Evidence map›Paper›PMID 39621188›Full record

ArticleClinical drug investigation2025

Evaluation of NUN-004, a Novel Engineered Ephrin Antagonist, in Healthy Volunteers and Patients with Amyotrophic Lateral Sclerosis: A Phase I/Ib, Open-Label, Escalating Dose and Extended Access Study.

Michael Gerometta, Robert D Henderson, Richard Friend, Leanne T Cooper, Jing Zhao, Andrew W Boyd, Perry F Bartlett

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Clinical drug investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Michael GeromettaQueensland Brain Institute, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia. mike@biosensisconsulting.com.
Robert D HendersonUQ Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, QLD, 4029, Australia.
Richard FriendNucleus Network, Clive Berghofer Cancer Research Centre, Herston, QLD, 4006, Australia.
Leanne T CooperQueensland Brain Institute, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.
Jing ZhaoQueensland Brain Institute, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.
Andrew W BoydSchool of Medicine, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.
Perry F BartlettQueensland Brain Institute, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundErythropoietin-producing hepatocellular carcinoma A4 (EphA4) is implicated in the pathophysiology of amyotrophic lateral sclerosis. EphA4 fusion protein (EphA4-Fc) inhibits EphA4 function in vivo but is too short-lived for prolonged therapy. NUN-004 (mEphA4-Fc) is a modified EphA4-Fc engineered for an extended half-life.

objectiveThis first-in-human phase I/Ib study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and efficacy of NUN-004 in healthy volunteers and patients with amyotrophic lateral sclerosis.

methodsIn this open-label study, Part 1 enrolled 20 healthy volunteers in five single ascending dose cohorts (1, 3, 10, 20 and 30 mg/kg), followed by Part 2, which enrolled eight patients with amyotrophic lateral sclerosis in two multiple ascending dose cohorts (cycle 1: 15 and 30 mg/kg) who could continue into an extended access phase (cycles 2-6: 15 mg/kg) for a total of 6 months' treatment. All participants received intravenous NUN-004; multiple dosing was administered weekly in 28-day cycles. Primary endpoints included safety assessments, single-dose and multiple-dose pharmacokinetics, and anti-drug antibodies. Efficacy assessments were Amyotrophic Lateral Sclerosis Function Rating Score Revised (ALSFRS-R) and forced vital capacity.

resultsNUN-004 was well tolerated, with no serious adverse events or discontinuations. NUN-004 exposure generally increased with dose. Single-dose half-life was 111.7 (± 22.8) h in healthy volunteers (n = 20) and 74.4 (± 19.4) h in patients (n = 6). Steady state was observed in patients by day 8. Steady-state half-life (cycle 1 doses 2-4) was 83.7 (± 26.6) to 101.1 (± 46.0) h. No antibody response was observed. ALSFRS-R showed a slight improvement (+0.09 points/month) to cycle 4 and a slight decline (-0.35 points/month) over the whole study. Forced vital capacity trends were consistent with ALSFRS-R.

conclusionsThis study supports the safety, tolerability and extended half-life of NUN-004, and provides preliminary evidence for its ability to ameliorate disease progression in an amyotrophic lateral sclerosis cohort. CLINICAL

trial registrationRegistered on ANZCTR under identifier ACTRN12621000514808 (3 May, 2021).

Indexed as

Amyotrophic Lateral SclerosisReceptor, EphA4Recombinant Fusion ProteinsAdultAgedDose-Response Relationship, DrugFemaleHalf-LifeHealthy VolunteersHumansMaleMiddle AgedYoung AdultReceptor, EphA4Recombinant Fusion Proteins

Identifiers

PMID39621188

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.