Retrospective Chart Review of Patients With Acanthamoeba Keratitis Who Have Received 0.8 mg/ml Polihexanide as Part of a Compassionate Use Program: A Non-interventional Study With Secondary Use of Data

Acanthamoeba keratitis (AK) is an ultra-rare potentially devastating ocular infection that occurs primarily in contact lens wearers. The estimated incidence in Europe varies between 1 and 3 cases/million people per year. AK is caused by a ubiquitous free-living protozoan that is present in air, soil, dust, fresh water, seawater, and bottled water. The amoebic organism exists both as dormant cysts and active trophozoites. The cysts are highly resilient and can withstand a wide variety of physical conditions and drugs which makes medical treatment of AK both difficult and protracted. If left untreated, the cure rate is low with most patients needing keratoplasty and some of them requiring enucleation. There is currently no approved pharmacological treatment for AK. Available treatment options are represented by off-label antiseptic products which are either imported or compounded, the most used being biguanides (polihexanide-PHMB- or chlorhexidine), given alone or in combination with a diamidine (propamidine or hexamidine). The actual reported medical cure rate with no surgery is approximately 60%; in addition almost 50% of patients have a poor outcome, defined as a poor visual acuity and/or necessity of ocular surgery. Polihexanide 0.8 mg/ml, an eye drops solution developed and manufactured by SIFI SpA (Italy), has the potential to become the first treatment approved for the treatment of AK. Its efficacy and safety were demonstrated in the pivotal clinical study 043/SI (EUDRACT no. 2016-001823-30; ClinicalTrials.gov: NCT03274895), in which the mean (95% IC) cure rate with no surgery was 84.8% (73.9-92.5) with a median (95% IC) time-to-cure of 146 (94-217) days. In addition, no major safety issues were observed during the trial. A positive opinion from the Committee for Medicinal Products for Human Use at EMA is expected in Q2/2024. Polihexanide 0.8 mg/ml has been made available in Italy by SIFI S.p.A. through a compassionate use program (CUP) since November 2022 (Compassionate use program, version 1.1-ITA-Aug 11, 2022). As of December 2023, the treatment with 0.8 mg/ml polihexanide was approved for 71 patients with AK. SIFI prepared this protocol to conduct a retrospective medical chart review of patients which already completed the treatment with 0.8 mg/ml polihexanide as part of the CUP. The expected number of evaluable patients is 40. According to the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) this will be a Non-Interventional Study (as defined in the Directive 2001/20/EC) with secondary use of data. The protocol was prepared following the good practices report of the ISPE/ISPOR task force.

The expected contribution from this study will be to expand patient's exposure to polihexanide 0.8 mg/ml and provide further information on its effectiveness and safety when used in the clinical practice compared with the findings observed in the pivotal clinical trial.