A Feasibility and Safety Study of Afamelanotide in Acute Stroke Patients – An Open Label, Proof of Concept, Phase Iia Clinical Trial
Afamelanotide shows promise as a safe neuroprotective agent in acute ischemic stroke, but larger trials are needed to confirm efficacy.
Where it sits
this study against the rest of the afamelanotide corpusSummary and findings
This study assessed the feasibility and safety of afamelanotide in acute ischemic stroke patients ineligible for revascularisation. Six patients received 16 mg subcutaneous implants, with neurological and imaging assessments up to 42 days. Afamelanotide was well tolerated, with improvements in NIHSS scores and MRI findings.
Abstract
BACKGROUND Neuroprotective agents have the potential to improve the outcomes of revascularisation therapies in acute ischemic stroke patients (AIS) and in those unable to receive revascularisation. Afamelanotide, a synthetic α-melanocyte stimulating hormone analogue, is a potential novel neuroprotective agent. We set out to assess the feasibility and safety of afamelanotide for the first time in AIS patients. METHODS AIS patients within 24 hours of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled. Afamelanotide 16 mg implants were administered subcutaneously on Day 0 (D0, day of recruitment), D1 and repeated on D7 and D8, if not well recovered. Treatment emergent adverse events (TEAEs) and neurological assessments were recorded regularly up to D42. Magnetic resonance imaging (MRI) with FLAIR sequences were also performed on D3 and D9. RESULTS Six patients (5 women, median age 81, median NIHSS 6) were recruited. Two patients received 4 doses and four patients received 2. One patient (who received 2 doses), suffered a fatal recurrent stroke on D9 due to a known complete acute internal carotid artery occlusion, assessed as unrelated to the study drug. There were no other local or major systemic TEAEs recorded. In all surviving patients, the median NIHSS improved from 6 to 2 on D7. The median Tmax volume on D0 was 23 mL which was reduced to a FLAIR volume of 10 mL on D3 and 4 mL on D9. CONCLUSIONS Afamelanotide was well tolerated and safe in our small sample of AIS patients. It also appears to be associated with good recovery and radiological improvement of salvageable tissue which needs to be tested in randomized studies. ClinicalTrials.gov Identifier: NCT04962503
Background
Acute ischemic stroke (AIS) patients often benefit from revascularisation therapies, but some are ineligible for such treatments. Neuroprotective agents like afamelanotide, a synthetic α-melanocyte stimulating hormone analogue, may offer alternative benefits. This study explores the feasibility and safety of afamelanotide in AIS patients, a novel approach in this context.
Methods
This was an open-label, phase IIa clinical trial involving six AIS patients within 24 hours of onset with perfusion abnormalities. Patients received 16 mg afamelanotide implants subcutaneously on Day 0, Day 1, and repeated on Day 7 and Day 8 if not well recovered. The primary outcomes were treatment emergent adverse events and neurological assessments up to Day 42, with MRI imaging on Days 3 and 9.
Results
Among the six patients, the median NIHSS score improved from 6 at baseline to 2 by Day 7. MRI results showed a reduction in median Tmax volume from 23 mL on Day 0 to 4 mL on Day 9. One patient experienced a fatal recurrent stroke on Day 9, deemed unrelated to the study drug. No other major systemic adverse events were reported.
Interpretation
The study suggests that afamelanotide is safe and potentially beneficial in improving neurological outcomes in AIS patients who cannot undergo revascularisation. However, the small sample size and open-label design limit the generalizability of the findings. Larger randomized controlled trials are needed to confirm these preliminary results and assess the clinical significance of the observed improvements.
Key findings
- Six patients enrolled, median age 81, median NIHSS 6.
- Afamelanotide 16 mg implants administered on D0, D1, D7, and D8.
- Median NIHSS improved from 6 to 2 by D7.
- Median Tmax volume reduced from 23 mL on D0 to 4 mL on D9.
- One fatal recurrent stroke on D9, unrelated to study drug.
Limitations
- small n=6
- open-label design
- single-site study
- preliminary findings
- not randomized