Von Hippel-Lindau SyndromePhase 1/2NCT02859441
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
A Phase 1/2 study testing Ranibizumab and E10030 in people with Von Hippel-Lindau Syndrome, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
Background: People with Von-Hippel-Lindau (VHL) disease may experience significant vision loss as a result of retinal capillary hemangiomas (RCH), the most common and often earliest manifestation of VHL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Von Hippel-Lindau Syndrome
- What is being tested?
- Ranibizumab and E10030
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2017to 9 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must understand and sign the informed consent.
- Participant must be 18 years of age or older.
- Participant must have a diagnosis of VHL disease. In accordance with established criteria for diagnosis, any one of the following will be considered sufficient evidence that VHL disease is present:
- A family history of VHL disease plus one or more of the following lesions: RCH, spinal or cerebellar hemangioblastoma, pheochromocytoma, multiple pancreatic cysts, epididymal or broad ligament cystadenomas, multiple renal cysts or renal cell carcinoma before age 60 years.
- Presence of two or more hemangioblastomas of the retina or brain or a single hemangioblastoma in association with a visceral manifestation such as kidney or pancreatic cysts; renal cell carcinoma; adrenal or extra-adrenal pheochromocytomas; endolymphatic sac tumors; papillary cystadenomas of the epididymis or broad ligament; or neuroendocrine tumors of the pancreas.
- Presence of a known disease-causing germline mutation in the VHL gene.
Show all 21Show fewer
- Any female participant of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing immediately prior to each treatment.
- Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for at least two months following the last administration of combination investigational treatment. Acceptable methods of contraception include:
- hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
- intrauterine device,
- barrier methods (diaphragm or condom) with spermicide, or
- surgical sterilization (hysterectomy, tubal ligation or vasectomy).
- Participant has at least one RCH secondary to VHL disease in the study eye that fulfills the following criteria:
- The RCH must exhibit growth potential with consequent threat to vision. Growth potential with consequent threat to vision is defined by AT LEAST ONE of the following:
- Associated intra- or sub-retinal exudation or lipid deposition that, in the judgment of the investigator, reflects ongoing vascular incompetence and is not solely reflective of residual changes following previous treatment or solely secondary to coexistent retinal traction.
- Increased size of the tumor compared to a previous time point as assessed by fundus photography or FA.
- Associated intra-, sub- or pre-retinal hemorrhage not secondary to previous treatment, as assessed by fundus photography or FA.
- The presence of dilated and/or tortuous feeder vessels.
- Vitreous cell or haze indicative of vitreous exudation, in the absence of other ocular features potentially responsible for such findings.
- The RCH, in the judgment of the investigator, is NOT readily treatable using thermal laser because of its size, posterior location, poor previous response to conventional therapy, association with significant exudation, epiretinal proliferation, associated vascular abnormalities such as vascular proliferation or diffusely incompetent retinal vessels, or other factors predictive of a poor response to standard of care approaches.
- The study eye must have clarity of ocular media and degree of pupil dilation sufficient to permit adequate fundus photography.
Who cannot join
- Participant has a history or evidence of significant cardiac disease (for example, use of cardiac medications aside from agents to control blood pressure, past acute coronary syndrome, past myocardial infarction, past revascularization procedure or arrhythmias requiring past or present treatment).
- Participant has a history of stroke or transient ischemic attack.
- Note: cerebrovascular manifestations and/or complications of central nervous system hemangioblastomas are not exclusionary, in the absence of past stroke or transient ischemic attack.
- Participant has used systemic medication with significant anti-VEGF or anti-PDGF activity within 30 days of study entry or expects use of such a medication within 12 months of study entry.
- Participant is medically unable to comply with study procedures or follow-up in the judgment of the investigator.
- Participant has a diagnosis of diabetic mellitus (type 1 or type 2). Any one of the following will be considered sufficient evidence that diabetes is present:
Show all 20Show fewer
- Current regular use of insulin for the treatment of diabetes,
- Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes,
- Hemoglobin A1C of greater than or equal to 6.5%, or
- Documented diabetes by the American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.
- Study Eye Eligibility Criteria
- The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below.
- The study eye has present or chronic ocular or periocular infection (including any history of ocular herpes zoster).
