Treatment Safety and Efficacy of Pro-ocular™ 1% for Chronic Ocular Graft Following Allogeneic HSCT.

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of Pro-ocular™ 1% topical gel administered twice daily for 70 days in reducing or eliminating symptoms and signs of chronic ocular GvHD.

Detailed Description
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Ocular graft versus host disease presents a most severe form of ocular surface disease that compromises quality of life of afflicted allogeneic hematopoietic transplantation patients. A controlled study is necessary to verify findings obtained to date in isolated patients. Currently available ophthalmic solutions and suspensions, drugs and devices largely have not been effective in alleviating the suffering of chronic ocular GvHD patients. Thus, this is an unmet need that Pro-ocular™ topical gel can fulfill. Potential benefits: Decrease or cessation of adverse ocular symptoms and signs of chronic ocular GvHD, reduction or elimination of the need for other topical ocular therapeutic treatments for chronic ocular GvHD, and restoration of quality of life.

Official Title
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Treatment Safety and Efficacy Using Pro-ocular™ 1% for Chronic Ocular Graft-versus-host Disease (GvHD) Following Allogeneic Hematopoietic Stem Cell Transplantation.

Conditions
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Chronic Ocular Graft-versus-host Disease

Intervention / Treatment
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* Drug: Pro-ocular™ topical gel
* Drug: Placebo topical gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of any race, at least 18 years of age at Visit 1 Screening. Has the diagnosis of chronic ocular GvHD. Has an NIH Consensus Eye Score of at least 2. On the GLIA Ocular Surface Disease Symptoms Questionnaire at Screening, has ocular discomfort at a severity score of moderate or more, and at least one other symptom at a severity of moderate or more. One or more signs from the list of chronic ocular GvHD signs below Has provided verbal and written informed consent. Be able and willing to follow oral and written instructions, including participation in all study assessments and visits. Exclusion Criteria: Wearing scleral or contact lenses within the last month, or those who plan to start wearing scleral or contact lenses during the study. Anticipate major changes in systemic GvHD management during study period. Comorbidity with other severe or chronic eye conditions that in the judgment of the investigator will interfere with study assessments, such as but not limited to retinal detachment, recent ocular surgery, Bell's palsy, active trigeminal neuritis or trigeminal neuralgia. Anticipate change of vision correction or anticipate any ocular procedures during study period. A woman who is pregnant, nursing an infant, or planning a pregnancy. A woman of childbearing potential who has a positive urine pregnancy test at Visit 1, or who does not use an adequate method of birth control throughout the study period. Has a known adverse reaction and/or sensitivity to the study drug or its components. Unwilling to cease the use of sunscreen on the forehead or eye area. Intraocular pressure >22 mm Hg at screening visit with or without ongoing glaucoma treatment. Currently enrolled in an investigational drug or device study for chronic ocular GvHD.

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
Interventional Model Description: The double-masked phase involves placebo controlled administration of study drug for 70 days or 10 weeks. Subsequently the placebo group will receive the active study drug of 42 days or 6 weeks. Long term open label phase to 27 months.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pro-ocular™<br>Pro-ocular™ 1% topical gel applied dermally to forehead twice daily, morning and before bedtime. | Drug: Pro-ocular™ topical gel<br>* Topical gel for forehead dermal application<br>|
| Placebo Comparator: Placebo<br>Vehicle topical gel without active ingredient applied dermally to forehead twice daily, morning and before bedtime. | Drug: Placebo topical gel<br>* Topical gel for forehead dermal application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular pain from Glia OSD Symptoms Questionnaire | Change in ocular pain score | 1 hour | 
| Ocular discomfort | Change in ocular discomfort score | 1 hour | 
| Ocular discomfort | Change in ocular discomfort score | 2 weeks | 
| Corneal fluorescein staining | Change in fluorescein staining score | 10 weeks | 
| Conjunctival staining | Change in conjunctival staining score | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified SANDE | Change in SANDE score | 2 weeks | 
| Modified SANDE | Change in SANDE score | 6, 10 weeks | 
| Modified SANDE | Change in SANDE score | 10 weeks | 
| Glia OSD Symptoms Questionnaire | Change in total score | 1 hour | 
| Glia OSD Symptoms Questionnaire | Change in total score | 2 weeks | 
| Glia OSD Symptoms Questionnaire | Change in total score | 6 weeks | 
| Glia OSD Symptoms Questionnaire | Change in total score | 10 weeks | 
| Tear Film | Change in tear film score | 1 hour | 
| Tear Film | Change in tear film score | 2 weeks | 
| Tear Film | Change in tear film score | 6 weeks | 
| Tear Film | Change in tear film score | 10 weeks | 
| Conjunctival staining | Change in conjunctival staining score | 6 | 
| Lid margin | Change in lid margin abnormality score | 6 weeks | 
| Lid margin | Change in lid margin abnormality score | 10 weeks | 
| Ocular pain from Glia OSD Symptoms Questionnaire | Change in ocular pain score | 2 weeks | 
| Ocular pain from Glia OSD Symptoms Questionnaire | Change in ocular pain score | 10 weeks | 
| Ocular pain from Glia OSD Symptoms Questionnaire | Change in ocular pain score | 6 weeks | 
| Ocular discomfort | Change in ocular discomfort score | 6 weeks | 
| Ocular discomfort | Change in ocular discomfort score | 10 weeks | 
| Corneal fluorescein staining | Change in fluorescein staining score | 6 weeks | 
| NIH Chronic GvHD Eye Score | Change in eye score | 2 weeks | 
| NIH Chronic GvHD Eye Score | Change in eye score | 6 weeks | 
| NIH Chronic GvHD Eye Score | Change in eye score | 10 weeks |