NCT02042027

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 17, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 22, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

August 5, 2016

Status Verified

August 1, 2016

Enrollment Period

2 years

First QC Date

January 17, 2014

Last Update Submit

August 3, 2016

Conditions

Corneal NeovascularizationCorneal Graft FailureAnterior Segment Inflammation

Keywords

corneal neovascularizationGamunex-CIVI-ganterior segment inflammation

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (12)

  • Ability to regress neovascularization and promote graft survival

    28 weeks after transplant

  • Ability to regress neovascularization and promote graft survival

    52 weeks after transplant

  • Need for immunosuppression

    week 28

  • Need for immunosuppression

    week 52

  • Effect on corneal infections

    week 28

  • +7 more secondary outcomes

Study Arms (2)

Group A

ACTIVE COMPARATOR

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

Group B

ACTIVE COMPARATOR

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

Interventions

Gamunex-CDRUG

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

Also known as: IVIg
Group AGroup B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

John A. Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (6)

  • 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.

    PMID: 22898649BACKGROUND

  • 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.

    PMID: 11507336BACKGROUND

  • 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.

    PMID: 22427553BACKGROUND

  • 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.

    PMID: 19194480BACKGROUND

  • 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.

    PMID: 17460257BACKGROUND

  • 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.

    PMID: 23464925BACKGROUND

MeSH Terms

Conditions

Corneal Neovascularization

Interventions

HizentraImmunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Corneal DiseasesEye DiseasesNeovascularization, PathologicMetaplasiaPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

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

    University of Utah

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Ophthalmology

Study Record Dates

First Submitted

January 17, 2014

First Posted

January 22, 2014

Study Start

July 1, 2014

Primary Completion

July 1, 2016

Study Completion

July 1, 2016

Last Updated

August 5, 2016

Record last verified: 2016-08

Locations

US(1)