Ocular Graft Versus Host Disease
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALAmniotic Fluid Eye Drops (AFED)
One drop (0.25 mL) in one eye twice daily for up to 3 months
OTHERSaline Solution
One drop (0.25 mL) in the other eye twice daily for up to 3 months
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. 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) 2. Unable to work because of ocular symptoms 3. 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 at time of accrual after the most recent 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 reason, in the judgement of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 60 Days | baseline and 60 days | Change in Quality of Life questionnaire from baseline to 60 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life. |
| Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 100 Days | baseline and 100 days | Change in Quality of Life questionnaire from baseline to 100 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life. |
| Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 30 Days | baseline and 30 days | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms) from baseline to 30 days. |
| Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 60 Days | baseline and 60 days | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms). |
| Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 100 Days | baseline and 100 days | Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms). |
| Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 30 Days | baseline and 30 days | Change in Quality of Life questionnaire from baseline to 30 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life. |
| Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 60 Days | baseline and 60 days | 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. |
| Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 100 Days | baseline and 100 days | 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. |
| Change in Pain Assessment From Baseline to 60 Days | baseline and 60 days | Change in patient reported pain level per treatment eye using 0-10 pain rating scale with zero being no pain to 10 being very severe pain. Each individual pain score was used to estimate a regression slope for each eye with pain as the outcome and day of pAF treatments as the explanatory variable. |
| Changes in Visual Acuity | baseline, 30 days, 60 days, and 100 days | Ophthalmologic assessment to determine changes in visual acuity related to the administration of pAF. |
| Effects on the Corneal Surface | Up to 100 days | Ophthalmologic assessment to determine the effects of treatment with pAF on the corneal surface of patients with ocular chronic GVHD. |
| Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline to 30 Days | baseline and 30 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Subjects received both Amniotic Fluid Eye Drops and Saline Solution. Each were randomized to one eye.
Amniotic Fluid Eye Drops (AFED): One drop (0.25 mL) in one eye twice daily for up to 3 months Saline Solution: One drop (0.25 mL) in the other eye twice daily for up to 3 months | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 61 years |
| Baseline Functional Assessment of Cancer Therapy - General (FACT-G) Score | 88 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
| Subject wears contacts (scleral lenses) | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 3 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Overall Response Rate | 3 eyes |
| Saline Solution - All Participants, One Eye | Overall Response Rate | 6 eyes |
p-value: 0.375McNemar
Secondary
Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 100 Days
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.
Time frame: baseline and 100 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 100 Days | Better results for pAF eye vs Placebo eye | 1 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 100 Days | Better results for Placebo eye vs pAF eye | 5 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 100 Days | Same Directional Results for Both Eyes | 7 Participants |
p-value: 0.156Wilcoxon (Mann-Whitney)
Secondary
Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 60 Days
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.
Time frame: baseline and 60 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 60 Days | Better results for pAF eye vs Placebo eye | 0 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 60 Days | Better results for Placebo eye vs pAF eye | 8 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline and 60 Days | Same Directional Results for Both eyes | 6 Participants |
p-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline to 30 Days
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.
Time frame: baseline and 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline to 30 Days | Better results for pAF eye vs Placebo eye | 3 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline to 30 Days | Better results for Placebo eye vs pAF eye | 5 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading From Baseline to 30 Days | Same Directional Results for Both Eyes | 5 Participants |
p-value: 0.563Wilcoxon (Mann-Whitney)
Secondary
Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 100 Days
Change in Quality of Life questionnaire from baseline to 100 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life.
Time frame: baseline and 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 100 Days | 3.0 score on a scale |
p-value: 0.445Wilcoxon (Mann-Whitney)
Secondary
Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 30 Days
Change in Quality of Life questionnaire from baseline to 30 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life.
Time frame: baseline and 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 30 Days | -1 Change in score on a scale |
p-value: 0.391Wilcoxon (Mann-Whitney)
Secondary
Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 60 Days
Change in Quality of Life questionnaire from baseline to 60 days. FACT-G is a combination score of physical, social/family, emotional, and functional well-being. The score ranges from 0 to 108. The higher the score, the better the quality of life.
