A Randomized, Controlled, Double-masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients



Status:Suspended
Conditions:Orthopedic, Hematology
Therapuetic Areas:Hematology, Orthopedics / Podiatry
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:September 2013
End Date:December 2016

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A Randomized, Controlled, Double-Masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-Host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients

Objective:

A common, serious and debilitating long term complication of hematopoietic stem cell
transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to
85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and
cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival
and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have
been used, such as various lubricating agents, steroid drops and ointments, cyclosporin
drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none
offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision
associated with ocular GVHD. An alternative treatment that has previously been safely
investigated is autologous serum eye drops (ASEDs). The objective of this study is to
determine whether ASEDs are more effective than control (normal saline) in the treatment of
severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment.

Study Population:

Eighteen post-HSCT patients with severe ocular GVHD unresponsive to standard medical
treatment are enrolled. Initially, 34 post-HSCT patients with severe ocular GVHD
unresponsive to standard medical treatment were to be enrolled. However, only 18 are
enrolled, as the IP will no longer be provided to participants.

Design: This is a Phase 2, randomized, double-masked, controlled, crossover, single-center
study to investigate ASEDs in participants with severe chronic ocular GVHD. During the
initial crossover phase of the study, participants participated in a two-period, six-month,
crossover study in which participants were randomized to one of two treatment sequence
groups. The two groups were: 1) daily administration of ASEDs for the first three months and
then crossover to control (normal saline) eye drops beginning at Month 3 through Month 6, or
2) daily administration of control (normal saline) eye drops for the first three months and
then crossover to ASEDs beginning at Month 3 through Month 6. Participants in both groups
applied the assigned drops four times per day for six months, as well as maintain their
current standard ocular GVHD therapy. Following the initial crossover phase, beginning at
the Month 6 visit, participants were provided ASEDs as open-label treatment on an as-needed
basis until study completion. The participants were informed to discontinue use of the IP
and send it back the NIH Pharmacy. During the first year, required clinic visits occurred at
Baseline, Months 3, 6 and 12 with required telephone follow-up visits at Months 7 and 9.
Following the Month 12 visit, participants were evaluated every six months, alternating
telephone follow-up visits with clinic visits, until the last enrolled participant reaches
his/her Month 12 visit. All study participants will now be scheduled for a final safety
visit. At the discretion of the Investigator, participants who have not completed the Month
12 visit may have the most recent study visit constitute as the final safety visit,
otherwise the participant will be scheduled for a final safety visit within 4 1/2 months.
Participants who have already surpassed the Month 12 visit will be scheduled for a final
safety visit within 4 1/2 months.

Outcome Measures:

The primary outcome is the proportion of participants experiencing a

greater than or equal to 50% reduction in the combined score of the modified Oxford punctate
keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to
Month 3. A greater than or equal to 50% reduction in the combined score will be considered a
treatment success. While the design is a crossover study, the primary outcome is assessed
after the first period at Month 3. Secondary outcomes include changes in the combined score
of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in
both eyes from baseline to the end of each period, changes in the chronic ocular GVHD
Composite Assessment Scale (CAS) score, objective testing, subjective testing and global
chronic GVHD assessments in both eyes. Safety outcomes will be the number and severity of
systemic and ocular toxicities and adverse events. The number of participants withdrawn from
the study treatment due to vision loss, adverse events or treatment failure will also
contribute to the assessment of safety.

Objective:

A common, serious and debilitating long term complication of hematopoietic stem cell
transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to
85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and
cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival
and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have
been used, such as various lubricating agents, steroid drops and ointments, cyclosporin
drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none
offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision
associated with ocular GVHD. An alternative treatment that has previously been safely
investigated is autologous serum eye drops (ASEDs). The objective of this study is to
determine whether ASEDs are more effective than control (normal saline) in the treatment of
severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment.

Study Population:

Eighteen post-HSCT patients with severe ocular GVHD unresponsive to standard medical
treatment are enrolled. Initially, 34 post-HSCT patients with severe ocular GVHD
unresponsive to standard medical treatment were to be enrolled. However, only 18 are
enrolled, as the IP will no longer be provided to participants.

