Study on Safety and Performance of an Artificial Tear in Dry Eye Treatment in Subjects With Ocular Surface Inflammation

Dry Eye Disease Clinical Trial

Official title:

Pilot Study on Safety and Performance of an Artificial Tear Containing Arabinogalactan, Trehalose and Hyaluronic Acid in the Treatment of Dry Eye in Subjects With Inflammation of the Ocular Surface

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04633863
• Other study ID #: MDI - 101
• Status: Completed
• Phase: N/A
• Start date: October 12, 2020
• Est. completion date: November 30, 2021

Study information

• Verified date: December 2021
• Source: MD Italy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is post-market study to evaluate the safety and efficacy of MDI - 101 a novel tear substitute for the treatment of dry eye (DE) in subjects with evidence of inflammation of the ocular surface. In particular, this study intends to evaluate, in a cohort of 25 patients, the anti-inflammatory properties of the product under study over a period of 10 weeks

Description:

DE is a common eye condition that affects 1 to 2 out of 10 persons in the world. Regardless of the underlying ethology, DE is associated with increased inflammation of conjunctiva, cornea and adnexa. As consequence of the recognized role of the inflammation in the etiopathogenesis of DE, direct and indirect anti-inflammatory treatments are currently the cornerstone for the management of DE, leading to the inhibition of the expression of inflammatory mediators on the ocular surface, therefore restoring the secretion of a healthy tear film and consequently reducing signs and symptoms of DE. MDI - 101, the product under study containing arabinogalactan (AG), trehalose and hyaluronic acid (HA) ,is a medical device with European Conformity (CE) mark that, thanks to the muco-adhesive proprieties of AG enriches the natural mucous of the tear film providing enhanced lubrication and protection and anti-inflammatory properties, in combination with trehalose and HA. The aim of this study is to demonstrate that the reduced ocular discomfort and the improvement of the integrity of the ocular surface are due to the interruption of the "vicious cycle of inflammation". This open-label study involves a cohort of 24 patients with clinical and instrumental signs of inflammation of the ocular surface and includes end-points of efficacy, safety and evaluation of inflammation markers. The study includes 6 visits over 10 weeks, 8 of which of active treatment. This study is conducted during the Covid-19 pandemic and for this reason, clinical assessments of all the 24 patients are carried out remotely, from patients' home, with the adoption of digital solutions that determine: reduction of 66% of physical contacts between investigator and patient, a total of 90% of efficacy and safety data collected remotely and a reduction of 100% of physical contacts between investigator and clinical monitor, keeping the study entirely within the Good Clinical Practice framework.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 30, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Subjects who gave their written consent for participation in the study and for personal data processing and willing to comply with all study procedures.

2. Males or females 30-75 years old.

3. Subjects who are familiar with the needs of the study in the use of mobile devices and internet.

4. Subjects who successfully completed the electronic registration for the clinical trial using their own study electronic Patient Reported Outcome (ePRO) profile and completed the OSDI questionnaire.

5. Subjects who had been diagnosed as having dry eye symptoms for at least 3 months, fulfilling all the following four criteria: i. OSDI score of >18 evaluated by the questionnaire of Ocular Surface Disease Index (OSDI); ii. Non-invasive breakup time (NIBUT) =10 seconds at least in one eye; iii. Levels of MMP-9 in tears = 40 ng/ml as assessed by the Inflammatory assay at least in one eye; iv. Cornea surface scores =1 and <4, based on Efron grading system. -

Exclusion Criteria:

1. Contact lens wearers.

2. Subjects who did use any artificial tear for at least 7 days before baseline.

3. Severe corneal damage (cornea surface scores =4, based on Efron grading system) or cornea surface normal (scores <1 based on Efron grading system)

4. Corneal abrasions or other corneal abnormalities, blepharitis, meibomitis, lid abnormalities.

5. Conjunctivitis of infective or allergic origins, ongoing or resolved less than 4 weeks before baseline visit.

6. Subjects participating in another clinical study, on-going or completed less than 4 weeks before.

7. Subject using, or will use during the study, other artificial tear or other ophthalmic products including, but not limited, to: corticosteroids, antibiotics, vasoconstrictor agents.

