Mesenchymal Stem Cell Therapy of Dry Eye Disease in Patients With Sjögren's Syndrome

Study Overview
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Brief Summary
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AMASS is a double-blinded randomized clinical trial with the purpose of investigating whether injection of allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) results in increased ocular comfort compared to placebo.

Detailed Description
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AMASS is a double-blinded randomized clinical trial which will be performed at the Department of Ophthalmology, University Hospital of Copenhagen, Denmark. 40 patients with severe aqueous deficient dry eye disease (ADDE) due to Sjögren's Syndrome (SS) will be recruited from the Dept. of Ophthalmology, Rigshospitalet, and allocated in ratio 1:1 to either injection of allogeneic adipose-derived mesenchymal stem cells (ASCs) or placebo (vehicle, Crystore CS10) into the lacrimal gland (LG) in one eye. We hypothesize that injection of allogeneic ASCs into the LG increases tear production and reduce inflammation resulting in increased ocular comfort compared to placebo.

Official Title
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A Randomized Clinical Trial Evaluating Allogeneic Adipose-derived MesenchymAl Stem Cells as a Treatment of Dry Eye Disease in Patients With Sjögren's Syndrome

Conditions
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Keratoconjunctivitis Sicca, in Sjogren's Syndrome

Intervention / Treatment
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* Drug: ASCs
* Drug: Cryostor CS10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Sjögren's syndrome according to the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome OSDI-score ≥ 33 Schirmer's test 1-5 mm/5 minutes NIKBUT < 10 sec Exclusion Criteria: LG volume on MRI < 0,2 cm3 in the study eye Previous treatment with ASCs or other stem cell products in the LG(s) Reduced immune response (e.g. HIV positive) Pregnancy or planned pregnancy within the next 2 years Breastfeeding Topical treatment with eye drops other than to treat dry eye disease (DED) Any other disease/condition judged by the investigator to be grounds for exclusion, such as infection in or around the eye

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 |
| --- | --- |
| Experimental: Adipose tissue-derived mesenchymal stem cells (ASCs)<br>One transconjunctival injection of allogeneic ASCs into the LG in one eye. | Drug: ASCs<br>* ASCs expanded from healthy donors. The ASC product contains 22 million ASCs/ml.<br>* Other names: Allogeneic adipose-derived mesenchymal stem cells;|
| Placebo Comparator: Placebo (vehicle, Cryostor CS10)<br>One transconjunctival injection of Cryostor CS10 into the LG in one eye. | Drug: Cryostor CS10<br>* CryoStor® CS10 freeze medium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index (OSDI) | The OSDI is a valid and reliable instrument for measuring dry eye disease severity | 4 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-invasive keratography tear break-up time (NIKBUT) | As measured with the Keratograph 5M (Oculus™) | 4 months after treatment | 
| Tear meniscus height (TMH) | As measured with the Keratograph 5M (Oculus™) | 4 months after treatment | 
| Schirmer's I test | Change in tear production as evaluated with the Schirmer's I test | 4 months after treatment | 
| Tear osmolarity | Change in tear osmolarity measured with TearLab™ | 4 months after treatment | 
| Oxford scale | Change in staining of the ocular surface (grade 0-5 with 0 being absent corneal staining and 5 being severe corneal staining) | 4 months after treatment | 
| HLA anti-bodies | Development of anti-human leucocyte antigen (HLA) anti-bodies evaluated with Luminex HLA anti-body screening Development of anti-HLA anti-bodies evaluated with Luminex HLA anti-body screening Development of donor-specific HLA-antibodies | 12 months after treatment |