Safety and Preliminary Efficacy of IVMED-80 Eye Drops in Keratoconus Patients

NCT05241145 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IVNA 17-02
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

We investigated the use of a copper sulfate eye drop (IVMED-80) for the treatment of keratoconus. Preliminary laboratory data shows that the addition of copper sulfate increase crosslinking of the structural proteins of the cornea thereby halting the progressing corneal thinning and bulging seen in keratoconus. We conducted a Phase 1/2a study to evaluate the safety and preliminary efficacy of a 6-week and a 16-week regimen using IVMED-80 and studied its impact on ocular safety and the change/progression in patients' vision and clinical measurements.

Conditions

Keratoconus; Corneal Ectasia

Keywords

Keratoconus; Corneal Ectasia; Copper; Micronutrients; Eye drops; Topical Therapy

Outcome Measures

Primary Outcomes (3)

• Mean Maximum Central Keratometry (Kmax)

  Change in maximum central keratometry after the assigned treatment was compared with baseline measures. This will be evaluated with and without z-score imputation. It will also be evaluated with a linear mixed effects model.

  26 weeks

• Number of Treatment-Emergent Adverse Events

  Treatment-emergent adverse events (TEAEs) were defined as events requiring additional treatments or cessation of the study article for which the date of onset was on or after the date of first dose of double-masked study drug at Day 0.

  26 Weeks

• Mean Best Corrected Distance Visual Acuity (BCVA)

  Change in BCVA after the assigned treatment was compared with baseline measures.

  26 Weeks

Secondary Outcomes (14)

• Mean Corneal Astigmatism

  26 Weeks

• Mean Central Keratometry (Kmean)

  26 Weeks

• Mean Posterior Maximum Corneal Elevation

  26 Weeks

• Mean Endothelial Cell Count (ECC)

  26 Weeks

• Percentage of patients with discomfort and redness upon instillation

  26 Weeks

Study Arms (3)

IVMED-6Wk

EXPERIMENTAL

In Group 1 (IVMED-6Wk), patients instilled IVMED-80 eye drops into their study eye twice a day for 6 weeks and were followed for an additional 20 weeks without treatment (total 26 weeks)

Drug: IVMED-80

IVMED-16Wk

EXPERIMENTAL

In Group 2 (IVMED-16Wk), patients instilled IVMED-80 eye drops into their study eye twice a day for 16 weeks and were followed for an additional 10 weeks without treatment (total 26 weeks)

Drug: IVMED-80

Placebo

PLACEBO COMPARATOR

In Group 3 (Placebo), patients instilled IVMED-80 vehicle solution eye drops into their study eye twice a day for 16 weeks and were followed for an additional 10 weeks without treatment (total 26 weeks)

Other: Placebo

Interventions

IVMED-80 DRUG

Good Manufacturing Practices-grade copper (ІІ) sulfate pentahydrate (CuSO4 #5H2O MW 249.69) was dissolved in a vehicle solution comprised of a balanced salt solution (BSS) with osmolality of approximately 500 mOsm/L. Copper sulfate was concentrated to 0.15 mg/mL. The drops were manufactured on prior to the study at a compounding pharmacy in Salt Lake City, Utah.

IVMED-16Wk; IVMED-6Wk

Placebo OTHER

This was identical to the IVMED-80 product, but without the active ingredient, copper sulfate.

Also known as: IVMED-80 Vehicle

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Mild to moderate keratoconus and/or corneal ectasia post-LASIK or Photo-Refractive Keratectomy
• Age 18 to 40
• Minimum corneal thickness of \> 350 microns
• Maximum corneal keratometry of 45 D to 67 D
• Absence of systemic comorbidities that pose a significant surgical risk
• Absence of ocular comorbidities
• Willing and able to comply with clinic visits and study-related procedures.
• Provide signed informed consent

You may not qualify if:

• Significant central corneal scarring or hydrops
• Previous corneal surgeries
• Presence of pre-existing glaucoma, uveitis, uncontrolled diabetic retinopathy, or prior ocular trauma or prior intraocular surgery.
• Myopic degeneration with potential acuity less than 20/40 in the Study Eye.
• Down's Syndrome, retinitis pigmentosa, Ehlers-Danlos Syndrome, osteogenesis imperfecta (or other collagen disorder) or Anton's Syndrome.
• Prior retinal detachment involving the macula
• Received a sub-Tenon's injection of corticosteroid within the past 6 months, or any intravitreal injection within the past 6 months in the study eye prior to Visit 1
• Current use, or anticipated initiation during the study, of a systemic corticosteroid or an immunosuppressant agent by any route (oral, injectables)
• History or current condition of substance or alcohol abuse within the past year
• Participation in a clinical trial with use of any investigational drug or treatment within 30 days prior to Visit 1
• Employee of the study site or their immediate families.
• Pregnancy or planning to become pregnant.

Sponsors & Collaborators

• iVeena Delivery Systems, Inc.: lead
• Codet Vision Institute: collaborator

Study Sites (1)

Codet Vision Institute

Tijuana, Estado de Baja California, 22320, Mexico

Location

Related Publications (3)

• Olivares Jimenez JL, Guerrero Jurado JC, Bermudez Rodriguez FJ, Serrano Laborda D. Keratoconus: age of onset and natural history. Optom Vis Sci. 1997 Mar;74(3):147-51. doi: 10.1097/00006324-199703000-00025.

  PMID: 9159804 BACKGROUND

• Wagner H, Barr JT, Zadnik K. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date. Cont Lens Anterior Eye. 2007 Sep;30(4):223-32. doi: 10.1016/j.clae.2007.03.001. Epub 2007 May 3.

  PMID: 17481941 BACKGROUND

• Kymes SM, Walline JJ, Zadnik K, Sterling J, Gordon MO; Collaborative Longitudinal Evaluation of Keratoconus Study Group. Changes in the quality-of-life of people with keratoconus. Am J Ophthalmol. 2008 Apr;145(4):611-617. doi: 10.1016/j.ajo.2007.11.017. Epub 2008 Jan 28.

  PMID: 18226798 BACKGROUND

MeSH Terms

Conditions

Keratoconus

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Study Officials

• Arturo Chayet, MD

  Codet Vision Institute

  PRINCIPAL INVESTIGATOR

• Balamurali K. Ambati, MD, PhD

  iVeena Delivery Systems

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigational products, IVMED-80 or Placebo (IVMED-80 vehicle solution) eye drops, were masked to all sponsor and site personnel with the exception of those directly involved with the production, labeling and shipping of product to the study sites. During the study, the identity of the test articles and randomization were not revealed. An unmasked study coordinator managed test article receipt, dispensing and inventory at the study site. Investigators who interacted with study patients to assess safety and efficacy were masked as to the identity of the test articles and treatment group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study used a three-arm, parallel design. Eligible study patients were randomly assigned to 1 of 3 treatment group following a 1:1:1 schedule.

Study Record Dates

• First Submitted: February 5, 2022
• First Posted: February 15, 2022
• Study Start: February 8, 2019
• Primary Completion: July 8, 2020
• Study Completion: July 8, 2020
• Last Updated: February 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available pending journal publication time frames.
• Access Criteria: Data will be displayed in figures and tables and as supplemental files in the published journal and accessibility will depend on journal open access policies.

Locations

ME (1)