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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Keratoconjunctivitis Sicca, in Sjogren's Syndrome
• Intervention / Treatment: Drug: ASCs; Drug: Cryostor CS10

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • DK
    • Copenhagen, DK, Denmark, 2200
      • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Schirmer's I test	Change in tear production as evaluated with the Schirmer's I test	4 months after treatment
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
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

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Chair: Steffen Heegaard, MD, DMSc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Syndrome; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Sjogren's Syndrome; Keratoconjunctivitis
• Other Study ID Numbers: 2020-002804-38

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No