Time frame: baseline and 60 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Functional Assessment of Cancer Therapy: General (FACT-G) From Baseline to 60 Days | 2.8 score on a scale |
p-value: 0.267Wilcoxon (Mann-Whitney)
Secondary
Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 100 Days
Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).
Time frame: baseline and 100 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 100 Days | Better results for pAF eye vs Placeob eye | 2 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 100 Days | Better results for Placebo eye vs pAF eye | 0 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 100 Days | Same Directional Results for Both Eyes | 13 Participants |
p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 30 Days
Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms) from baseline to 30 days.
Time frame: baseline and 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 30 Days | Better results for pAF eye vs Placebo eye | 3 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 30 Days | Better results for Placebo eye vs pAF eye | 0 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 30 Days | Same Directional Results for Both Eyes | 10 Participants |
p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 60 Days
Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).
Time frame: baseline and 60 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 60 Days | Better results for pAF eye vs. Placebo eye | 1 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 60 Days | Better results for Placebo eye vs pAF eye | 0 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in National Institutes of Health (NIH) Consensus Criteria (CC) Ocular Score of Chronic GVHD From Baseline to 60 Days | Same Directional Results for Both Eyes | 14 Participants |
p-value: <1Wilcoxon (Mann-Whitney)
Secondary
Change in Pain Assessment From Baseline to 60 Days
Change in patient reported pain level per treatment eye using 0-10 pain rating scale with zero being no pain to 10 being very severe pain. Each individual pain score was used to estimate a regression slope for each eye with pain as the outcome and day of pAF treatments as the explanatory variable.
Time frame: baseline and 60 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Change in Pain Assessment From Baseline to 60 Days | -0.004 regression slope |
| Saline Solution - All Participants, One Eye | Change in Pain Assessment From Baseline to 60 Days | -0.010 regression slope |
p-value: 0.208Wilcoxon (Mann-Whitney)
Secondary
Changes in Visual Acuity
Ophthalmologic assessment to determine changes in visual acuity related to the administration of pAF.
Time frame: baseline, 30 days, 60 days, and 100 days
Population: One participant at the 30 day and 100 day visit did not complete visual acuity assessments.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 30 days | Better results for pAF eye vs Placebo eye | 5 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 30 days | Better results for Placebo eye vs pAF eye | 2 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 30 days | Same directional results for both eyes | 6 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 60 days | Better results for pAF eye vs Placebo eye | 2 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 60 days | Better results for Placebo eye vs pAF eye | 5 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 60 days | Same directional results for both eyes | 7 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 100 days | Better results for pAF eye vs Placebo eye | 3 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 100 days | Better results for Placebo eye vs pAF eye | 2 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Changes in Visual Acuity | Change from baseline to 100 days | Same directional results for both eyes | 8 Participants |
p-value: 0.594Wilcoxon (Mann-Whitney)
p-value: 0.469Wilcoxon (Mann-Whitney)
p-value: 0.75Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Up to 100 days
Population: A participant missed the 30 day visit and another missed the 100 day visit.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 30 day visit | Better results for Placebo eye vs pAF eye | 7 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 30 day visit | Same directional results for both eyes | 5 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 30 day visit | Better results for pAF eye vs Placebo eye | 1 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 60 day visit | Better results for pAF eye vs Placebo eye | 3 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 60 day visit | Better results for Placebo eye vs pAF eye | 4 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 60 day visit | Same directional results for both eyes | 7 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 100 day visit | Better results for pAF eye vs Placebo eye | 0 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 100 day visit | Better results for Placebo eye vs pAF eye | 3 Participants |
| Amniotic Fluid Eye Drops (AFED) - All Participants, One Eye | Effects on the Corneal Surface | 100 day visit | Same directional results for both eyes | 10 Participants |
p-value: 0.063Wilcoxon (Mann-Whitney)
p-value: <1Wilcoxon (Mann-Whitney)
p-value: 0.25Wilcoxon (Mann-Whitney)