Adjusted for a-wave Amplitude by Visit. [Calculated by b-wave amplitude - PhNR amplitude)/a-wave amplitude.] Photopic negative response electroretinography (PhNR-ERG) assesses retinal cell function. A decrease in the amplitude of the a-wave is associated with worse outcomes. A reduced amplitude ratio equals worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 132	-0.77 Ratio Standard Deviation 0.831	-0.38 Ratio Standard Deviation 0.329	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 68	-0.31 Ratio Standard Deviation 1.006	-0.70 Ratio Standard Deviation 0.859	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 84	0.25 Ratio Standard Deviation 1.700	-0.09 Ratio Standard Deviation 1.050	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 100	-0.30 Ratio Standard Deviation 0.591	-0.13 Ratio Standard Deviation 0.407	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 104	-0.10 Ratio Standard Deviation 0.454	-0.09 Ratio Standard Deviation 0.103	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 116	-0.64 Ratio Standard Deviation 1.189	-0.46 Ratio Standard Deviation 0.673	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 148	-0.91 Ratio Standard Deviation 0.609	-0.16 Ratio Standard Deviation 0.437	—	—	—	—
Open Label Extension Period: Change From Baseline by Visit PhNR Peak to Trough Adjusted for A-wave Amplitude Week 160	-0.46 Ratio Standard Deviation 0.457	-0.92 Ratio Standard Deviation 1.027	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom PhNR-ERG was measured.

Double Masked Period: Change from baseline in PhNR Peak to Trough Amplitude (Unadjusted) by Visit. Calculated as b-wave amplitude - PhNR amplitude. Photopic negative response electroretinography (PhNR-ERG) assesses retinal cell function. A decrease in amplitude is associated with worse outcomes.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 4	-2.72 µV Standard Deviation 24.750	-4.80 µV Standard Deviation 31.025	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 8	0.08 µV Standard Deviation 18.496	-0.08 µV Standard Deviation 31.421	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 12	15.16 µV Standard Deviation 38.016	15.38 µV Standard Deviation 33.898	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 16	1.70 µV Standard Deviation 32.016	0.52 µV Standard Deviation 25.629	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 20	-2.62 µV Standard Deviation 20.398	-3.29 µV Standard Deviation 21.498	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 24	-4.57 µV Standard Deviation 25.171	-0.54 µV Standard Deviation 30.470	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 28	6.38 µV Standard Deviation 26.095	-10.18 µV Standard Deviation 19.504	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 32	-1.42 µV Standard Deviation 28.294	4.86 µV Standard Deviation 26.750	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 36	10.94 µV Standard Deviation 48.051	5.57 µV Standard Deviation 26.427	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 40	2.22 µV Standard Deviation 43.149	-3.74 µV Standard Deviation 27.206	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 44	11.74 µV Standard Deviation 46.933	-3.46 µV Standard Deviation 26.042	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 48	-4.12 µV Standard Deviation 34.581	-6.86 µV Standard Deviation 28.849	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 52	2.73 µV Standard Deviation 19.124	-2.15 µV Standard Deviation 22.109	—	—	—	—
Double Masked Period: PhNR Peak to Trough Amplitude (Unadjusted) From Baseline Week 56 (Follow up)	-16.78 µV Standard Deviation 19.472	-11.80 µV Standard Deviation 49.865	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom PhNR-ERG was measured.

Open Label Extension Period: Change from baseline in PhNR Peak to Trough Amplitude (Unadjusted) by Visit. b-wave amplitude - PhNR amplitude. Photopic negative response electroretinography (PhNR-ERG) assesses retinal cell function. A decrease in the amplitude of the a-wave is associated with worse outcomes.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 68	-8.36 µV Standard Deviation 36.178	-7.92 µV Standard Deviation 21.402	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 84	-3.50 µV Standard Deviation 13.206	-10.90 µV Standard Deviation 22.928	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 100	-32.02 µV Standard Deviation 23.994	-21.64 µV Standard Deviation 21.432	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 104	-21.01 µV Standard Deviation 4.193	-13.01 µV Standard Deviation 11.340	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 116	22.26 µV Standard Deviation 42.352	4.52 µV Standard Deviation 22.231	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 132	-13.56 µV Standard Deviation 27.012	-1.85 µV Standard Deviation 15.341	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 148	-8.99 µV Standard Deviation 35.662	-5.84 µV Standard Deviation 19.242	—	—	—	—
Open Label Extension Period: PhNR Peak to Trough Amplitude (Unadjusted) Week 160	-7.87 µV Standard Deviation 11.415	-28.17 µV Standard Deviation 31.249	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 was measured.

