Silk-Derived Protein-4 (SDP-4) versus a novel sodium acetate vehicle in the treatment of patients with moderate to severe dry eye disease: a randomized, dual cohort, controlled trial

Abstract

Abstract Background: Dry eye disease (DED) affects over 400 million people globally, with 120 million Americans spending $3 billion per year on eye drops to treat their symptoms that significantly reduce their quality of life from reduced vision and chronic suffering. There is a significant unmet need for products that provide both immediate relief and long-term symptom reduction. The amphiphilic, mucin-like, chemistry of silk-derived protein-4 (SDP-4) enhances coating on the ocular surface to improve tear film stability and comfort. Additionally, previous studies support that both SDP-4 and sodium acetate inhibit inflammation, which is a known and significant driver of DED symptomatology. Methods: Preservative free eye drops were formulated with sodium acetate buffer as a vehicle, in which SDP-4 was added at 0.1%, 1%, and 3% wt./wt. concentrations. The product was evaluated in an exploratory Phase 2 clinical study that compared the treatment effect of SDP-4 vs vehicle in patients with moderate-to-severe or only moderate baseline symptomatology (N = 456, n1=305, n2=151). Patients were dosed twice daily (BID) for a period of up to 84 days. Results: The best performing dosing arm, 1% SDP-4, increased tear film stability and reduced DED symptoms by the first week of treatment with continued reduction in symptoms through the 84-day study period. The treatment significantly increased the DED sign of Tear Breakup Time (TBUT) vs the vehicle control (P<0.05) at days 28 and 56. TBUT is an accepted measure of tear film stability. Furthermore, patient symptomatology from baseline was reduced by 46% based on subjectively reported Symptom Assessment iN Dry Eye (SANDE) visual analog scale (VAS) scores at day 84. Most importantly, patients with severer baseline DED experienced a significantly greater reduction in symptomatology than patients with moderate baseline DED (P<0.01). For all patients, SDP-4 and the vehicle was well tolerated throughout the study with a low 2.6% discontinuation rate. Conclusions: The favorable combination of safety, comfort, and symptom reduction positions SDP-4 sodium acetate formulations as an innovative approach for treating DED by simultaneously providing immediate comfort at use, and addressing the symptomatology in the difficult to treat severe DED patient population. Trial registration Name of registry: www.ClinicalTrials.gov Trial registration numbers: NCT03889886 (first cohort) and NCT04535947 (second cohort) Date of registration: March 26, 2019 URL of trial registry record: clinicaltrials.gov/ct2/show/NCT03889886 (first cohort) and clinicaltrials.gov/ct2/show/NCT04535947 (second cohort)