- The study eye has chronic glaucoma; OR has received anti-glaucoma medication at any time within 90 days of study entry; OR has significant ocular hypertension, defined as documented intraocular pressure of greater than or equal to 28 mmHg on any occasion in the absence of self-limited acute glaucoma, OR greater than or equal to 24 mmHg on at least two occasions in the absence of self-limited acute glaucoma.
- Note: History of self-limited acute glaucoma in a study eye, if now resolved and not expected to recur, is not exclusionary. History of glaucoma or ocular hypertension in the fellow eye, if not felt to significantly impact risk of glaucoma in the study eye, is not exclusionary.
- The study eye has undergone any surgical procedure within 60 days prior to study entry (inclusive of cryotherapy or thermal laser).
- The study eye has a history of intravitreal injection of an anti-VEGF agent (such as bevacizumab, ranibizumab or aflibercept) within 42 days prior to study entry.
- The study eye has a history of intravitreal or periocular injection of long-acting corticosteroids (such as triamcinolone acetonide) within 90 days of study entry or history of any sustained-release ocular drug delivery device with reasonable expectation of residual activity in the study eye.
- Choice of Study Eye in Cases of Bilateral Eligibility
- If both eyes of a participant meet the criteria described above, the investigator will choose to enroll one eye in consultation with the participant.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background: People with Von-Hippel-Lindau (VHL) disease may experience significant vision loss as a result of retinal capillary hemangiomas (RCH), the most common and often earliest manifestation of VHL.
Objective: To investigate the safety and possible efficacy of combination investigational treatment with serial intravitreal injections of E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist, in participants with severe ocular VHL disease.
Read more
Design: Three participants with severe ocular VHL disease will receive the combination investigational treatment in one eye and will be followed for 104 weeks.
Primary Outcome: The safety of the combination investigational treatment, assessed by tabulation of adverse events reported through Week 52.
Read the detailed description
Objective: Von Hippel-Lindau (VHL) disease is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis and broad ligament. The disease affects about 7,000 individuals in the United States. Retinal capillary hemangiomas (RCH) are the most common and often the earliest manifestation of VHL disease and may lead to significant vision loss. In some such eyes, inexorable progression of RCH leads to blindness and phthisis bulbi despite aggressive treatment. Levels of vascular endothelial growth factor (VEGF), a potent mediator of angiogenesis and vascular permeability, have been shown to be elevated in multiple cell types deficient in the VHL protein (pVHL). Platelet-derived growth factor (PDGF), which has an important role in stabilization of immature new vessels during angiogenesis, is upregulated in pVHL-defective cell lines and expressed in other pVHL-defective tumors. Anti-VEGF therapy alone had no beneficial effect on ocular VHL disease in two previous phase 1 studies. The objective of this study is to investigate the safety and possible efficacy of combination investigational treatment with serial intravitreal injections of E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist, in participants with severe ocular VHL disease.
Study Population: Three participants with severe ocular VHL disease will receive the combination investigational treatment in one eye and will be followed for 104 weeks.
Design: In this phase I/II, single-center, prospective, open label, non-randomized, uncontrolled, single group trial, one eye of eligible participants will be treated with investigational products, E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist. Participants will receive combination investigational treatment consisting of intravitreal injections of E10030 (1.5 mg in 0.05 mL) and ranibizumab (0.5 mg in 0.05 mL) every four weeks from baseline through Week 16 (totaling five treatments) and then every eight weeks through Week 48 (totaling nine treatments from baseline). All participants will be followed for 104 weeks.
Outcome Measures: The primary outcome for the study will be safety of the combination investigational treatment, assessed by tabulation of adverse events reported through Week 52. Secondary outcomes will include tabulation of adverse events at Week 104, and the following measures in the study eye at Week 52 and 104: 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)); 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); mean change in visual acuity; change in size of RCH (measured by fundus photography and FA); change in exudation (measured by fundus photography, optical coherence tomography (OCT) and FA); change in epiretinal proliferation, fibrosis or retinal traction (assessed by OCT and fundus photography); proportion of participants undergoing ablative treatment of RCH or ocular surgery; proportion of participants with successful ablative treatment of RCH; and the proportion of participants with appearance of one or more new RCH.
