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

NCT02859441 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16015916-EI-0159
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Von Hippel-Lindau Syndrome

Keywords

Intravitreal Injection; Retinal Capillary Hemangioma

Outcome Measures

Primary Outcomes (1)

• Tabulation of Adverse Events

  The total number of adverse events through Week 52.

  From Baseline to Week 52

Secondary Outcomes (19)

• Tabulation of Adverse Events

  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))

  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])

  From Baseline to Week 104

• Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery

  From Baseline to Week 52

• Proportion of Participants Undergoing Ablative Treatment of RCH or Ocular Surgery

  From Baseline to Week 104

Study Arms (1)

E10030 and Ranibizumab

EXPERIMENTAL

Intravitreal injections of E10030 and Ranibizumab

Drug: Ranibizumab; Drug: E10030

Interventions

Ranibizumab DRUG

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.

E10030 and Ranibizumab

E10030 DRUG

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.

E10030 and Ranibizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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 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.
• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 34549489 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

von Hippel-Lindau Disease

Interventions

Ranibizumab; E10030 aptamer

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Henry E Wiley, M.D., Principal Investigator, NEI
• Organization: National Institutes of Health

wileyhe@nei.nih.gov

301-496-6583

Study Officials

• Henry E Wiley, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2016
• First Posted: August 9, 2016
• Study Start: January 23, 2017
• Primary Completion: July 9, 2019
• Study Completion: July 9, 2019
• Last Updated: November 1, 2021
• Results First Posted: July 14, 2020

Record last verified: 2019-07

Locations

US (1)