Study for the Treatment of Ocular Chronic Graft-Versus-Host Disease (GVHD) With Amniotic Fluid Eye Drops (AFED)

Study Overview
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Brief Summary
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A Randomized, Double-blinded, Placebo-Controlled Study for the Treatment of Ocular Chronic Graft Verses Host Disease with Processed Amniotic Fluid (pAF) Drops.

Detailed Description
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This is a randomized (to each eye, within patient), double-blinded, placebo-controlled study of the efficacy of Processed Amniotic Fluid (pAF) in patients with hematologic malignancies who have undergone Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and are diagnosed with Chronic Graft Verses Host Disease of the eye.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled Study for the Treatment of Ocular Chronic Graft-Versus-Host Disease (GVHD) With Amniotic Fluid Eye Drops (AFED)

Conditions
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Ocular Graft Versus Host Disease

Intervention / Treatment
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* Biological: Amniotic Fluid Eye Drops (AFED)
* Other: Saline Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed within 5 years after hematopoietic stem cell transplant for any disease, with any graft and any conditioning regimen with at least one of the following symptoms: Dry eye symptoms partially affecting (requiring lubricant drops > 3 x per day or punctal plugs, or thermally cauterized puncta) or significantly affecting (special eyeware to relieve pain) activities of daily living (ADL) Unable to work because of ocular symptoms Loss of vision due to keratoconjunctivitis sicca (KCS) Patients may be using bilateral scleral lenses and/or bilateral punctal plugs at the time of accrual. Patients who are 18 years of age or older. Willing and able to provide informed consent. Exclusion Criteria: Patients who have any other reversible cause for dry eye at the time of accrual. More than 3 lines of therapy beyond corticosteroids with or without calcineurin inhibitors or sirolimus Relapsed malignancy after transplantation A difference in dryness between both eyes of more than 2 points of the grading provided by the International Dry Eye Workshop (DEWS) 2007 report Patients who are pregnant or plan to become pregnant while participating in the study. - Patients who are not willing to discontinue the use of any eye drops, with the exception of non-medicated lubricant eye drops (artificial tears). All eye drops (excluding non-medicated lubricant eye drops) must be stopped at least seven days before treatment with pAF. Inability to comply with the investigational plan and visit schedule for any

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amniotic Fluid Eye Drops (AFED) - All participants, One eye<br> | Biological: Amniotic Fluid Eye Drops (AFED)<br>* One drop (0.25 mL) in one eye twice daily for up to 3 months<br>|
| Placebo Comparator: Saline Solution - All participants, One eye<br> | Other: Saline Solution<br>* One drop (0.25 mL) in the other eye twice daily for up to 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Response is a composite of the NIH Consensus Conference (CC) for assessment of response in chronic GVHD (eye score) and the International Dry Eye Workshop (DEWS) grading scale. Responders would be defined as a one point improvement in the dry eye grading scale (DEWS), without worsening in the eye score. | 100 days | 
| Safety of pAF in patients with chronic ocular GVHD: CTCAE version 4 | Serious adverse events and ocular adverse events using CTCAE version 4 | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Assessment of Cancer Therapy: General (FACT-G) | Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much). | 30 days | 
| Functional Assessment of Cancer Therapy: General (FACT-G) | Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much). | 60 days | 
| Functional Assessment of Cancer Therapy: General (FACT-G) | Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much). | 100 days | 
| National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms). | 30 days | 
| National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms). | 60 days | 
| National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms). | 100 days | 
| Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading | Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score. | 30 days | 
| Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading | Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score. | 60 days | 
| Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading | Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score. | 100 days | 
| Pain Assessment | Change in patient reported pain level using 0-10 pain rating scale with zero being no pain to 10 being very severe pain. | 60 days | 
| Changes in Visual Acuity | Ophthalmologic assessment to determine changes in visual acuity related to the administration of pAF. | Up to 100 days | 
| Effects on the Corneal Surface | Ophthalmologic assessment to determine the effects of treatment with pAF on the corneal surface of patients with ocular chronic GVHD. | Up to 100 days |