Double Masked: Change from baseline in Visual Function Questionnaire (VFQ-39) Composite score by visit. National Eye Institute VFQ-39 measures health-related quality of life in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, peripheral vision, and composite score. For each domain: the lowest and highest possible scores are 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 Participants Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=4 Participants Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Composite Week 52	6.1 score on a scale Standard Deviation 5.63	5.7 score on a scale Standard Deviation 8.07	—	—	—	—
Double Masked: VFQ-39 Composite Week 56 (Follow-up Visit)	7.8 score on a scale Standard Deviation 7.02	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom change in VFQ-39 composite score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Composite score.National Eye Institute VFQ-39 measures health-related quality of life in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, peripheral vision, and composite score. For each domain: the lowest and highest possible scores are 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Composite Score	5.6 score on a scale Standard Deviation 11.30	13.9 score on a scale Standard Deviation 8.66	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change from baseline in Visual Function Questionnaire (VFQ-39) General Health score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) General Health score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 General Health Score	-6.8 score on a scale Standard Deviation 10.58	6.7 score on a scale Standard Deviation 11.55	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom change from VFQ-39 General Health score was measured.

Change from baseline in VFQ-39 General Vision Score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculate

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 General Vision Score Week 56 (Follow-up Visit)	3.3 score on a scale Standard Deviation 7.64	—	—	—	—	—
Double Masked: VFQ-39 General Vision Score Week 52	8.1 score on a scale Standard Deviation 8.84	1.3 score on a scale Standard Deviation 11.09	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) General Vision was measured.

Change from baseline in VFQ-39 General Vision score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculate

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 General Vision Score	9.3 score on a scale Standard Deviation 13.36	6.7 score on a scale Standard Deviation 11.55	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom change from VFQ-39 General Health score was measured.

Change from baseline in VFQ-39 Ocular Pain score. National Eye Institute VFQ-39 measures health-related quality of life in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, peripheral vision, and composite score. For each domain: the lowest and highest possible scores are 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Ocular Pain Score Week 52	1.6 score on a scale Standard Deviation 12.39	3.1 score on a scale Standard Deviation 6.25	—	—	—	—
Double Masked: VFQ-39 Ocular Pain Score Week 56 (Follow-up Visit)	12.5 score on a scale Standard Deviation 12.50	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Ocular Pain was measured.

Change from baseline in VFQ-39 Ocular Pain score by visit. National Eye Institute VFQ-39 measures health-related quality of life in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, peripheral vision, and composite score. For each domain: the lowest and highest possible scores are 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Ocular Pain Score	-16.1 score on a scale Standard Deviation 20.04	-4.2 score on a scale Standard Deviation 7.22	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom change from VFQ-39 Near Activities score was measured.

Change from Baseline in VFQ-39 Near Activities Score from Baseline. National Eye Institute VFQ-39 measures health-related quality of life in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, peripheral vision, and composite score. For each domain: the lowest and highest possible scores are 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Near Activities Score Week 52	3.6 score on a scale Standard Deviation 7.53	9.2 score on a scale Standard Deviation 9.41	—	—	—	—
Double Masked: VFQ-39 Near Activities Score Week 56 (Follow-up Visit)	11.1 score on a scale Standard Deviation 9.62	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom change in VFQ-39 Near Activities score was measured.

Change from Baseline in Visual Function Questionnaire (VFQ-39) Near Activities score.. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; score ranges from 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Near Activities	8.5 score on a scale Standard Deviation 11.03	16.7 score on a scale Standard Deviation 16.67	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline and Week 52 (end-of-treatment visit)

Population: All participants for whom Retinal Nerve Fiber Layer Thickness was measured.

Change from baseline in retinal nerve fiber layer thickness by spectral domain optical coherence tomography (SD-OCT). RNFL measures the loss of retinal ganglion cell axons. RNFL thickness decreases as disease progresses. A positive number, or, absence of change from baseline reflects a good clinical outcome, a negative number reflects loss of thickness, or a bad outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Mean Retinal Nerve Fiber (RNFL) Layer Thickness	-3.8 µm Standard Deviation 7.52	-2.6 µm Standard Deviation 4.76	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 148

Population: All participants for whom Change in Retinal Nerve Fiber Layer Thickness by SD-OCT was measured.

Open Label Extension Period: Change from baseline in Retinal Nerve Fiber Layer Thickness by SD-OCT by visit. Change from baseline in retinal nerve fiber layer thickness by spectral domain optical coherence tomography (SD-OCT). RNFL measures the loss of retinal ganglion cell axons. RNFL thickness decreases as disease progresses. A positive number, or, absence of change from baseline reflects a good clinical outcome, a negative number reflects loss of thickness, or a bad outcome.