Design:

This is a Phase 2, randomized, double-masked, controlled, crossover, single-center study to
investigate ASEDs in participants with severe chronic ocular GVHD. During the initial
crossover phase of the study, participants participated in a two-period, six-month,
crossover study in which participants were randomized to one of two treatment sequence
groups. The two groups were: 1) daily administration of ASEDs for the first three months and
then crossover to control (normal saline) eye drops beginning at Month 3 through Month 6, or
2) daily administration of control (normal saline) eye drops for the first three months and
then crossover to ASEDs beginning at Month 3 through Month 6. Participants in both groups
applied the assigned drops four times per day for six months, as well as maintain their
current standard ocular GVHD therapy. Following the initial crossover phase, beginning at
the Month 6 visit, participants were provided ASEDs as open-label treatment on an as-needed
basis until study completion. The participants were informed to discontinue use of the IP
and send it back the NIH Pharmacy. During the first year, required clinic visits occurred at
Baseline, Months 3, 6 and 12 with required telephone follow-up visits at Months 7 and 9.
Following the Month 12 visit, participants were evaluated every six months, alternating
telephone follow-up visits with clinic visits, until the last enrolled participant reaches
his/her Month 12 visit. All study participants will now be scheduled for a final safety
visit. At the discretion of the Investigator, participants who have not completed the Month
12 visit may have the most recent study visit constitute as the final safety visit,
otherwise the participant will be scheduled for a final safety visit within 4 1/2 months.
Participants who have already surpassed the Month 12 visit will be scheduled for a final
safety visit within 4 1/2 months.

Outcome Measures:

The primary outcome is the proportion of participants experiencing a

greater than or equal to 50% reduction in the combined score of the modified Oxford punctate
keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to
Month 3. A greater than or equal to 50% reduction in the combined score will be considered a
treatment success. While the design is a crossover study, the primary outcome is assessed
after the first period at Month 3. Secondary outcomes include changes in the combined score
of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in
both eyes from baseline to the end of each period, changes in the chronic ocular GVHD
Composite Assessment Scale (CAS) score, objective testing, subjective testing and global
chronic GVHD assessments in both eyes. Safety outcomes will be the number and severity of
systemic and ocular toxicities and adverse events. The number of participants withdrawn from
the study treatment due to vision loss, adverse events or treatment failure will also
contribute to the assessment of safety.

- INCLUSION CRITERIA:

1. Participant must be 18 years of age or older.

2. Participant must understand and sign the protocol s informed consent document.

3. Participant must have severe ocular GVHD in one (unilateral) or both (bilateral)
eyes with the following characteristics in the study eye:

1. Combined score of modified Oxford punctate keratopathy grading and NIH/NEI
visual analogue scale of greater than or equal to 4, and

2. Composite assessment scale score of greater than or equal 3, and

3. Schirmer s tear test without anesthesia of less than or equal to 5 mm, and

4. Not responsive to standard medical treatment for at least three months
prior to randomization. Standard medical treatment includes cyclosporine
(Restasis[R]) ophthalmic emulsion (if tolerated), steroid drops (unless
contraindicated), lubricating drops and ointments.

4. Participant is enrolled in an NIH study at the NCI or NHLBI.

5. Participant is willing and able to supply an adequate amount of blood to create
the ASEDs.

EXCLUSION CRITERIA:

1. Participant is unable to comply with study procedures or follow-up visits.

2. Participant is seropositive with positive nucleic acid confirmatory tests for HIV-12,
HTLV-I/II, HCV, and/or HBV without confirmed history of vaccination.

3. Participant has GVHD proliferative keratopathy, uveitis or GVHD retinopathy in either
eye.

4. Participant has an active ocular infection in either eye.

5. Participant has an allergy to dilating or anesthetic eye drops.

6. Participant has used Boston Scleral Lens (or similar lenses) in either eye or has
used ASEDs in either eye within the past two months. Participants who have used the
Boston Scleral Lens (or similar lenses) or ASEDs in either eye who did not respond to
treatment and have stopped using them for at least two months are eligible.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
?
mi
from
Bethesda, MD
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