Subconjunctival Injection Of Liposomal Tacrolimus (Lipotac) For The Treatment Of Allergic Conjunctivitis: Pre-Clinical And Phase I Studies

To develop and evaluate the safety and efficacy of liposomal tacrolimus (LipoTac) in the treatment of vernal keratoconjunctivitis (VKC).

In-vitro drug release profiles, 2-year stability tests and efficacy tests using a VKC animal model were conducted. Subsequently, a phase 1 clinical trial was conducted on 4 patients with VKC.

Conjunctival tacrolimus levels were compared between 9 rabbits who underwent a single subconjunctival injection of 0.3ml of LipoTac and rabbits that received tacrolimus eye drops. 80 mice were randomly allocated into 4 groups (negative control, positive control, LipoTac, and blank liposome injections (LipoBlank)), examined weekly, and had immunohistochemical examinations at week 4. For the first-in-human trial, all 4 patients were followed up for 8 weeks with subjective and objective outcome measures including the Allergic Conjunctivitis Symptom (ACS) questionnaire, Ocular Symptom Score (OSS), VKC clinical grading, best corrected visual acuity (BCVA).

In vivo and in vitro testing showed a higher concentration of tacrolimus in the LipoTac group compared to the eye drop group at all time points. The expressions of pro-allergenic cytokines IL-4, IL-13, TGF-β1, and CD40L were all lower in the LipoTac group compared to the positive controls in mice eyes. 2-year stability tests showed that the pH 6.5 formulation had the least amount of tacrolimus degradation. First-in-man studies showed a significant improvement in OSS and ACS scores, with no change in BCVA. There were no serious adverse events recorded, with undetectable tacrolimus serum levels at all time points.

LipoTac is a safe and effective treatment option for sustained delivery of tacrolimus to treat VKC.