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

NCT01972438 | Terminated Phase 2 Results DMC

• 2 other identifiers: 13020613-EI-0206
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Some eye diseases can be helped by eye drops made from a person's own blood. These eye drops are called autologous serum eye drops, or ASEDs. ASEDs have been studied in only a few people with graft vs. host disease (GVHD) affecting the eye and were found to be helpful with few side effects. The purpose of this study was to determine whether ASEDs are safe and more effective than control (normal saline) and can help with eye symptoms in people with severe chronic eye GVHD. Each participant in this study was to have blood drawn to prepare ASEDs specifically for the participant. Each participant was scheduled to receive ASEDs for 3 months and placebo eye drops (salt water) for 3 months. Participants did not know when they were receiving the ASEDs and when they were receiving placebo eye drops.

Conditions

Graft vs Host Disease

Keywords

Graft Versus Host Disease; Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Experienced a ≥ 50% Reduction in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH/National Eye Institute (NEI) Visual Analogue Scale in the Study Eye From Baseline to Month 3.

  A ≥ 50% reduction in the combined score was considered a treatment success. While the design is a crossover study, the primary outcome was assessed after the first period at Month 3. Oxford punctate keratopathy is an objective measure from 0-5 (cornea only) and the NIH/NEI visual analogue scale is a subjective grading performed by the participant regarding his/her ocular dryness, redness and irritation (scored 0-3 for each symptom with 0 = none, 1 = mild, 2 = moderate and 3 = severe for a total score between 0-9). The combined score was a number between 0-14 with the higher number representing a worse outcome.

  Baseline and 3 months

Secondary Outcomes (22)

• Number of Systemic and Ocular Toxicities and Adverse Events

  Study Duration, up to 24 months

• Number of Participants Withdrawn From the Study Treatment Due to Vision Loss, Adverse Events or Treatment Failure

  Study Duration, up to 24 months

• Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Study Eye at 3 Months Compared to Baseline

  Baseline and 3 Months

• Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Fellow Eye at 3 Months Compared to Baseline

  Baseline and 3 Months

• Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Study Eye at 6 Months Compared to Baseline

  Baseline and 6 Months

Study Arms (2)

ASEDs - Saline

EXPERIMENTAL

Participants administer autologous serum eye drops (ASEDs) daily for the first three months, then crossover to administer control (normal saline) eye drops daily beginning at Month 3 through Month 6.

Drug: ASEDs; Drug: Saline

Saline - ASEDs

PLACEBO COMPARATOR

Participants administer control (normal saline) eye drops daily for the first three months, then crossover to administer autologous serum eye drops (ASEDs) daily beginning at Month 3 through Month 6.

Drug: ASEDs; Drug: Saline

Interventions

ASEDs DRUG

Experimental Intervention

ASEDs - Saline; Saline - ASEDs

Saline DRUG

Control Intervention

ASEDs - Saline; Saline - ASEDs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 years of age or older.
• Participant must understand and sign the protocol's informed consent document.
• Participant must have severe ocular Graft-versus-host Disease (GVHD) in one (unilateral) or both (bilateral) eyes with the following characteristics in the study eye:
• Combined score of modified Oxford punctate keratopathy grading and National Institutes of Health (NIH)/National Eye Institute (NEI) visual analogue scale of ≥ 4, and
• Composite assessment scale (CAS) score of ≥ 3, and
• Schirmer's tear test without anesthesia of ≤ 5 mm, and
• Not responsive to standard medical treatment for at least three months prior to randomization. Standard medical treatment includes cyclosporine (Restasis®) ophthalmic emulsion (if tolerated), steroid drops (unless contraindicated), lubricating drops and ointments.
• Participant is enrolled in an NIH study at the National Cancer Institute (NCI) or National Heart, Lung and Blood Institute (NHLBI).
• Participant is willing and able to supply an adequate amount of blood to create the autologous serum eye drops (ASEDs).

You may not qualify if:

• Participant is unable to comply with study procedures or follow-up visits.
• Participant is seropositive with positive nucleic acid confirmatory tests for human immunodeficiency virus-1/2 (HIV-1/2), human T lymphotropic virus-I/II (HTLV-I/II), hepatitis C virus (HCV), and/or hepatitis B virus (HBV) without confirmed history of vaccination.
• Participant has GVHD proliferative keratopathy, uveitis or GVHD retinopathy in either eye.
• Participant has an active ocular infection in either eye.
• Participant has an allergy to dilating or anesthetic eye drops.
• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• Yamada C, King KE, Ness PM. Autologous serum eyedrops: literature review and implications for transfusion medicine specialists. Transfusion. 2008 Jun;48(6):1245-55. doi: 10.1111/j.1537-2995.2008.01665.x. Epub 2008 Apr 10.

  PMID: 18410252 BACKGROUND

• Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003 Oct;22(7):640-50. doi: 10.1097/00003226-200310000-00008.

  PMID: 14508260 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Manuel B. Datiles, III, MD, Principal Investigator, NEI
• Organization: National Institutes of Health

DatilesM@nei.nih.gov

301-594-7052

Study Officials

• Manuel B Datiles, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: October 30, 2013
• Study Start: November 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: January 1, 2016
• Last Updated: December 8, 2016
• Results First Posted: September 13, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)