A feasibility and safety study of afamelanotide in acute stroke patients - an open label, proof of concept, phase iia clinical trial.

Stanislaus V, Kam A, Murphy L, Wolgen P, Walker G, Bilbao P, Cloud GC

BMC neurology26 Jul 2023Cited by 3 (Europe PMC)

PMID37496004PMCIDPMC10373257DOI10.1186/s12883-023-03338-9PepBankPUB-37496004

Summary

BackgroundNeuroprotective 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.MethodsAIS patients within 24 h 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.ResultsSix 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.ConclusionsAfamelanotide 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.ClinicaltrialsGov identifierNCT04962503, First posted 15/07/2021.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanNon-randomized trialSafety outcome
In 6 patients with acute ischemic stroke given afamelanotide implants, one patient who received 2 doses died of a recurrent stroke on D9, assessed as unrelated to the study drug.
In plain wordsIn 6 stroke patients given afamelanotide, one died of a new stroke on day 9. The study judged this unrelated to the drug.
Peptide
Melanotan I (afamelanotide)
Outcome
Not applicableFatal recurrent stroke
Study
n = 6
Outcome group
Mortality · Nervous system and cognition
Studied dose
16 mg implant · subcutaneous · 2 to 4 implants, D0 to D8As given in this study (human).
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
AIS patients within 24 h of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled.
Summary · context
Six patients (5 women, median age 81, median NIHSS 6) were recruited.
Show in the study text Report a problemFND-3749600401
02HumanNon-randomized trialSafety outcome
In 6 patients with acute ischemic stroke given afamelanotide implants, no other local or major systemic treatment emergent adverse events were recorded.
In plain wordsIn 6 stroke patients given afamelanotide, no other local or major body-wide side effects were recorded.
Peptide
Melanotan I (afamelanotide)
Outcome
No significant changeOther treatment emergent adverse events
Study
n = 6
Outcome group
Adverse events · Nervous system and cognition
Studied dose
16 mg implant · subcutaneous · 2 to 4 implants, D0 to D8As given in this study (human).
Source sentences
Summary
There were no other local or major systemic TEAEs recorded.
2 context sentences(design, population, supporting numbers)
Summary · context
AIS patients within 24 h of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled.
Summary · context
Six patients (5 women, median age 81, median NIHSS 6) were recruited.
Show in the study text Report a problemFND-3749600402
03HumanNon-randomized trialEfficacy outcome
In surviving patients with acute ischemic stroke given afamelanotide, the median NIHSS improved from 6 to 2 on D7, without a control group.
In plain wordsIn stroke patients who survived after afamelanotide, the median stroke severity score improved from 6 to 2 by day 7.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseMedian NIHSS at D7
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
16 mg implant · subcutaneous · 2 to 4 implants, D0 to D8As given in this study (human).
Measurements
median NIHSS
6 points
baseline
median NIHSS
2 points
D7
Source sentences
Summary
In all surviving patients, the median NIHSS improved from 6 to 2 on D7.
2 context sentences(design, population, supporting numbers)
Summary · context
AIS patients within 24 h of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled.
Summary · context
Six patients (5 women, median age 81, median NIHSS 6) were recruited.
Show in the study text Report a problemFND-3749600403
04HumanNon-randomized trialEfficacy outcome
In patients with acute ischemic stroke given afamelanotide, median Tmax volume of 23 mL on D0 fell to a FLAIR volume of 10 mL on D3 and 4 mL on D9.
In plain wordsIn stroke patients given afamelanotide, median affected brain volume fell from 23 mL to 10 mL on day 3, then 4 mL.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseTmax and FLAIR lesion volume on MRI
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
16 mg implant · subcutaneous · 2 to 4 implants, D0 to D8As given in this study (human).
Measurements
median Tmax volume
23 mL
D0
median FLAIR volume
10 mL
D3
median FLAIR volume
4 mL
D9
Source sentences
Summary
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.
2 context sentences(design, population, supporting numbers)
Summary · context
AIS patients within 24 h of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled.
Summary · context
Six patients (5 women, median age 81, median NIHSS 6) were recruited.
Show in the study text Report a problemFND-3749600404

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT04962503

A Proof of Concept Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS)

Clinuvel Pharmaceuticals Limitedn = 63 Jun 2021 to 4 Feb 2022

Arterial Ischemic Stroke

Trial page ClinicalTrials.govUpdated 11 Apr 2023

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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