Intervention: Piclidenoson
Trial phase: Phase 3
SMILES: CNC(=O)[C@H]1O[C@@H](n2cnc3c(NCc4ccc(I)cc4)ncnc32)[C@H](O)[C@@H]1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 81
Group description: CF101: orally q12h
Eligibility criteria:
Inclusion Criteria:

Male or female, 18 years of age and over;

Have a diagnosis of moderate-to-severe Aqueous-Deficient Dry Eye (including Sjögren's Syndrome dry eye), as defined by:

Positive corneal fluorescein staining (FS), defined as a corneal punctate fluorescein staining score of ≥4 in either eye by the National Eye Institute evaluation scale summed over 5 areas each with a 0-3 scoring scale; AND
FS score of ≥2 in at least one corneal region; AND
Schirmer Test (ST) score (without anesthesia) ≥1 mm and < 7 mm/5 min in either eye; AND
OSDI score of ≥20;
Central corneal FS score of ≥2 in at least 1 eye;
Willing to use no topical ocular treatments, other than REFRESH® unpreserved artificial tears up to a maximum of 4 times daily, for the duration of the trial (including the 2-week run-in period, the 24-week treatment period and the 2-week follow-up period);
Willing to forego periocular cosmetic application for the duration of the trial;
Females of child-bearing potential must have a negative urine pregnancy test at screening and throughout the study, to be eligible for, and continue participation in, the study;
Females of child-bearing potential must be willing to use 2 methods of contraception deemed adequate by the Investigator (for example oral contraceptive pills plus a barrier method) to be eligible for, and continue participation in, the study;
Ability to complete the study in compliance with the protocol; and
Ability to understand and provide written informed consent.

Exclusion Criteria:

Sjögren's Syndrome with significant systemic non-exocrine gland involvement which, in the investigator"s opinion, would interfere with the conduct of the trial;
Stevens-Johnson Syndrome;
Use of methotrexate or systemic cyclosporine within the 3 months prior to the Screening Visit;
of any other disease-modifying anti-rheumatic therapy within 2 months prior to the Screening Visit;
Use of any anti-rheumatic biological agent within 2 months, or 5 half-lives, whichever is longer, prior to the Screening Visit;
Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
Use of topical steroids within 4 weeks prior to the Screening Visit and for the duration of the study;
Receipt of topical cyclosporine eye drops within 3 months prior to the Screening Visit and for the duration of the trial;
Use of oral statin or preparation containing omega-3 fatty acid unless dose has been stable for at least 3 months and will remain so during the course of the trial;
Presence of chronic ocular disease other than Aqueous-Deficient Dry Eye requiring topical treatment;
Presence of post-burn ocular injury;
Ocular herpes simplex virus infection;
Concomitant use of contact lenses or use within 3 months prior to the Screening Visit;
Persistent intraocular inflammation or infection;
Active anterior blepharitis of greater than mild degree, defined as minimal crust at the base of the eyelashes and no signs of inflammation;
Meibomian gland dysfunction (MGD) of greater than mild degree, defined as mild plugging of the Meibomian glands without lid margin inflammation;
Surgical occlusion of the lacrimal puncta, including the insertion of punctual plugs, within 3 months of the Screening Visit.