- Conditions
- Von Hippel-Lindau Syndrome
- Being tested
- Ranibizumab, E10030
- Keywords
- Intravitreal Injection, Retinal Capillary Hemangioma
- Medical subject headings
- von Hippel-Lindau Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
Intravitreal injections of the commercially-available 10 mg/mL formulation of ranibizumab. Ranibizumab is formulated as a sterile solution (pH 5.5) with histidine, trehalose and polysorbate 20. The vial contains no preservative. Each vial contains 0.5 mL of 10 mg/mL ranibizumab aqueous solution. The intravitreal injection volume of ranibizumab is 50 microliter, which correlates to 0.5 mg of dry ranibizumab.
E10030Drug
E10030 is not a commercially available drug product, and will be provided by Ophthotech Corp. The drug product is provided as a sterile aqueous solution of E10030 at a concentration of 30 mg (oligo weight)/mL. The solution contains monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate as buffering agents as well as sodium chloride as a tonicity adjuster. The intravitreal injection volume of E10030 is 50 microliter, which correlates to 1.5 mg of dry E10030.
| Study group | Role | What they receive |
|---|---|---|
| E10030 and Ranibizumab | Experimental | Intravitreal injections of E10030 and Ranibizumab Receives: Drug: Ranibizumab; Drug: E10030 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tabulation of Adverse Events
The total number of adverse events through Week 52.
Measured: From Baseline to Week 52
Secondary outcomes (19)
Tabulation of Adverse Events
The total number of adverse events, excluding natural progression of disease events, through Week 104.
Measured: From Baseline to Week 104
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))
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.
Measured: From Baseline to Week 52
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])
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.
Measured: From Baseline to Week 104
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery
The proportion of participants undergoing ablative treatment of RCH or ocular surgery in the study eye between Baseline and Week 52.
Measured: From Baseline to Week 52
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery
The proportion of participants undergoing ablative treatment of RCH or ocular surgery in the study eye between Baseline and Week 104.
Measured: From Baseline to Week 104
Proportion of Participants With Successful Ablative Treatment of RCH
The proportion of participants with successful ablative treatment of RCH in the study eye between Baseline and Week 52.
Measured: From Baseline to Week 52
Proportion of Participants With Successful Ablative Treatment of RCH
The proportion of participants with successful ablative treatment of RCH in the study eye between Baseline and Week 104.
Measured: From Baseline to Week 104
Mean Change in Visual Acuity
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.
Measured: Baseline and Week 52
Mean Change in Visual Acuity
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.
Measured: Baseline and Week 104
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)
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.
Measured: From Baseline to Week 52
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)
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.
Measured: From Baseline to Week 104
Change in Size of RCH (Measured by Fundus Photography and FA)
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).
Measured: From Baseline to Week 52
Change in Size of RCH (Measured by Fundus Photography and FA)
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).
Measured: From Baseline to Week 104
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography (OCT) and FA)
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).
Measured: From Baseline to Week 52
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography [OCT] and FA)
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).
Measured: From Baseline to Week 104
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)
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).
Measured: From Baseline to Week 52
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)
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).
Measured: From Baseline to Week 104
Proportion of Participants With Appearance of One or More New RCH
The proportion of participants with appearance of one or more new RCH in the study eye between Baseline and Week 52.
Measured: From Baseline to Week 52
Proportion of Participants With Appearance of One or More New RCH
The proportion of participants with appearance of one or more new RCH in the study eye between Baseline and Week 104.
Measured: From Baseline to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study start23 Jan 2017
- Primary completion9 Jul 2019
- Study completion9 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Von Hippel-Lindau SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Henry E Wiley, M.D., Principal investigator, National Eye Institute (NEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02859441
- Sponsor's protocol ID
- 160159
- Other IDs
- 16-EI-0159
- Status last verified
- Jul 2019
- First submitted
- 6 Aug 2016
- Last updated
- 1 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hwang CK, Chew EY, Cukras CA, Keenan TDL, Wong WT, Linehan WM, Chittiboina P, Pacak K, Wiley HE. Intravitreous treatment of severe ocular von Hippel-Lindau disease using a combination of the VEGF inhibitor, ranibizumab and PDGF inhibitor, E10030: Results from a phase 1/2 clinical trial. Clin Exp Ophthalmol. 2021 Dec;49(9):1048-1059. doi: 10.1111/ceo.14001. Epub 2021 Oct 26.
