Clinuvel Pharmaceuticals Limited has started its second stroke trial (CUV803) with the first patient receiving PRÉNUMBRA® Instant (afamelanotide), a new formulation. The Phase II study is evaluating the safety and efficacy of afamelanotide therapy in arterial ischaemic stroke (AIS) patients who are ineligible for the standard of care, consisting of either intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT). In total, up to twelve adult AIS patients will be enrolled, consisting of six patients with mild to moderate, and six with moderate to severe stroke, as reflected by the National Institutes of Health Stroke Scale (NIHSS).

Afamelanotide in arterial ischaemic stroke: AIS is caused by an arterial clot blocking blood supply to the brain. The resulting lack of oxygen and glucose causes immediate tissue death, with a larger area of the surrounding brain ­ known as the penumbra ­ at risk of further damage, due to fluid formation and inflammation. Patients suffer irreversible damage which, if not fatal, often leads to the permanent loss of mobility and/or speech.

AIS accounts for around 85% of the 15 million strokes incurred globally each year, with an estimated 70%-­80% ineligible for treatment with IVT or EVT. Melanocortins and afamelanotide are known to offer neuroprotection, providing potent antioxidative effects. Afamelanotide is suggested to increase blood flow and nutrients to the affected areas, as it is active on blood vessels and reduces fluid formation.

It thereby protects tissue and restores the blood brain barrier. The flexible PRÉNUMBRA® Instant formulation allows physicians to make faster dosing decisions, taking into account each individual patient's clinical need. The new afamelanotide formulation is expected to provide a faster clinical response.

In stroke, the speed of intervention is associated with an improved chance of recovery. In 2022, the first study in AIS, CUV801, five of six patients diagnosed with a mild to moderate stroke showed improved neurological function following afamelanotide, administered as a controlled-release implant. The treatment was well tolerated.

CUV803 study: Patients enrolled in the CUV803 study will receive an individually determined dose of PRÉNUMBRA® Instant for up to five consecutive days following a stroke. The study is conducted in acute neurological units in European expert centres. The study's objective is to evaluate the interventional drug as a possible option in AIS, evaluating its safety and efficacy.

The NIHSS will be used to assess overall disease severity. Cognitive functions will be measured using the Mini Mental State Examination (MMSE), and activities of daily living will be evaluated using the Activities of Daily Living questionnaire. Standardised neuroimaging tools (MRI/CT) will assess the volume and blood flow of the brain areas, affected by the stroke comparing imaging on Day of admission, Day 3, and Day 42.

Patients will be followed up for 42 days.