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

Study Overview
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Brief Summary
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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.

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

Conditions
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Corneal Neovascularization, Corneal Graft Failure, Anterior Segment Inflammation

Intervention / Treatment
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* Drug: Gamunex-C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Candidates for corneal transplantation (only one eye per patient would be enrolled) 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 Patients with refractory anterior uveitis, non-responding corneal melts, or non-responding ocular cicatricial pemphigoid Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Age 18 or over Exclusion Criteria: 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 Patients with active corneal infection requiring additional treatment modalities Patients receiving coumadin with INR >2.0, other anti-thrombotic agents (e.g., aspirin, Plavix) permitted at discretion of investigator History of CVA or MI within 6 months prior to study enrollment Uncontrolled BP- defined as SBP>160 mmHg or DBP >95mmHg while patient is sitting Pregnant or breast-feeding women 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>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<br>* Patients will receive 50 mg (0.5 mL) subconjunctival Gamunex-C injection in addition to standard of care treatment (steroids and cyclosporine)<br>* Other names: IVIg;|
| Active Comparator: Group B<br>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<br>* Patients will receive 50 mg (0.5 mL) subconjunctival Gamunex-C injection in addition to standard of care treatment (steroids and cyclosporine)<br>* Other names: IVIg;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corneal neovascularization, Gamunex-C, IVI-g, anterior segment inflammation