Subconjunctival IVIg (Gamunex-C) Injection for Corneal Neovascularization and Inflammatory Conditions

The purpose of the study is to test the investigational drug Gamunex-C on the growth of blood vessels over the cornea. This study is being conducted by Dr. Balamurali Ambati at the Moran Eye Center at the University of Utah.

The cornea is the clear outer front part of the eye. In corneal neovascularization, blood vessels grow over the cornea. Corneal neovascularization and ocular anterior segment inflammations are sight-threatening conditions. Lipid deposition and edema with subsequent scar formation can compromise corneal clarity irreversibly. Corneal neovascularization is also a well recognized risk factor for corneal graft failure. In its natural state, the cornea is a site of immune privilege well suited to tissue transplantation. Once vascularized, there is direct exposure of corneal antigens to circulating host immune mechanisms greatly increasing the chance of rejection [Collaborative Corneal Transplantation Study].

Melting or inflammation in the anterior chamber, cornea, or ocular surface can cause irreversible scarring or destruction of the optical elements of the eye, which can compromise vision.

Current standard of care for such conditions includes use of topical steroids and sometimes immunosuppressants (e.g., cyclosporine). These do not address a common underlying corneal neovascularization or melting.

This is a Phase 1 clinical trial of subconjunctival IVIg (Gamunex-C) injection for treatment of corneal neovascularization in the setting of corneal transplantation with neovascularization. Candidates for corneal transplantation with corneal neovascularization in one or more quadrants crossing more than 0.5mm over the limbus will be identified for inclusion in our study.

Study Overview

• Status: Withdrawn
• Conditions: Corneal Neovascularization; Corneal Graft Failure; Anterior Segment Inflammation
• Intervention / Treatment: Drug: Gamunex-C

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • John A. Moran Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Candidates for corneal transplantation (only one eye per patient would be enrolled)
2. Patients with corneal neovascularization in one or more quadrants crossing more than 1.0 mm over the limbus at time of enrollment in the study
3. Patients with refractory anterior uveitis, non-responding corneal melts, or non-responding ocular cicatricial pemphigoid
4. Willing and able to comply with clinic visits and study-related procedures
5. Provide signed informed consent
6. Age 18 or over

Exclusion Criteria:

1. Patients receiving antiangiogenic anti-VEGF medication either systemically or intravitreally for other pathology or who have received these drugs within 3 months of study enrollment
2. Patients with active corneal infection requiring additional treatment modalities
3. Patients receiving coumadin with INR >2.0, other anti-thrombotic agents (e.g., aspirin, Plavix) permitted at discretion of investigator
4. History of CVA or MI within 6 months prior to study enrollment
5. Uncontrolled BP- defined as SBP>160 mmHg or DBP >95mmHg while patient is sitting
6. Pregnant or breast-feeding women
7. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Gamunex-C 50 mg subconjunctival injections, in addition to standard of care treatment (steroids and cyclosporine). One dose of Gamunex-C injection delivered four weeks prior to corneal transplant surgery and one dose at the time of corneal transplantation. Dose to be repeated if recurrence of corneal neovascularization	Drug: Gamunex-C; Patients will receive 50 mg (0.5 mL) subconjunctival Gamunex-C injection in addition to standard of care treatment (steroids and cyclosporine); Other Names: IVIg
Active Comparator: Group B; Gamunex-C 50 mg subconjunctival injections, one dose injected for patients with active disease from corneal melts (peripheral ulcerative keratitis; Mooren's ulcer), ocular cicatricial pemphigoid, or anterior uveitis refractory to conventional therapy.	Drug: Gamunex-C; Patients will receive 50 mg (0.5 mL) subconjunctival Gamunex-C injection in addition to standard of care treatment (steroids and cyclosporine); Other Names: IVIg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to regress neovascularization	Ability of subconjunctival IVIg (Gamunex-C) injection to regress neovascularization and promote graft survival after corneal transplantation, or retard corneal/anterior segment inflammation in patients with progressive/refractory conditions (corneal melts, ocular cicatricial pemphigoid, or refractory anterior uveitis)	at time of transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to regress neovascularization and promote graft survival	ability of subconjunctival IVIg (Gamunex-C) injection to regress neovascularization and promote graft survival after corneal transplantation, or retard corneal/anterior segment inflammation in patients with progressive/refractory conditions (corneal melts, ocular cicatricial pemphigoid, or refractory anterior uveitis)	28 weeks after transplant
Ability to regress neovascularization and promote graft survival	ability of subconjunctival IVIg (Gamunex-C) injection to regress neovascularization and promote graft survival after corneal transplantation, or retard corneal/anterior segment inflammation in patients with progressive/refractory conditions (corneal melts, ocular cicatricial pemphigoid, or refractory anterior uveitis)	52 weeks after transplant
Need for immunosuppression	need for immunosuppression at weeks 28 in both treatment groups	week 28
Need for immunosuppression	need for immunosuppression at week 52 in both treatment groups	week 52
Effect on corneal infections	Effect on corneal infections or other side effects through week 28 in both treatment groups	week 28
Effect on corneal infections	effect on corneal infections or other side effects through week 52 in both treatment groups	Week 52
Visual outcome at week 28	visual outcome (by ETDRS chart) at week 28 in both treatment groups	Week 28
Visual outcome at week 52	visual outcome (by ETDRS chart) at week 52 in both treatment groups	Week 52
Mean number of injections through week 28	mean number of injections performed per patient through weeks 28	week 28
Mean number of injections through week 52	mean number of injections performed per patient through week 52 in patients receiving subconjunctival IVIg (Gamunex-C) injections	week 52
Need for rescue treatment in standard of care group	need for rescue treatment in the standard of care group through week 28	Week 28
Need for rescue treatment in standard of care group	need for rescue treatment in the standard of care group through week 52	week 52