Outcome measures

Measure	Single Eye in DM Period n=1 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=3 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Retinal Nerve Fiber Layer Thickness	-1.0 µm	1.4 µm Standard Deviation 2.70	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III was measured

Change from Baseline in visual field Mean Deviation(MD) as measured by Humphrey automated visual field testing stimulus III by visit. The Humphrey visual field test measures the entire area of peripheral vision that can be seen while the eye is focused on a central point. Mean deviation (MD) is the mean deviation in the patient's results compared to those expected from the age-matched normative database. Lower/More negative scores mean worse outcome, higher/more positive score means better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 4	1.1 dB Standard Deviation 3.62	2.1 dB Standard Deviation 3.94	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 8	0.5 dB Standard Deviation 3.88	1.6 dB Standard Deviation 3.82	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 12	0.4 dB Standard Deviation 3.85	0.9 dB Standard Deviation 3.42	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 16	0.3 dB Standard Deviation 1.87	1.9 dB Standard Deviation 2.62	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 20	-0.4 dB Standard Deviation 5.31	2.1 dB Standard Deviation 4.23	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 24	2.0 dB Standard Deviation 3.33	1.1 dB Standard Deviation 2.74	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 28	1.7 dB Standard Deviation 4.40	1.3 dB Standard Deviation 4.86	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 32	2.9 dB Standard Deviation 4.27	1.4 dB Standard Deviation 4.38	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 36	2.6 dB Standard Deviation 4.75	2.2 dB Standard Deviation 3.55	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 40	2.8 dB Standard Deviation 5.98	2.2 dB Standard Deviation 3.55	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 44	1.8 dB Standard Deviation 6.03	2.8 dB Standard Deviation 5.10	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 48	1.5 dB Standard Deviation 3.66	1.4 dB Standard Deviation 3.92	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 52	0.9 dB Standard Deviation 4.18	2.2 dB Standard Deviation 3.30	—	—	—	—
Double Masked Period: Visual Field Mean Deviation as Measured by Humphrey Automated Visual Field Testing Stimulus III Week 56 (Follow up)	3.7 dB Standard Deviation 5.67	1.6 dB Standard Deviation 3.53	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom Visual Field Mean Deviation (dB) measured by Humphrey from Baseline was measured.

Change from Baseline in visual field Mean Deviation(MD) as measured by Humphrey automated visual field testing stimulus III by visit. The Humphrey visual field test measures the entire area of peripheral vision that can be seen while the eye is focused on a central point. Mean deviation (MD) is the mean deviation in the patient's results compared to those expected from the age-matched normative database. Lower/More negative scores mean worse outcome, higher/more positive score means better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 84	5.1 dB Standard Deviation 6.66	4.4 dB Standard Deviation 6.53	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 100	3.1 dB Standard Deviation 6.85	5.5 dB Standard Deviation 8.04	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 104	0.9 dB Standard Deviation 0.97	2.9 dB Standard Deviation 0.99	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 116	4.4 dB Standard Deviation 5.48	4.7 dB Standard Deviation 6.21	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 132	4.7 dB Standard Deviation 8.43	4.0 dB Standard Deviation 6.62	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 148	5.5 dB Standard Deviation 8.16	5.6 dB Standard Deviation 9.51	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 160	6.3 dB Standard Deviation 13.67	11.5 dB Standard Deviation 16.98	—	—	—	—
Open Label Extension Period: Visual Field Mean Deviation (dB) Measured by Humphrey From Baseline Week 68	3.3 dB Standard Deviation 5.59	4.0 dB Standard Deviation 6.66	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline to Week 56 (follow-up visit)