Related Conditions & MeSH terms

• Dry Eye Disease
• Dry Eye Syndromes
• Eye Diseases
• Inflammation
• Keratoconjunctivitis Sicca

Intervention

Device:
• Artificial tear MDI - 101
Medical device CE marked - artificial tears containing arabinogalactan, trehalose and hyaluronic acid - 10 weeks treatment

Locations

Country	Name	City	State
Italy	Ophthalmology unit	Lucca

Sponsors (3)

Lead Sponsor	Collaborator
MD Italy	Hippocrates Research, Nubilaria Srl

Country where clinical trial is conducted

Italy, 

References & Publications (18)

Battelli MG, Bolognesi A, Polito L. Pathophysiology of circulating xanthine oxidoreductase: new emerging roles for a multi-tasking enzyme. Biochim Biophys Acta. 2014 Sep;1842(9):1502-17. doi: 10.1016/j.bbadis.2014.05.022. Epub 2014 May 29. Review. — View Citation

Baudouin C. [A new approach for better comprehension of diseases of the ocular surface]. J Fr Ophtalmol. 2007 Mar;30(3):239-46. French. — View Citation

Bron AJ, de Paiva CS, Chauhan SK, Bonini S, Gabison EE, Jain S, Knop E, Markoulli M, Ogawa Y, Perez V, Uchino Y, Yokoi N, Zoukhri D, Sullivan DA. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul;15(3):438-510. doi: 10.1016/j.jtos.2017.05.011. Epub — View Citation

Burgalassi S, Nicosia N, Monti D, Falcone G, Boldrini E, Chetoni P. Larch arabinogalactan for dry eye protection and treatment of corneal lesions: investigations in rabbits. J Ocul Pharmacol Ther. 2007 Dec;23(6):541-50. — View Citation

Cejka C, Kubinova S, Cejkova J. Trehalose in ophthalmology. Histol Histopathol. 2019 Jun;34(6):611-618. doi: 10.14670/HH-18-082. Epub 2019 Jan 9. Review. — View Citation

Choy CK, Cho P, Boost MV. Cytotoxicity of rigid gas-permeable lens care solutions. Clin Exp Optom. 2013 Sep;96(5):467-71. doi: 10.1111/cxo.12039. Epub 2013 May 3. — View Citation

Efron N, Morgan PB, Jagpal R. Validation of computer morphs for grading contact lens complications. Ophthalmic Physiol Opt. 2002 Jul;22(4):341-9. — View Citation

Hessen M, Akpek EK. Dry eye: an inflammatory ocular disease. J Ophthalmic Vis Res. 2014 Apr;9(2):240-50. Review. — View Citation

Holden BA, Reddy MK, Sankaridurg PR, Buddi R, Sharma S, Willcox MD, Sweeney DF, Rao GN. Contact lens-induced peripheral ulcers with extended wear of disposable hydrogel lenses: histopathologic observations on the nature and type of corneal infiltrate. Cor — View Citation

Jain NK, Roy I. Effect of trehalose on protein structure. Protein Sci. 2009 Jan;18(1):24-36. doi: 10.1002/pro.3. Review. — View Citation

Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. Altern Med Rev. 1999 Apr;4(2):96-103. Review. — View Citation

Li W, Sun X, Wang Z, Zhang Y. A survey of contact lens-related complications in a tertiary hospital in China. Cont Lens Anterior Eye. 2018 Apr;41(2):201-204. doi: 10.1016/j.clae.2017.10.007. Epub 2017 Oct 21. — View Citation

Pahuja P, Arora S, Pawar P. Ocular drug delivery system: a reference to natural polymers. Expert Opin Drug Deliv. 2012 Jul;9(7):837-61. doi: 10.1517/17425247.2012.690733. Epub 2012 Jun 16. Review. — View Citation

Shi YH, Zhou LT, Zhang CX, Li YZ, Zhang JZ, Zhou HM, Li YG, Liu T, Zhang LL, Sun LN, Chen Z. Effects of carbomer eye drops in combination with orthokeratology lens in treating adolescent myopia. J Biol Regul Homeost Agents. 2016 Oct-Dec;30(4):1029-1033. — View Citation