PubMed 34549489
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02859441
- Acronym / sponsor ID
- 160159
- Conditions
- Von Hippel-Lindau Syndrome
- Keywords
- Intravitreal Injection, Retinal Capillary Hemangioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 23 Jan 2017 (actual)
- Primary completion
- 9 Jul 2019 (actual)
- Study completion
- 9 Jul 2019 (actual)
- First posted
- 9 Aug 2016 (estimated)
- Results
- Posted 14 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: People with Von-Hippel-Lindau (VHL) disease may experience significant vision loss as a result of retinal capillary hemangiomas (RCH), the most common and often earliest manifestation of VHL.
Objective: To investigate the safety and possible efficacy of combination investigational treatment with serial intravitreal injections of E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist, in participants with severe ocular VHL disease.
Design: Three participants with severe ocular VHL disease will receive the combination investigational treatment in one eye and will be followed for 104 weeks.
Primary Outcome: The safety of the combination investigational treatment, assessed by tabulation of adverse events reported through Week 52.
Detailed description
Objective: Von Hippel-Lindau (VHL) disease is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis and broad ligament. The disease affects about 7,000 individuals in the United States. Retinal capillary hemangiomas (RCH) are the most common and often the earliest manifestation of VHL disease and may lead to significant vision loss. In some such eyes, inexorable progression of RCH leads to blindness and phthisis bulbi despite aggressive treatment. Levels of vascular endothelial growth factor (VEGF), a potent mediator of angiogenesis and vascular permeability, have been shown to be elevated in multiple cell types deficient in the VHL protein (pVHL). Platelet-derived growth factor (PDGF), which has an important role in stabilization of immature new vessels during angiogenesis, is upregulated in pVHL-defective cell lines and expressed in other pVHL-defective tumors. Anti-VEGF therapy alone had no beneficial effect on ocular VHL disease in two previous phase 1 studies. The objective of this study is to investigate the safety and possible efficacy of combination investigational treatment with serial intravitreal injections of E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist, in participants with severe ocular VHL disease.
Study Population: Three participants with severe ocular VHL disease will receive the combination investigational treatment in one eye and will be followed for 104 weeks.
Design: In this phase I/II, single-center, prospective, open label, non-randomized, uncontrolled, single group trial, one eye of eligible participants will be treated with investigational products, E10030, a PDGF-B antagonist, and ranibizumab, a VEGF-A antagonist. Participants will receive combination investigational treatment consisting of intravitreal injections of E10030 (1.5 mg in 0.05 mL) and ranibizumab (0.5 mg in 0.05 mL) every four weeks from baseline through Week 16 (totaling five treatments) and then every eight weeks through Week 48 (totaling nine treatments from baseline). All participants will be followed for 104 weeks.
Outcome Measures: The primary outcome for the study will be safety of the combination investigational treatment, assessed by tabulation of adverse events reported through Week 52. Secondary outcomes will include tabulation of adverse events at Week 104, and the following measures in the study eye at Week 52 and 104: 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)); 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); mean change in visual acuity; change in size of RCH (measured by fundus photography and FA); change in exudation (measured by fundus photography, optical coherence tomography (OCT) and FA); change in epiretinal proliferation, fibrosis or retinal traction (assessed by OCT and fundus photography); proportion of participants undergoing ablative treatment of RCH or ocular surgery; proportion of participants with successful ablative treatment of RCH; and the proportion of participants with appearance of one or more new RCH.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| E10030 and Ranibizumab | Experimental | Drug: Ranibizumab, Drug: E10030Intravitreal injections of E10030 and Ranibizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Participant must understand and sign the informed consent.
- Participant must be 18 years of age or older.
- Participant must have a diagnosis of VHL disease. In accordance with established criteria for diagnosis, any one of the following will be considered sufficient evidence that VHL disease is present:
- Any female participant of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing immediately prior to each treatment.
- Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for at least two months following the last administration of combination investigational treatment. Acceptable methods of contraception include:
Key exclusion criteria (20 listed)
- Participant has a history or evidence of significant cardiac disease (for example, use of cardiac medications aside from agents to control blood pressure, past acute coronary syndrome, past myocardial infarction, past revascularization procedure or arrhythmias requiring past or present treatment).
- Participant has a history of stroke or transient ischemic attack.
- Note: cerebrovascular manifestations and/or complications of central nervous system hemangioblastomas are not exclusionary, in the absence of past stroke or transient ischemic attack.
