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

Corneal Neovascularization Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02042027
• Other study ID #: AMB70983
• Status: Withdrawn
• Phase: Phase 1
• First received: January 17, 2014
• Last updated: August 3, 2016
• Start date: July 2014
• Est. completion date: July 2016

Study information

• Verified date: August 2016
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anterior Segment Inflammation
• Corneal Graft Failure
• Corneal Neovascularization
• Inflammation
• Neovascularization, Pathologic

Intervention

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)

Locations

Country	Name	City	State
United States	John A. Moran Eye Center	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001 Aug;12(4):242-9. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Luo L, Zhang X, Hirano Y, Tyagi P, Barabás 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Need for immunosuppression	need for immunosuppression at weeks 28 in both treatment groups	week 28	No
Secondary	Need for immunosuppression	need for immunosuppression at week 52 in both treatment groups	week 52	No
Secondary	Effect on corneal infections	Effect on corneal infections or other side effects through week 28 in both treatment groups	week 28	No
Secondary	Effect on corneal infections	effect on corneal infections or other side effects through week 52 in both treatment groups	Week 52	No
Secondary	Visual outcome at week 28	visual outcome (by ETDRS chart) at week 28 in both treatment groups	Week 28	No
Secondary	Visual outcome at week 52	visual outcome (by ETDRS chart) at week 52 in both treatment groups	Week 52	No
Secondary	Mean number of injections through week 28	mean number of injections performed per patient through weeks 28	week 28	No
Secondary	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	No
Secondary	Need for rescue treatment in standard of care group	need for rescue treatment in the standard of care group through week 28	Week 28	Yes
Secondary	Need for rescue treatment in standard of care group	need for rescue treatment in the standard of care group through week 52	week 52	Yes