Population: All participants for whom Number of Plates was measured

Double Masked Period: Change from Baseline in Color Discrimination - Number of Plates from Baseline by Visit by Ishihara Test. Score range: 0-38. Higher number equals better color discrimination equals better outcome. Lower number equals worse color discrimination equals worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Color Discrimination - Number of Plates Week 20	0.5 Plates Standard Deviation 0.93	0.3 Plates Standard Deviation 0.60	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 24	0.3 Plates Standard Deviation 0.71	0.5 Plates Standard Deviation 0.97	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Day 5	0.0 Plates Standard Deviation 0.00	0.1 Plates Standard Deviation 0.57	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 4	0.0 Plates Standard Deviation 0.00	0.1 Plates Standard Deviation 0.50	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 8	0.1 Plates Standard Deviation 0.35	0.3 Plates Standard Deviation 0.58	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 12	0.3 Plates Standard Deviation 0.71	0.2 Plates Standard Deviation 0.75	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 16	0.0 Plates Standard Deviation 0.00	0.4 Plates Standard Deviation 0.89	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 28	0.9 Plates Standard Deviation 1.36	0.8 Plates Standard Deviation 1.39	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 32	0.8 Plates Standard Deviation 1.16	0.7 Plates Standard Deviation 1.30	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 36	0.8 Plates Standard Deviation 1.16	0.8 Plates Standard Deviation 1.05	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 40	0.5 Plates Standard Deviation 0.76	0.6 Plates Standard Deviation 0.81	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 44	1.0 Plates Standard Deviation 1.07	0.9 Plates Standard Deviation 1.31	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 48	1.3 Plates Standard Deviation 1.39	1.1 Plates Standard Deviation 1.34	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 52	1.6 Plates Standard Deviation 1.60	1.1 Plates Standard Deviation 1.09	—	—	—	—
Double Masked Period: Color Discrimination - Number of Plates Week 56 (Follow up)	1.7 Plates Standard Deviation 2.89	1.0 Plates Standard Deviation 1.00	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom Color Discrimination - Number of Plates by Visit was measured.

Open Label Extension Period: Change from Baseline in Color Discrimination - Number of Plates from Baseline by Visit by Ishihara Test. Score range: 0-38. Higher number equals better color discrimination equals better outcome. Lower number equals worse color discrimination equals worse outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 84	1.9 plates Standard Deviation 1.96	1.6 plates Standard Deviation 1.75	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 132	2.0 plates Standard Deviation 1.83	1.6 plates Standard Deviation 1.33	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 68	1.3 plates Standard Deviation 1.28	1.4 plates Standard Deviation 1.36	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 100	2.8 plates Standard Deviation 3.65	2.0 plates Standard Deviation 2.54	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 104	0.0 plates Standard Deviation 0.00	0.5 plates Standard Deviation 0.71	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 116	2.4 plates Standard Deviation 2.70	1.2 plates Standard Deviation 1.92	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 148	1.0 plates Standard Deviation 0.82	0.9 plates Standard Deviation 0.35	—	—	—	—
Open Label Extension Period: Change From Baseline in Color Discrimination - Number of Plates by Visit Week 160	2.0 plates Standard Deviation 2.00	1.3 plates Standard Deviation 1.53	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline to Week 56 (follow-up visit)

Population: All participants for whom Contrast sensitivity was measured.

Letters are arranged on a 60 x 85 cm chart in sets of triplets which contain the same contrast, decreasing in log10 contrast from top to bottom and left to right as participant progresses from one triplet to the other. Each group of three letters is decreased in contrast by a factor 0.71 (1/√2) (log contrast 0.15) of the proceeding set. Participant reads letters, starting with highest contrast, until unable to read letters in a single group. Score is based on the contrast of the last group read correctly.The size of the letters on the chart subtend 0.5 degrees at 3m, The test is scored in LogCS units, where each set of triplets advances in steps of 0.15 log units ranging from LogCS of 0.00 (approx. 100% contrast) to LogCS 2.25 (approx. 0.56% contrast). Change from baseline: the more negative the number means poor outcome, the more positive the number means better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 24	0.075 score on a scale Standard Deviation 0.1134	0.028 score on a scale Standard Deviation 0.1663	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Day 5	0.075 score on a scale Standard Deviation 0.0802	-0.019 score on a scale Standard Deviation 0.1078	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 4	0.038 score on a scale Standard Deviation 0.0694	-0.028 score on a scale Standard Deviation 0.1366	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 8	0.075 score on a scale Standard Deviation 0.1134	0.047 score on a scale Standard Deviation 0.1420	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 12	0.056 score on a scale Standard Deviation 0.1116	0.000 score on a scale Standard Deviation 0.1342	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 16	0.075 score on a scale Standard Deviation 0.1134	-0.009 score on a scale Standard Deviation 0.1020	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 20	0.094 score on a scale Standard Deviation 0.1116	-0.009 score on a scale Standard Deviation 0.1020	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 28	0.113 score on a scale Standard Deviation 0.1747	-0.009 score on a scale Standard Deviation 0.1393	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 32	0.113 score on a scale Standard Deviation 0.1553	0.028 score on a scale Standard Deviation 0.1663	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 36	0.150 score on a scale Standard Deviation 0.1604	0.056 score on a scale Standard Deviation 0.1806	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 40	0.206 score on a scale Standard Deviation 0.1782	0.075 score on a scale Standard Deviation 0.1975	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 44	0.225 score on a scale Standard Deviation 0.2268	0.066 score on a scale Standard Deviation 0.2625	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 48	0.188 score on a scale Standard Deviation 0.2232	0.084 score on a scale Standard Deviation 0.1446	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 52	0.225 score on a scale Standard Deviation 0.2121	0.075 score on a scale Standard Deviation 0.2258	—	—	—	—
Double Masked Period: Change From Baseline in Contrast Sensitivity by Pelli-Robson Contrast Sensitivity Chart by Visit Week 56 (Follow up)	0.100 score on a scale Standard Deviation 0.0866	0.050 score on a scale Standard Deviation 0.0866	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from Baseline from Week 68 to Week 160