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Balamurali K Ambati, M.D., Ph.D., M.B.A., University of Utah

Publications and helpful links

General Publications

• Chang JH, Garg NK, Lunde E, Han KY, Jain S, Azar DT. Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol. 2012 Sep;57(5):415-29. doi: 10.1016/j.survophthal.2012.01.007.
• Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001 Aug;12(4):242-9. doi: 10.1097/00055735-200108000-00002.
• Cho YK, Uehara H, Young JR, Tyagi P, Kompella UB, Zhang X, Luo L, Singh N, Archer B, Ambati BK. Flt23k nanoparticles offer additive benefit in graft survival and anti-angiogenic effects when combined with triamcinolone. Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2328-36. doi: 10.1167/iovs.11-8393.
• Singh SR, Grossniklaus HE, Kang SJ, Edelhauser HF, Ambati BK, Kompella UB. Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. Gene Ther. 2009 May;16(5):645-59. doi: 10.1038/gt.2008.185. Epub 2009 Feb 5.
• Jani PD, Singh N, Jenkins C, Raghava S, Mo Y, Amin S, Kompella UB, Ambati BK. Nanoparticles sustain expression of Flt intraceptors in the cornea and inhibit injury-induced corneal angiogenesis. Invest Ophthalmol Vis Sci. 2007 May;48(5):2030-6. doi: 10.1167/iovs.06-0853.
• Luo L, Zhang X, Hirano Y, Tyagi P, Barabas P, Uehara H, Miya TR, Singh N, Archer B, Qazi Y, Jackman K, Das SK, Olsen T, Chennamaneni SR, Stagg BC, Ahmed F, Emerson L, Zygmunt K, Whitaker R, Mamalis C, Huang W, Gao G, Srinivas SP, Krizaj D, Baffi J, Ambati J, Kompella UB, Ambati BK. Targeted intraceptor nanoparticle therapy reduces angiogenesis and fibrosis in primate and murine macular degeneration. ACS Nano. 2013 Apr 23;7(4):3264-75. doi: 10.1021/nn305958y. Epub 2013 Mar 20.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimate): January 22, 2014

Study Record Updates

• Last Update Posted (Estimate): August 5, 2016
• Last Update Submitted That Met QC Criteria: August 3, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: corneal neovascularization; Gamunex-C; IVI-g; anterior segment inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Corneal Diseases; Metaplasia; Inflammation; Neovascularization, Pathologic; Corneal Neovascularization; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: AMB70983