Evaluating Adjunctive Cryopreserved Amniotic Membrane Treatment in Herpes Simplex Dendritic Keratitis

A Pilot Study Evaluating Adjunctive Cryopreserved Amniotic Membrane Treatment for Primary or Recurrent Herpes Simplex Dendritic Keratitis

To prospectively evaluate the effectiveness of Prokera Slim in adults with primary or recurrent herpetic epithelial keratitis in terms of visual function, corneal opacity, time to resolution, cost of care, number of patient visits.

Study Overview

• Status: Withdrawn
• Conditions: Herpes Simplex Dendritic Keratitis
• Intervention / Treatment: Other: Standard of Care; Device: Prokera Slim

Detailed Description

Cryopreserved amniotic membrane (AM) contains anti-inflammatory, anti-scarring and antiangiogenic effects known in treating many ocular surface diseases. This notion is further strengthened by many studies showing that amniotic membrane can effectively control inflammation in HSV stromal keratitis in a murine model of HSV necrotizing keratitis and surgical application in ~7 human studies of epithelial and stromal HSV keratitis with or without an adjuvant antiviral therapy. More importantly, PROKERA SLIM in conjunction with oral acyclovir has been shown to facilitate the ease of early intervention to accelerate restoration in herpetic keratitis in 2 case series of 5 eyes. However, a formal prospective study has not been performed.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute, Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject (male or female) is at least 18 years of age.
2. The subject is presenting with primary or recurrent herpetic dendritic epithelial keratitis based on investigator judgement
3. The subject is presenting with acute (within 30 days) herpetic dendritic epithelial keratitis
4. The subject is willing to comply with all study procedures and is able to consent.

Exclusion Criteria:

1. Clinical signs of a cause other than herpes simplex virus
2. Presence of corneal ulcer with or without microbial infection
3. Lid surface abnormalities or conjunctival scarring that affect lid function in either eye
4. Atopic disease
5. History of penetrating keratoplasty
6. Active stromal keratitis or iritis
7. Presence of systemic or ocular infection or inflammation that is not related to herpes simplex virus (such as Sarcoidosis, Cogan syndrome, atopy, Lyme disease, Syphilis, mumps, Epstein-Barr virus)
8. Ocular surface malignancy
9. History of recent ocular surgery/trauma, which could affect corneal sensitivity, e.g., corneal transplantation, LASIK
10. A medical or ocular condition, or a personal situation, which in the principal investigator's opinion, is not appropriate for participation in the trial
11. Current enrollment in another interventional drug or device study or participation in such a study within 30 days of anticipated entry into this study
12. Not capable of providing informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Arm; All subjects enrolled in the study will receive the standard of care that includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID (four times daily) for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion).	Other: Standard of Care; Standard of care includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion).
Active Comparator: Treatment Arm; All subjects enrolled in the study will receive the standard of care that includes epithelial debridement of all dendrites via Weck-Cel Cellulose sponge, topical prophylactic antibiotics (e.g., Ocuflox QID for one week) and oral acyclovir (400 mg 5x/day for 10 days for primary cases but tapered to 2x/day for 3 months for recurrent cases based on investigator's discretion). The treatment arm will also receive the placement of PROKERA SLIM for 5-7 days. A second PROKERA SLIM may be applied based on investigator's discretion. For patients with bilateral involvement only the worse eye will be enrolled for the treatment arm.	Device: Prokera Slim; Placement of an Adjunctive Cryopreserved Amniotic Membrane Treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-dependent change in BCVA by 1 weeks	The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL).	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete epithelialization by 1 week	Proportion of patients with complete epithelialization by 1 week, graded 0, SPK 1+, SPK 2+, SPK 3+ (SPK is Superficial Punctate Keratitis)	1 week
Time-dependent change in BCVA by 2 weeks	The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL).	2 weeks
Time-dependent change in BCVA by 2 months	The BSCVA was recorded at 4 meters by a refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL).	2 months
Proportion of patients with corneal opacity at 2 months	Proportion of patients with corneal opacity at 2 months, graded 0, 1+, 2+, 3+, and 4+.	2 months
Proportion of patients with recurrence by 2 months	Proportion of patients with recurrence by 2 months counted individually	2 months
Change in corneal sensitivity from baseline to 2 months	Change in corneal sensitivity from baseline to 2 months using Cochet-Bonnet esthesiometer, graded 0/4, 1/4, 2/4, 3/4, and 4/4.	2 months
Change in conjunctival inflammation at 1 week	Conjunctival inflammation graded by investigator as none (0), mild (1), moderate (2), and severe (3)	1 week
Change in conjunctival inflammation at 2 week	Conjunctival inflammation graded by investigator as none (0), mild (1), moderate (2), and severe (3)	2 week
Total number of extra patient visits, treatments, and procedures throughout study	Total number of extra patient visits, treatments, and procedures throughout study, counted individually by type	2-3 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Tissue Tech Inc.
• Investigators: Principal Investigator: Richard Stutzman, M.D., Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2021
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Actual): July 28, 2022

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Prokera; Adjunctive Cryopreserved Amniotic Membrane; Prokera Slim
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Eye Diseases; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Corneal Diseases; Herpesviridae Infections; Eye Infections; Eye Infections, Viral; Keratitis, Herpetic; Keratitis; Herpes Simplex; Keratitis, Dendritic
• Other Study ID Numbers: IRB00021203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Share EPD once available
• IPD Sharing Time Frame: 1 year
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes