Hippel-Lindau DiseasePhase 1NCT00056199
EYE001 to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome
A Phase 1 study testing EYE001 in people with Hippel-Lindau Disease, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will test the ability of the experimental drug EYE001 to reduce retinal thickening and improve vision in patients with Von Hippel-Lindau syndrome (VHL). Angiomas (blood vessel tumors) commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hippel-Lindau Disease
- What is being tested?
- EYE001
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2003to Nov 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient must understand and sign the informed consent.
- Patient must be at least 18 years of age.
- Patient must have retinal angiomas secondary to VHL in one or both eyes.
- Patient must have either optic nerve tumors or peripheral tumors that have caused central vision loss of 20/40 or worse.
- Patient must have clear ocular media and adequate papillary dilation to permit good quality stereoscopic fundus photography.
- Patients must be post menopausal, surgically sterile for at least 12 months prior to study entry, or agree to use at least two effective forms of birth control.
Show all 10Show fewer
- All women of childbearing potential must have a negative serum pregnancy test at baseline and immediately prior to each injection and for at least 60 days following the last dose of EYE001.
- Patient must have lab values indicative of adequate hematological function (hemoglobin greater than or equal to 10 g/dl, platelet count less than or equal to 130 x 10(9)/I, WBC 3.8-10.8 x 10(9)/I) within one month of baseline.
- Patients must have lab values indicative of adequate liver function (serum bilirubin less than or equal to 1.5 mg/dl, SGOT/ALT, SGPT/AST, GGT and alkaline phosphotase within 2 x ULN) within one month of baseline.
- Patients must have lab values indicative of adequate renal function serum creatinine less than or equal to 2.0 mg/dl and BUN within 2.0 x ULN within one month of baseline.
Who cannot join
- Significant media opacities, including cataract that precludes quality fundus photographs of the posterior pole.
- History or evidence of severe cardiac disease (electrocardiogram abnormalities, clinical history of unstable angina, acute coronary syndrome, myocardial infarction, revascularization procedure within 6 months prior to baseline, atrial or ventricular tachyarrythmias requiring ongoing treatment).
- History of stroke within 12 months of study entry.
- History of or current acute ocular or periocular infection (including any history of ocular herpes zoster).
- Any major surgical procedure within one month of study entry.
- Known serious allergies to fluorescein dye.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Eye Institute (NEI)
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Intravitreal Injection of EYE001 (Anti-VEGF Pegylated Aptamer) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease
This study will test the ability of the experimental drug EYE001 to reduce retinal thickening and improve vision in patients with Von Hippel-Lindau syndrome (VHL). Angiomas (blood vessel tumors) commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Although the tumors are not cancerous, they may cause significant vision loss. Current treatments, including laser therapy, cryotherapy, and vitrectomy, may not be successful or possible for all patients. EYE001 decreases production of VEGF, a growth factor that is important for the formation of new blood vessels and that is elevated in VHL. Preliminary findings from studies of other retinal diseases suggest that EYE001 can reduce retinal thickening and improve vision.
Patients 18 years of age and older with retinal angiomas due to VHL in one or both eyes and central vision loss of 20/40 or worse may be eligible for this study. Participants will undergo the following tests and procedures:
Read more
- Medical history, physical examination, electrocardiogram (EKG) and blood tests.
- Eye examination, including eye pressure measurement and dilation of the pupils to examine the retina.
- Fluorescein angiography to evaluate the eye's blood vessels. For this test, a yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures will reveal if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
- Optical coherence tomography to measure retinal thickness. The eyes are examined through a machine that produces cross-sectional pictures of the retina. These measures are repeated during the study to determine changes, if any, in retinal thickening.
- Electroretinogram (ERG) to measure electrical responses generated from within the retina. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside an open white globe that emits a series of light flashes for about 20 minutes. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Stereoscopic color fundus photography to examine the back of the eye. The pupils are dilated with eye drops to examine and photograph the back of the eye.
