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

Sponsor

University of Utah (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02042027

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Corneal Neovascularization Corneal Graft Failure Anterior Segment Inflammation	Drug: Gamunex-C	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Ability to regress neovascularization [at time of transplant]
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)

Secondary Outcome Measures

Ability to regress neovascularization and promote graft survival [28 weeks after transplant]
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)
Ability to regress neovascularization and promote graft survival [52 weeks after transplant]
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)
Need for immunosuppression [week 28]
need for immunosuppression at weeks 28 in both treatment groups
Need for immunosuppression [week 52]
need for immunosuppression at week 52 in both treatment groups
Effect on corneal infections [week 28]
Effect on corneal infections or other side effects through week 28 in both treatment groups
Effect on corneal infections [Week 52]
effect on corneal infections or other side effects through week 52 in both treatment groups
Visual outcome at week 28 [Week 28]
visual outcome (by ETDRS chart) at week 28 in both treatment groups
Visual outcome at week 52 [Week 52]
visual outcome (by ETDRS chart) at week 52 in both treatment groups
Mean number of injections through week 28 [week 28]
mean number of injections performed per patient through weeks 28
Mean number of injections through week 52 [week 52]
mean number of injections performed per patient through week 52 in patients receiving subconjunctival IVIg (Gamunex-C) injections
Need for rescue treatment in standard of care group [Week 28]
need for rescue treatment in the standard of care group through week 28
Need for rescue treatment in standard of care group [week 52]
need for rescue treatment in the standard of care group through week 52

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.