Population: All participants for whom Contrast Sensitivity was measured.

Letters are arranged on a 60 x 85 cm chart in sets of triplets which contain the same contrast, decreasing in log10 contrast from top to bottom and left to right as participant progresses from one triplet to the other. Each group of three letters is decreased in contrast by a factor 0.71 (1/√2) (log contrast 0.15) of the proceeding set. Participant reads letters, starting with highest contrast, until unable to read letters in a single group. Score is based on the contrast of the last group read correctly. The size of the letters on the chart subtend 0.5 degrees at 3m, The test is scored in LogCS units, where each set of triplets advances in steps of 0.15 log units ranging from LogCS of 0.00 (approx. 100% contrast) to LogCS 2.25 (approx. 0.56% contrast). Change from baseline: the more negative the number means poor outcome, the more positive the number means better outcome.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 68	0.225 score on a scale Standard Deviation 0.2121	0.084 score on a scale Standard Deviation 0.1972	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 84	0.300 score on a scale Standard Deviation 0.1964	0.122 score on a scale Standard Deviation 0.1991	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 100	0.281 score on a scale Standard Deviation 0.2034	0.118 score on a scale Standard Deviation 0.2893	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 104	0.075 score on a scale Standard Deviation 0.1061	0.075 score on a scale Standard Deviation 0.1061	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 116	0.300 score on a scale Standard Deviation 0.3000	0.196 score on a scale Standard Deviation 0.2626	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 132	0.214 score on a scale Standard Deviation 0.1909	0.127 score on a scale Standard Deviation 0.2796	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 148	0.225 score on a scale Standard Deviation 0.2598	0.113 score on a scale Standard Deviation 0.1553	—	—	—	—
Open Label Extension Period: Change From Baseline in Contrast Sensitivity by Visit Week 160	0.150 score on a scale Standard Deviation 0.2598	0.100 score on a scale Standard Deviation 0.0866	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline and Week 52 (end-of-treatment visit)

Population: All participants for whom Retinal Ganglion Cell Layer Thickness was measured.

Change from baseline in Retinal Ganglion Cell Layer Thickness by SD-OCT From Baseline by Visit

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Change From Baseline in Retinal Ganglion Cell Layer Thickness	-1.5 µm Standard Deviation 4.00	-3.6 µm Standard Deviation 13.49	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 148,

Population: All participants for whom Change from baseline in Retinal Ganglion Cell Layer Thickness by SD-OCT was measured.

Open Label Extension Period: Change from baseline in Retinal Ganglion Cell Layer Thickness by SD-OCT by SD-OCT by visit

Outcome measures

Measure	Single Eye in DM Period n=1 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=5 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Change From Baseline in Retinal Ganglion Cell Layer Thickness	-1.0 µm	3.4 µm Standard Deviation 6.07	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Distance Activities was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Distance Activities score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Distance Activities Score Week 52	9.4 score on a scale Standard Deviation 12.94	0.0 score on a scale Standard Deviation 14.03	—	—	—	—
Double Masked: VFQ-39 Distance Activities Score Week 56 (Follow-up Visit)	54.2 score on a scale Standard Deviation 14.43	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Distance Activities score was measured.

