Trial Outcomes & Findings for A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab (NCT NCT02859441)

NCT ID: NCT02859441

Last Updated: 2021-11-01

Results Overview

The total number of adverse events through Week 52.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 3 participants
• Primary outcome timeframe: From Baseline to Week 52
• Results posted on: 2021-11-01

Participant Flow

Participant milestones

Measure	E10030 and Ranibizumab Intravitreal injections of E10030 and Ranibizumab
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab

Baseline characteristics by cohort

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	44.7 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 52

The total number of adverse events through Week 52.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Tabulation of Adverse Events	13 adverse events	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 104

The total number of adverse events, excluding natural progression of disease events, through Week 104.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Tabulation of Adverse Events	27 adverse events	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

The proportion of participants experiencing a reduction in size of at least one RCH in the study eye, in the absence of other ablative treatment as assessed by fundus photography and fluorescein angiography (FA), between Baseline and Week 52.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
The Proportion of Participants Experiencing Reduction in Size of at Least One Retinal Capillary Hemangioma (RCH), in the Absence of Other Ablative Treatment (Assessed by Fundus Photography and Fluorescein Angiography (FA))	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 104

The proportion of participants experiencing a reduction in size of at least one RCH in the study eye, in the absence of other ablative treatment as assessed by fundus photography and fluorescein angiography (FA), between Baseline and Week 104.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
The Proportion of Participants Experiencing Reduction in Size of at Least One RCH, in the Absence of Other Ablative Treatment (Assessed by Fundus Photography and Fluorescein Angiography [FA])	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

The proportion of participants undergoing ablative treatment of RCH or ocular surgery in the study eye between Baseline and Week 52.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 104

The proportion of participants undergoing ablative treatment of RCH or ocular surgery in the study eye between Baseline and Week 104.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: No participants were analyzed for this outcome because none of the participants underwent ablative treatment of RCH. Therefore, no data was collected for this outcome.

The proportion of participants with successful ablative treatment of RCH in the study eye between Baseline and Week 52.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Baseline to Week 104

Population: No participants were analyzed for this outcome because none of the participants underwent ablative treatment of RCH. Therefore, no data was collected for this outcome.

The proportion of participants with successful ablative treatment of RCH in the study eye between Baseline and Week 104.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Mean visual acuity values are presented for Baseline and Week 52 and the mean change at Week 52 from Baseline for the study eye.

Mean change in visual acuity in the study eye from Baseline as compared to Week 52 as measured using the Electronic Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity (EVA) Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Mean Change in Visual Acuity	64.0 Letters Read Standard Deviation 26.3	59.0 Letters Read Standard Deviation 21.3	-5.0 Letters Read Standard Deviation 7.0	—

SECONDARY outcome

Timeframe: Baseline and Week 104

Population: Mean visual acuity values are presented for Baseline and Week 104 and the mean change at Week 104 from Baseline for the study eye.

Mean change in visual acuity in the study eye from Baseline as compared to Week 104 as measured using the Electronic Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity (EVA) Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Mean Change in Visual Acuity	64.0 Letters Read Standard Deviation 26.3	45.0 Letters Read Standard Deviation 40.1	-19.0 Letters Read Standard Deviation 14.1	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

The proportion of participants experiencing moderate vision loss in the study eye (defined as a loss of greater than or equal to 15 letters from baseline on Electronic Visual Acuity [EVA] testing) between Baseline and Week 52.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
The Proportion of Participants Experiencing Moderate Vision Loss (Defined as a Loss of Greater Than or Equal to 15 Letters From Baseline on Electronic Visual Acuity [EVA] Testing)	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 104

The proportion of participants experiencing moderate vision loss in the study eye (defined as a loss of greater than or equal to 15 letters from baseline on Electronic Visual Acuity [EVA] testing) between Baseline and Week 104.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
The Proportion of Participants Experiencing Moderate Vision Loss (Defined as a Loss of Greater Than or Equal to 15 Letters From Baseline on Electronic Visual Acuity [EVA] Testing)	2 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