- Participant has used systemic medication with significant anti-VEGF or anti-PDGF activity within 30 days of study entry or expects use of such a medication within 12 months of study entry.
- Participant is medically unable to comply with study procedures or follow-up in the judgment of the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanibizumabIntravitreal injections of the commercially-available 10 mg/mL formulation of ranibizumab. Ranibizumab is formulated as a sterile solution (pH 5.5) with histidine, trehalose and polysorbate 20. The vial contains no preservative. Each vial contains 0.5 mL of 10 mg/mL ranibizumab aqueous solution. The intravitreal injection volume of ranibizumab is 50 microliter, which correlates to 0.5 mg of dry ranibizumab. | Drug | E10030 and Ranibizumab |
| E10030E10030 is not a commercially available drug product, and will be provided by Ophthotech Corp. The drug product is provided as a sterile aqueous solution of E10030 at a concentration of 30 mg (oligo weight)/mL. The solution contains monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate as buffering agents as well as sodium chloride as a tonicity adjuster. The intravitreal injection volume of E10030 is 50 microliter, which correlates to 1.5 mg of dry E10030. | Drug | E10030 and Ranibizumab |
Primary outcome
Tabulation of Adverse Events
Time frame: From Baseline to Week 52
The total number of adverse events through Week 52.
19 secondary outcomes
Tabulation of Adverse Events
Time frame: From Baseline to Week 104
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))
Time frame: From Baseline to Week 52
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])
Time frame: From Baseline to Week 104
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery
Time frame: From Baseline to Week 52
Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery
Time frame: From Baseline to Week 104
Proportion of Participants With Successful Ablative Treatment of RCH
Time frame: From Baseline to Week 52
Proportion of Participants With Successful Ablative Treatment of RCH
Time frame: From Baseline to Week 104
Mean Change in Visual Acuity
Time frame: Baseline and Week 52
Mean Change in Visual Acuity
Time frame: Baseline and Week 104
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)
Time frame: From Baseline to Week 52
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)
Time frame: From Baseline to Week 104
Change in Size of RCH (Measured by Fundus Photography and FA)
Time frame: From Baseline to Week 52
Change in Size of RCH (Measured by Fundus Photography and FA)
Time frame: From Baseline to Week 104
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography (OCT) and FA)
Time frame: From Baseline to Week 52
Change in Exudation (Measured by Fundus Photography, Optical Coherence Tomography [OCT] and FA)
Time frame: From Baseline to Week 104
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)
Time frame: From Baseline to Week 52
Change in Epiretinal Proliferation, Fibrosis or Retinal Traction (Assessed by OCT and Fundus Photography)
Time frame: From Baseline to Week 104
Proportion of Participants With Appearance of One or More New RCH
Time frame: From Baseline to Week 52
Proportion of Participants With Appearance of One or More New RCH
Time frame: From Baseline to Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34549489Hwang CK, Chew EY, Cukras CA, Keenan TDL, Wong WT, Linehan WM, Chittiboina P, Pacak K, Wiley HE. Intravitreous treatment of severe ocular von Hippel-Lindau disease using a combination of the VEGF inhibitor, ranibizumab and PDGF inhibitor, E10030: Results from a phase 1/2 clinical trial. Clin Exp Ophthalmol. 2021 Dec;49(9):1048-1059. doi: 10.1111/ceo.14001. Epub 2021 Oct 26.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Von Hippel-Lindau Syndrome
RecruitingObservational study
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders
Kidney Cancer, Urologic Malignant Disorders
RecruitingPhase 2
Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor
Enrolling by invitation
Use of Tracking Devices to Locate Abnormalities During Invasive Procedures
Adenocarcinoma, Prostate Neoplasms
RecruitingObservational study
National Eye Institute Biorepository for Retinal Diseases
Age-Related Macular Degeneration, Diabetic Retinopathy
RecruitingObservational study
Belzutifan VHL RCC HK Prospective Registry
VHL - Von Hippel-Lindau Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henry E Wiley, M.D. principal investigator
National Eye Institute (NEI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ranibizumab and E10030 in people with Von Hippel-Lindau Syndrome, run by National Eye Institute (NEI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tabulation of Adverse Events (time frame: From Baseline to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02859441, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.