Change in Visual Function Questionnaire (VFQ-39) Distance Activities Score.National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=3 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Distance Activities Score	12.5 score on a scale Standard Deviation 20.56	13.9 score on a scale Standard Deviation 6.36	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Social Functioning score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Social Functioning Score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Social Functioning Score	8.3 score on a scale Standard Deviation 11.78	5.6 score on a scale Standard Deviation 17.35	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Social Functioning was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Social Functioning score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Social Functioning Score. Week 52	6.3 score on a scale Standard Deviation 10.68	0.0 score on a scale Standard Deviation 19.25	—	—	—	—
Double Masked: VFQ-39 Social Functioning Score. Week 56 (Follow-up Visit)	16.7 score on a scale Standard Deviation 8.34	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Mental Health was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Mental Health score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Mental Health Score Week 52	12.0 score on a scale Standard Deviation 9.16	19.7 score on a scale Standard Deviation 32.47	—	—	—	—
Double Masked: VFQ-39 Mental Health Score Week 56 (Follow-up Visit)	13.3 score on a scale Standard Deviation 25.17	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Mental Health score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Mental Health Score . National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=3 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Mental Health Score	16.4 score on a scale Standard Deviation 22.31	29.2 score on a scale Standard Deviation 29.83	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Role Difficulties was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Role Difficulties score National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Role Difficulties Score Week 52	4.7 score on a scale Standard Deviation 10.43	14.1 score on a scale Standard Deviation 9.38	—	—	—	—
Double Masked: VFQ-39 Role Difficulties Score Week 56 (Follow-up Visit)	10.4 score on a scale Standard Deviation 13.01	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Role Difficulties score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Role Difficulties Score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Role Difficulties Score	8.0 score on a scale Standard Deviation 12.87	37.5 score on a scale Standard Deviation 16.54	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Dependency Score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39 ) Dependency Score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period:VFQ-39 Dependency Score	16.1 score on a scale Standard Deviation 13.91	27.1 score on a scale Standard Deviation 3.61	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Dependency score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Dependency score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Dependency Score Week 52	9.4 score on a scale Standard Deviation 22.10	-2.6 score on a scale Standard Deviation 24.85	—	—	—	—
Double Masked: VFQ-39 Dependency Score Week 56 (Follow-up Visit)	-8.3 score on a scale Standard Deviation 23.66	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Color Vision score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Color Vision score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Color Vision Score Week 52	6.3 score on a scale Standard Deviation 17.68	6.3 score on a scale Standard Deviation 12.50	—	—	—	—
Double Masked: VFQ-39 Color Vision Score Week 56 (Follow-up Visit)	0.0 score on a scale Standard Deviation 25.00	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Color Vision Score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Color Vision score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=6 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: VFQ-39 Color Vision Score	-7.1 score on a scale Standard Deviation 18.90	8.3 score on a scale Standard Deviation 14.43	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 Peripheral score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Peripheral Score . National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 Peripheral Score Week 52	0.0 score on a scale Standard Deviation 13.36	6.3 score on a scale Standard Deviation 12.50	—	—	—	—
Double Masked: VFQ-39 Peripheral Score Week 56 (Follow-up Visit)	66.7 score on a scale Standard Deviation 14.43	—	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 160 (End of OLE Period)

Population: All participants for whom Change in Visual Function Questionnaire (VFQ-39) Peripheral Score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) Peripheral Score . National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=7 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=3 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Visual Function Questionnaire (VFQ-39) Peripheral Score	0.0 score on a scale Standard Deviation 32.27	0.0 score on a scale Standard Deviation 25.00	—	—	—	—

SECONDARY outcome

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)

Population: All participants for whom intraocular Pressure (IOP) was measured

Double Masked Period: Change in intraocular Pressure (IOP) in mmHg from Baseline by Visit

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked Period: Change in Intraocular Pressure (IOP) Day 5	-0.3 mmHg Standard Deviation 1.67	-0.2 mmHg Standard Deviation 1.87	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 4	0.0 mmHg Standard Deviation 3.16	-0.4 mmHg Standard Deviation 2.16	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 8	-0.4 mmHg Standard Deviation 1.77	-0.5 mmHg Standard Deviation 1.83	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 12	0.5 mmHg Standard Deviation 2.39	-0.5 mmHg Standard Deviation 2.53	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 16	0.4 mmHg Standard Deviation 1.51	0.6 mmHg Standard Deviation 3.14	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 20	0.4 mmHg Standard Deviation 1.85	-0.3 mmHg Standard Deviation 1.66	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 24	-0.1 mmHg Standard Deviation 3.31	-0.4 mmHg Standard Deviation 2.99	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 28	0.3 mmHg Standard Deviation 1.83	0.3 mmHg Standard Deviation 1.88	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 32	0.0 mmHg Standard Deviation 2.62	-0.3 mmHg Standard Deviation 1.92	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 36	-1.1 mmHg Standard Deviation 1.55	-1.3 mmHg Standard Deviation 1.96	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 40	0.3 mmHg Standard Deviation 2.25	-0.6 mmHg Standard Deviation 1.75	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 44	-0.4 mmHg Standard Deviation 2.00	-0.3 mmHg Standard Deviation 1.85	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 48	0.5 mmHg Standard Deviation 3.66	0.8 mmHg Standard Deviation 2.79	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 52	-1.0 mmHg Standard Deviation 1.20	-0.5 mmHg Standard Deviation 2.66	—	—	—	—
Double Masked Period: Change in Intraocular Pressure (IOP) Week 56 (follow up Visit)	-1.0 mmHg Standard Deviation 1.20	-0.5 mmHg Standard Deviation 2.66	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom intraocular pressure was measured.