Number of participants who experienced increased, decreased, or mixed change in the size of RCH in the study eye between Baseline and Week 52 (measured by fundus photography and FA).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Size of RCH (Measured by Fundus Photography and FA)	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 104

Number of participants who experienced increased, decreased, or mixed change in the size of RCH in the study eye between Baseline and Week 104 (measured by fundus photography and FA).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Size of RCH (Measured by Fundus Photography and FA)	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

Number of participants who experienced increased, decreased, or mixed change in exudation in the study eye between Baseline and Week 52 (measured by fundus photography, optical coherence tomography [OCT] and FA).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography (OCT) and FA)	1 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 104

Number of participants who experienced increased, decreased, or mixed change in exudation in the study eye between Baseline and Week 104 (measured by fundus photography, optical coherence tomography [OCT] and FA).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography [OCT] and FA)	1 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

Number of participants who experienced increased, decreased, or mixed change in epiretinal proliferation, fibrosis or retinal traction in the study eye between Baseline and Week 52 (assessed by OCT and fundus photography).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 104

Number of participants who experienced increased, decreased, or mixed change in epiretinal proliferation, fibrosis or retinal traction in the study eye between Baseline and Week 104 (assessed by OCT and fundus photography).

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline n=3 Participants Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH n=3 Participants Intravitreal injections of E10030 and Ranibizumab
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

The proportion of participants with appearance of one or more new RCH in the study eye between Baseline and Week 52.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Proportion of Participants With Appearance of One or More New RCH	0 Participants	—	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 104

The proportion of participants with appearance of one or more new RCH in the study eye between Baseline and Week 104.

Outcome measures

Measure	E10030 and Ranibizumab n=3 Participants Intravitreal injections of E10030 and Ranibizumab	Visual Acuity at Week 52 Intravitreal injections of E10030 and Ranibizumab	Mean Change in Visual Acuity at Week 52 From Baseline Intravitreal injections of E10030 and Ranibizumab	No Change in Size of RCH Intravitreal injections of E10030 and Ranibizumab
Proportion of Participants With Appearance of One or More New RCH	1 Participants	—	—	—

Adverse Events

E10030 and Ranibizumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	E10030 and Ranibizumab n=3 participants at risk Intravitreal injections of E10030 and Ranibizumab
Renal and urinary disorders Nephrolithiasis	33.3% 1/3 • Number of events 2 • 104 Weeks Adverse events were collected on and after the baseline visit.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.

Other adverse events

Measure	E10030 and Ranibizumab n=3 participants at risk Intravitreal injections of E10030 and Ranibizumab
Eye disorders Ocular Hypertension	33.3% 1/3 • Number of events 3 • 104 Weeks Adverse events were collected on and after the baseline visit.
Musculoskeletal and connective tissue disorders Back Pain	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Nervous system disorders Hypoaesthesia	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Infections and infestations Infection	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Posterior Capsule Opacification	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Visual Acuity Reduced	66.7% 2/3 • Number of events 3 • 104 Weeks Adverse events were collected on and after the baseline visit.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Investigations Weight Decreased	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Eye Pain	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Injury, poisoning and procedural complications Limb Injury	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Vitreous Haemorrhage	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Inflammation	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Corneal Abrasion	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Keratopathy	33.3% 1/3 • Number of events 2 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Corneal Erosion	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Corneal Neovascularization	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Investigations Blood Pressure Increased	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Retinal Haemorrhage	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Congenital, familial and genetic disorders Von Hippel-Lindau Disease	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Congenital, familial and genetic disorders Haemangioma of Retina	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Iris Adhesions	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Surgical and medical procedures Eye Laser Surgery	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Eye Haemorrhage	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.
Eye disorders Iris Neovascularisation	33.3% 1/3 • Number of events 1 • 104 Weeks Adverse events were collected on and after the baseline visit.

Additional Information

Henry E Wiley, M.D., Principal Investigator, NEI

National Institutes of Health

Phone: 301-496-6583

Email: wileyhe@nei.nih.gov

Results disclosure agreements

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