- EYE001 injections to treat ocular angiomas. Patients receive EYE001 injections through a needle into the eye's vitreous (gel-like substance that fills the inside of the eye). Six injections are given over a 30-week period. Before each injection, the surface of the eye is numbed with anesthetic eye drops. This is followed by injection of another anesthetic into the lower portion of they eye in the clear tissue surrounding the white of the eye. After a few minutes, the EYE001 is injected into the vitreous. Patients receive EYE001 injections at the first visit (during enrollment) and again at 6, 12, 18, 24, and 30 weeks after the first injection.
At each injection visit, participants repeat most of the tests described above to evaluate the response to treatment and return a week later for another eye examination. After the last injection, patients whose vision has improved may receive three more treatments at visits 36, 42, and 48. All participants will return for examinations at week 54 and at 2 months after their final injection.
Read the detailed description
Von Hippel-Lindau (VHL) 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. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of anti-VEGF therapy (EYE001) in 5 patients to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Patients will receive 6 intravitreal injections of study drug over a 30-week period, then return for a follow-up visit 1 year after initiating injections. The primary outcomes will be improvement in best corrected visual acuity of 15 letters or more at 1 year, reduction in retinal thickening and leakage at one year, changes in ERG amplitude and implicit time, and adverse events including local and systemic toxicities.
- Conditions
- Hippel-Lindau Disease
- Being tested
- EYE001
- Keywords
- Vision Loss, Optic Nerve Tumors, Macular Edema, Von Hippel-Lindau Disease, VEGF, EYE001, VHL
- Medical subject headings
- von Hippel-Lindau Disease, Vision Disorders, Optic Nerve Neoplasms, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EYE001Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2003 (estimated)
- Study startMar 2003
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hippel-Lindau DiseaseStudies 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
- Primary purpose
- Treatment
- Enrolment
- 5 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00056199
- Sponsor's protocol ID
- 030101
- Other IDs
- 03-EI-0101
- Status last verified
- Nov 2005
- First submitted
- 7 Mar 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995 Mar;194(3):629-42. doi: 10.1148/radiology.194.3.7862955.
PubMed 7862955Libutti SK, Choyke PL, Alexander HR, Glenn G, Bartlett DL, Zbar B, Lubensky I, McKee SA, Maher ER, Linehan WM, Walther MM. Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease. Surgery. 2000 Dec;128(6):1022-7;discussion 1027-8. doi: 10.1067/msy.2000.110239.
PubMed 11114638Manski TJ, Heffner DK, Glenn GM, Patronas NJ, Pikus AT, Katz D, Lebovics R, Sledjeski K, Choyke PL, Zbar B, Linehan WM, Oldfield EH. Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. JAMA. 1997 May 14;277(18):1461-6. doi: 10.1001/jama.277.18.1461.
PubMed 9145719
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Intravitreal Injection of EYE001 (Anti-VEGF Pegylated Aptamer) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease
- ClinicalTrials.gov ID
- NCT00056199
- Acronym / sponsor ID
- 030101
- Conditions
- Hippel-Lindau Disease
- Keywords
- Vision Loss, Optic Nerve Tumors, Macular Edema, Von Hippel-Lindau Disease, VEGF, EYE001, VHL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- Mar 2003
- Study completion
- Nov 2005
- First posted
- 7 Mar 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the ability of the experimental drug EYE001 to reduce retinal thickening and improve vision in patients with Von Hippel-Lindau syndrome (VHL). Angiomas (blood vessel tumors) commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Although the tumors are not cancerous, they may cause significant vision loss. Current treatments, including laser therapy, cryotherapy, and vitrectomy, may not be successful or possible for all patients. EYE001 decreases production of VEGF, a growth factor that is important for the formation of new blood vessels and that is elevated in VHL. Preliminary findings from studies of other retinal diseases suggest that EYE001 can reduce retinal thickening and improve vision.
Patients 18 years of age and older with retinal angiomas due to VHL in one or both eyes and central vision loss of 20/40 or worse may be eligible for this study. Participants will undergo the following tests and procedures:
- Medical history, physical examination, electrocardiogram (EKG) and blood tests.