Change from baseline in Intraocular Pressure (IOP) in mmHg by Visit.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Intraocular Pressure (IOP) Week 68	-0.4 mmHg Standard Deviation 1.60	0.8 mmHg Standard Deviation 2.49	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 84	1.4 mmHg Standard Deviation 3.29	0.4 mmHg Standard Deviation 2.37	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 100	-0.9 mmHg Standard Deviation 2.03	-0.2 mmHg Standard Deviation 2.22	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 104	1.5 mmHg Standard Deviation 2.12	-1.0 mmHg Standard Deviation 1.41	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 116	0.1 mmHg Standard Deviation 3.18	-0.5 mmHg Standard Deviation 2.63	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 132	0.1 mmHg Standard Deviation 1.35	0.1 mmHg Standard Deviation 1.80	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 148	1.3 mmHg Standard Deviation 2.06	-0.1 mmHg Standard Deviation 2.36	—	—	—	—
Open Label Extension Period: Intraocular Pressure (IOP) Week 160	0.7 mmHg Standard Deviation 0.58	-1.7 mmHg Standard Deviation 1.53	—	—	—	—

SECONDARY outcome

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

Population: All participants for who SLE was measured.

Open Label Extension: Shift in Slit Lamp Examination from Baseline by Visit: number of eyes that changed from normal or abnormal not clinically significant, to abnormal clinically significant for Vehicle Eyes

Outcome measures

Measure	Single Eye in DM Period n=8 Eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 Eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Eye Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lids Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Conjunctiva 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 84	1 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 100	1 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Cornea Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Anterior Chamber 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Iris Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 116	1 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Lens Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Vitreous Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Retina Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Optic nerve Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Macula Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Choroid Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Vehicle Eye Periphery 160	0 eyes	0 eyes	—	—	—	—

SECONDARY outcome

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

Population: All participants for who SLE was measured.

Open Label Extension: Shift in Slit Lamp Examination from Baseline by Visit: number of eyes that changed from normal or abnormal not clinically significant, to abnormal clinically significant for Elamipretide Eyes

Outcome measures

Measure	Single Eye in DM Period n=16 Eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 Eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Eye Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lids Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Conjunctiva 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Cornea Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Anterior Chamber 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Iris Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 116	1 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Lens Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Vitreous Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Retina Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Optic nerve Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Macula Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Choroid Week 160	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 68	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 84	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 100	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 104	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 116	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 132	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery Week 148	0 eyes	0 eyes	—	—	—	—
OLE: Slit Lamp Examination (SLE)-Elamipretide Eye Periphery 160	0 eyes	0 eyes	—	—	—	—

SECONDARY outcome

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)

Incidence of Change from normal or Abnormal, clinically insignificant to normal clinically significant

Outcome measures

Measure	Single Eye in DM Period n=8 Participants Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=12 Participants Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Conjunctiva: Week 28 Normal to Abnormal Clinically significant	1 eyes	1 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Conjunctiva: Week 44 Normal to Abnormal Clinically significant	1 eyes	1 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Conjunctiva Week 4 Normal to Abnormal Clinically significant	1 eyes	0 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Conjunctiva: Week 8 Normal to Abnormal Clinically significant	1 eyes	0 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Conjunctiva: Week 16 Normal to Abnormal Clinically significant	1 eyes	1 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Lids: Week 28 Normal to Abnormal Clinically significant	0 eyes	1 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Cornea: Week 32 Normal to Abnormal Clinically significant	0 eyes	2 eyes	—	—	—	—
Double Masked: Slit Lamp Changes From Baseline: Vehicle Eye and Elamipretide Eye Cornea: Week 44 Normal to Abnormal Clinically significant	1 eyes	1 eyes	—	—	—	—

SECONDARY outcome

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)

Population: All participants for whom dilated fundus was measured.