Silvani L, Bedei A, De Grazia G, Remiddi S. Arabinogalactan and hyaluronic acid in ophthalmic solution: Experimental effect on xanthine oxidoreductase complex as key player in ocular inflammation (in vitro study). Exp Eye Res. 2020 Jul;196:108058. doi: 10 — View Citation

Stuart JC, Linn JG. Dilute sodium hyaluronate (Healon) in the treatment of ocular surface disorders. Ann Ophthalmol. 1985 Mar;17(3):190-2. — View Citation

Sullivan DA, Rocha EM, Aragona P, Clayton JA, Ding J, Golebiowski B, Hampel U, McDermott AM, Schaumberg DA, Srinivasan S, Versura P, Willcox MDP. TFOS DEWS II Sex, Gender, and Hormones Report. Ocul Surf. 2017 Jul;15(3):284-333. doi: 10.1016/j.jtos.2017.04 — View Citation

Yokoi N, Komuro A. Non-invasive methods of assessing the tear film. Exp Eye Res. 2004 Mar;78(3):399-407. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy - Ocular Surface Disease Index (OSDI)	Change of OSDI score versus baseline at any study time-point. The main goal of the study is to gather information about the efficacy, assessed by OSDI (Ocular Surface Disease Index) questionnaire, of artificial tear containing AG, trehalose and HA (MDI - 101) used in the treatment of symptoms of DE of various aetiology, with evidence of inflammation of the ocular surface. The OSDI score ranges from 0 (better outcome) to 100 (worst outcome)	1 week - 2 weeks - 4 weeks - 6 weeks - 8 weeks
Secondary	Additional efficacy parameters: Matrix Metalloproteinase 9 (MMP-9)	Change of tear matrix metalloproteinase(MMP)-9 at T0 vs final assessment. The result of the MMP test could be NEGATIVE if the level of MMP-9 is < 40 ng/ml (better outcome) or POSITIVE if the level of MMP-9 is = 40 ng/ml (worst outcome)	8 weeks
Secondary	Additional Efficacy parameters: EFRON SCALE	Change of Efron Grading Scales at T0 vs final assessment. The Efron grading scale range from 0 (cornea surface normale) to 4 (severe corneal damage)	8 weeks
Secondary	Additional Efficacy parameters: Corneal and Conjunctival Staining	Change of Corneal and Conjunctival Staining at T0 vs final assessment. The Staining scale ranges from 0 (better outcome) to 3 (worst outcome)	8 weeks
Secondary	Additional Efficacy parameters: NIBUT	Change of NIBUT at T0 vs final assessment. The result of the Non-Invasive Break-Up Time (NIBUT) test could be >10 seconds (better outcome) or =10 seconds (worst outcome)	8 weeks
Secondary	Additional Efficacy parameters: Osmolarity	Change of Osmolarity at T0 vs final assessment. The higher the tear film osmolarity, the greater the severity of the ocular surface damage.	8 weeks
Secondary	Additional Efficacy parameters: Ocular Protection Index	Change of Ocular Protection Index (OPI) at T0 vs final assessment The principle of the test is that when BUT is shorter than the blink interval, the eyes are exposed to the risk of focal ocular surface damage.	8 weeks
Secondary	Additional Efficacy parameters: meniscometry	Change of meniscometry at T0 vs final assessment. The lowest tear meniscus radius, the higher the severity of the ocular surface health	8 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety Adverse Event (AE) experienced with the artificial tear assessed by the patient, before the ocular examination or reported by the patient at any time during the study.	8 weeks
Secondary	Incidence of change in the unaided and corrected visual acuity	Unaided and corrected visual acuity Snellen test will be performed to evaluate change in the unaided and corrected visual acuity at T0 vs final assessment.	8 weeks
Secondary	Incidence of change in the Intraocular pressure	Change of Intraocular pressure at T0 vs final assessment.	8 weeks
Secondary	Evaluation of the Tolerability Signs and symptoms of discomfort	Treatment adherence assessed by the patient at any study time-point (number of instillations in the past 24 hours).	8 weeks
Secondary	Treatment adherence (24 hours)	Treatment adherence assessed by the patient at any study time-point (number of instillations in the past 24 hours)	8 weeks
Secondary	Treatment adherence (total days)	Treatment adherence assessed by the patient at any study time-point (number of days of product usage).	8 weeks