- Eye examination, including eye pressure measurement and dilation of the pupils to examine the retina.
- Fluorescein angiography to evaluate the eye's blood vessels. For this test, a yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures will reveal if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
- Optical coherence tomography to measure retinal thickness. The eyes are examined through a machine that produces cross-sectional pictures of the retina. These measures are repeated during the study to determine changes, if any, in retinal thickening.
- Electroretinogram (ERG) to measure electrical responses generated from within the retina. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside an open white globe that emits a series of light flashes for about 20 minutes. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Stereoscopic color fundus photography to examine the back of the eye. The pupils are dilated with eye drops to examine and photograph the back of the eye.
- EYE001 injections to treat ocular angiomas. Patients receive EYE001 injections through a needle into the eye's vitreous (gel-like substance that fills the inside of the eye). Six injections are given over a 30-week period. Before each injection, the surface of the eye is numbed with anesthetic eye drops. This is followed by injection of another anesthetic into the lower portion of they eye in the clear tissue surrounding the white of the eye. After a few minutes, the EYE001 is injected into the vitreous. Patients receive EYE001 injections at the first visit (during enrollment) and again at 6, 12, 18, 24, and 30 weeks after the first injection.
At each injection visit, participants repeat most of the tests described above to evaluate the response to treatment and return a week later for another eye examination. After the last injection, patients whose vision has improved may receive three more treatments at visits 36, 42, and 48. All participants will return for examinations at week 54 and at 2 months after their final injection.
Detailed description
Von Hippel-Lindau (VHL) 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. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of anti-VEGF therapy (EYE001) in 5 patients to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Patients will receive 6 intravitreal injections of study drug over a 30-week period, then return for a follow-up visit 1 year after initiating injections. The primary outcomes will be improvement in best corrected visual acuity of 15 letters or more at 1 year, reduction in retinal thickening and leakage at one year, changes in ERG amplitude and implicit time, and adverse events including local and systemic toxicities.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Patient must understand and sign the informed consent.
- Patient must be at least 18 years of age.
- Patient must have retinal angiomas secondary to VHL in one or both eyes.
- Patient must have either optic nerve tumors or peripheral tumors that have caused central vision loss of 20/40 or worse.
- Patient must have clear ocular media and adequate papillary dilation to permit good quality stereoscopic fundus photography.
Key exclusion criteria (6 listed)
- Significant media opacities, including cataract that precludes quality fundus photographs of the posterior pole.
- History or evidence of severe cardiac disease (electrocardiogram abnormalities, clinical history of unstable angina, acute coronary syndrome, myocardial infarction, revascularization procedure within 6 months prior to baseline, atrial or ventricular tachyarrythmias requiring ongoing treatment).
- History of stroke within 12 months of study entry.
- History of or current acute ocular or periocular infection (including any history of ocular herpes zoster).
- Any major surgical procedure within one month of study entry.
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 |
|---|---|---|
| EYE001 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7862955Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995 Mar;194(3):629-42. doi: 10.1148/radiology.194.3.7862955.
- Background: PubMed 11114638Libutti SK, Choyke PL, Alexander HR, Glenn G, Bartlett DL, Zbar B, Lubensky I, McKee SA, Maher ER, Linehan WM, Walther MM. Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease. Surgery. 2000 Dec;128(6):1022-7;discussion 1027-8. doi: 10.1067/msy.2000.110239.
- Background: PubMed 9145719Manski TJ, Heffner DK, Glenn GM, Patronas NJ, Pikus AT, Katz D, Lebovics R, Sledjeski K, Choyke PL, Zbar B, Linehan WM, Oldfield EH. Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. JAMA. 1997 May 14;277(18):1461-6. doi: 10.1001/jama.277.18.1461.
Related trials for Hippel-Lindau Disease
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EYE001 in people with Hippel-Lindau Disease, 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 10 inclusion and 6 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 4 Mar 2008. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00056199, which also lists 3 linked publications.
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 4 Mar 2008.