Double Masked: Dilated Fundus Changes from Baseline: Vehicle Eye and Elamipretide Eyes Incidence of Change from normal or Abnormal-clinically insignificant, to normal clinically significant

Outcome measures

Measure	Single Eye in DM Period n=8 Participants Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=12 Participants Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes	0 eyes	0 eyes	—	—	—	—

SECONDARY outcome

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

Population: All participants for whom dilated fundus was measured.

Incidence of Change from normal or Abnormal-clinically insignificant, to normal clinically significant

Outcome measures

Measure	Single Eye in DM Period n=8 Participants Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=16 Participants Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Open Label Extension Period: Dilated Fundus Changes From Baseline: Vehicle Eye and Elamipretide Eyes	0 eyes	0 eyes	—	—	—	—

SECONDARY outcome

Timeframe: Assessed at Baseline, Week 52 (end-of-treatment visit) and Week 56 (follow-up visit)

Population: All participants for whom VFQ-39 General Health score was measured.

Change from baseline in Visual Function Questionnaire (VFQ-39) General Health score. National Eye Institute VFQ-39 score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.

Outcome measures

Measure	Single Eye in DM Period n=8 eyes Participants who received 1% elamipretide BID in one eye and control (placebo) BID in paired eye in the DM Period, and then received 1% elamipretide BID in both eyes in the OLE Period.	Bilateral Eye in DM Period n=8 eyes Elamipretide to Elamipretide Eyes DM Period: 4 participants received 1% elamipretide in both eyes in DM Period and continued receiving 1% elamipretide in both eyes in the OLE Period	Vehicle Eyes: Severe 4 participants received vehicle in the left eye only, 4 participants received 1% elamipretide in the right eye only	Elamipretide Eyes: Mild 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Moderate 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes	Elamipretide Eyes: Severe 4 participants received 1% elamipretide in the left eye only, 4 participants received 1% elamipretide in the right eye only, 4 participants received 1% elamipretide in both eyes
Double Masked: VFQ-39 General Health Score Week 52	-3.8 score on a scale Standard Deviation 10.09	-0.6 score on a scale Standard Deviation 19.72	—	—	—	—
Double Masked: VFQ-39 General Health Score Week 56 (Follow-up Visit)	-5.8 score on a scale Standard Deviation 6.29	—	—	—	—	—

Adverse Events

One Eye DM Period

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Both Eyes DM Period

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

(One Eye DM Period) OLE

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

(Both Eyes DM) OLE Period

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	One Eye DM Period n=8 participants at risk One eye Double Masked (DM) Period One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to a single eye and one drop of vehicle topical ophthalmic solution BID in the fellow eye	Both Eyes DM Period n=4 participants at risk Both eyes Double Masked (DM) One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU).	(One Eye DM Period) OLE n=8 participants at risk Both eyes Open label Extension period One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU) (and one eye in DM period)	(Both Eyes DM) OLE Period n=4 participants at risk Both eyes Open label Extension period One drop elamipretide (MTP-131) 1% topical ophthalmic solution BID applied to both eyes (OU) (and both eyes in DM period)
Gastrointestinal disorders Abdominal pain upper	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Hepatobiliary disorders Drug-induced liver injury	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Immune system disorders Hypersensitivity	12.5% 1/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Infections and infestations Nasopharyngitis	25.0% 2/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	25.0% 2/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Infections and infestations Sinusitis	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Infections and infestations Bronchitis	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Infections and infestations Ear infection	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Infections and infestations Gastroenteritis viral	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Infections and infestations Influenza	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	25.0% 2/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Injury, poisoning and procedural complications Muscle strain	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Injury, poisoning and procedural complications Wrist fracture	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Investigations Blood cholesterol increased	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Investigations Blood glucose decreased	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	37.5% 3/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Metabolism and nutrition disorders Gout	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Nervous system disorders Dysgeusia	25.0% 2/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Nervous system disorders Migraine	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Renal and urinary disorders Nephrolithiasis	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Respiratory, thoracic and mediastinal disorders Cough	25.0% 2/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Gastrointestinal disorders Nausea	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
General disorders Pyrexia	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Immune system disorders Seasonal allergy	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Infections and infestations Pharyngitis streptococcal	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks
Nervous system disorders Headache	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Psychiatric disorders Alcoholism	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	0.00% 0/8 • Up to 112 weeks	25.0% 1/4 • Up to 112 weeks
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	0.00% 0/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks	12.5% 1/8 • Up to 112 weeks	0.00% 0/4 • Up to 112 weeks

Additional Information

Jim Carr, Pharm.D. Chief Clinical Development Officer

Stealth BioTherapeutics, Inc

Phone: 1-(617) 600-6888

Email: jim.carr@stealthbt.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60