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

Primary Purpose

Corneal Neovascularization, Corneal Graft Failure, Anterior Segment Inflammation

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Gamunex-C

About this trial

This is an interventional treatment trial for Corneal Neovascularization focused on measuring corneal neovascularization, Gamunex-C, IVI-g, anterior segment inflammation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

John A. Moran Eye Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Group A

Group B

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

Ability to regress neovascularization and promote graft survival

Need for immunosuppression

need for immunosuppression at weeks 28 in both treatment groups

Need for immunosuppression

need for immunosuppression at week 52 in both treatment groups

Effect on corneal infections

Effect on corneal infections or other side effects through week 28 in both treatment groups

Effect on corneal infections

effect on corneal infections or other side effects through week 52 in both treatment groups

Visual outcome at week 28

visual outcome (by ETDRS chart) at week 28 in both treatment groups

Visual outcome at week 52

visual outcome (by ETDRS chart) at week 52 in both treatment groups

Mean number of injections through week 28

mean number of injections performed per patient through weeks 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

Need for rescue treatment in standard of care group

need for rescue treatment in the standard of care group through week 28

Need for rescue treatment in standard of care group

need for rescue treatment in the standard of care group through week 52

Full Information

NCT ID

NCT02042027

First Posted

January 17, 2014

Last Updated

August 3, 2016

Sponsor

University of Utah

1. Study Identification

Unique Protocol Identification Number

NCT02042027

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Withdrawn

Why Stopped

No participants enrolled

Study Start Date

July 2014 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Utah

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Corneal Neovascularization, Corneal Graft Failure, Anterior Segment Inflammation

Keywords

corneal neovascularization, Gamunex-C, IVI-g, anterior segment inflammation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Active Comparator

Arm Description

Arm Title

Group B

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gamunex-C

Other Intervention Name(s)

IVIg

Intervention Description

Patients will receive 50 mg (0.5 mL) subconjunctival Gamunex-C injection in addition to standard of care treatment (steroids and cyclosporine)

Primary Outcome Measure Information:

Title

Ability to regress neovascularization

Description

Time Frame

at time of transplant

Secondary Outcome Measure Information:

Title

Ability to regress neovascularization and promote graft survival

Description

Time Frame

28 weeks after transplant

Title

Ability to regress neovascularization and promote graft survival

Description

Time Frame

52 weeks after transplant

Title

Need for immunosuppression

Description

need for immunosuppression at weeks 28 in both treatment groups

Time Frame

week 28

Title

Need for immunosuppression

Description

need for immunosuppression at week 52 in both treatment groups

Time Frame

week 52

Title

Effect on corneal infections

Description

Effect on corneal infections or other side effects through week 28 in both treatment groups

Time Frame

week 28

Title

Effect on corneal infections

Description

effect on corneal infections or other side effects through week 52 in both treatment groups

Time Frame

Week 52

Title

Visual outcome at week 28

Description

visual outcome (by ETDRS chart) at week 28 in both treatment groups

Time Frame

Week 28

Title

Visual outcome at week 52

Description

visual outcome (by ETDRS chart) at week 52 in both treatment groups

Time Frame

Week 52

Title

Mean number of injections through week 28

Description

mean number of injections performed per patient through weeks 28

Time Frame

week 28

Title

Mean number of injections through week 52

Description

mean number of injections performed per patient through week 52 in patients receiving subconjunctival IVIg (Gamunex-C) injections

Time Frame

week 52

Title

Need for rescue treatment in standard of care group

Description

need for rescue treatment in the standard of care group through week 28

Time Frame

Week 28

Title

Need for rescue treatment in standard of care group

Description

need for rescue treatment in the standard of care group through week 52

Time Frame

week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Balamurali K Ambati, M.D., Ph.D., M.B.A.

Organizational Affiliation

University of Utah

Official's Role

Principal Investigator

Facility Information:

Facility Name

John A. Moran Eye Center

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22898649

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.

Results Reference

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PubMed Identifier

11507336

Citation

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.

Results Reference

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PubMed Identifier

22427553

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.

Results Reference

background

PubMed Identifier

19194480

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.

Results Reference

background

PubMed Identifier

17460257

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. doi: 10.1167/iovs.06-0853.

Results Reference

background

PubMed Identifier

23464925

Citation

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.

Results Reference

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

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