Evidence map›Paper›PMID 35180125›Full record

Trial reportJournal of Alzheimer's disease : JAD2022

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial.

Xue Hua, Kevin Church, William Walker, Philippe L'Hostis, Geoffrey Viardot, Philippe Danjou, Suzanne Hendrix, Hans J Moebius

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03298672 (A Randomized, Placebo-Controlled, Double-Blinded, First-in-Human Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses), which is not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 7% of its field
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.

NCT03298672 phase1completednot on this map

A Randomized, Placebo-Controlled, Double-Blinded, First-in-Human Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part A) and Multiple Ascending Doses (Part B) of NDX-1017 in Healthy Young and Elderly Subjects

TypeinterventionalSponsorLeonaBioRan2017 to 2019Enrolled88ConditionsAlzheimer DiseaseArmsNDX-1017, Placebo
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
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  6. Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics.PCN reports : psychiatry and clinical neurosciences · 2024
    Article
  7. Review
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  11. Article
  12. Review
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  14. Fosgonimeton in mild-to-moderate Alzheimer's disease.Journal of Alzheimer's disease reports
    Article
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

8 authors at 2 institutions in 1 country.

Xue HuaAthira Pharma, Inc., Bothell, WA, USA.
Kevin ChurchAthira Pharma, Inc., Bothell, WA, USA.
William WalkerAthira Pharma, Inc., Bothell, WA, USA.
Philippe L'HostisCore Lab, Drug Evaluation and Pharmacology Research, Biotrial, Rennes, France.
Geoffrey ViardotCore Lab, Drug Evaluation and Pharmacology Research, Biotrial, Rennes, France.
Philippe DanjouPhase 1 Unit, Drug Evaluation and Pharmacology Research, Biotrial, Newark, NJ, USA.
Suzanne HendrixPentara Corporation, Millcreek, UT, USA.
Hans J MoebiusAthira Pharma, Inc., Bothell, WA, USA.
Athira Pharma (United States) · USTetraLogic Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFosgonimeton (ATH-1017) is being developed as a first-in-class regenerative therapy for people with Alzheimer's disease (AD) and dementia; potentially improving dementia symptoms and altering disease progression by reversing synaptic disconnection and neuronal loss.

objectiveThis randomized, double-blind, placebo-controlled phase I trial (NCT03298672) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of fosgonimeton.

methodsFosgonimeton was administered once daily via subcutaneous injection to 88 subjects. The single ascending dose study enrolled healthy young male subjects (n = 48; age, 33.4±6.3 years; dose, 2, 6, 20, 40, 60, or 90 mg); the multiple ascending dose study enrolled healthy elderly subjects (n = 29; age, 63.8±4.0 years; dose, 20, 40, 60, or 80 mg; 9-day duration); and the fixed-dose study enrolled AD subjects (n = 11; age, 69.2±7.1 years; dose, 40 mg; 9-day duration). Quantitative electroencephalogram (qEEG) and event-related potential (ERP) P300 measured neurophysiological signals following fosgonimeton treatment, supporting brain penetration and target engagement.

resultsFosgonimeton and placebo were shown to be safe and well-tolerated across all doses. Pharmacokinetic results for fosgonimeton were dose-proportional, with no sex effect or accumulation over 9 days. The main effect of fosgonimeton on qEEG was acute and sustained gamma power induction. In AD subjects, there was a significant effect toward ERP P300 latency normalization compared with placebo (p = 0.027; n = 7 at 40 mg fosgonimeton versus n = 4 placebo).

conclusionThese results support the continued development of fosgonimeton as a novel therapeutic for people with AD and dementia. The fast-onset normalization of ERP P300 latency in AD subjects suggests enhancement of synaptic function and potential procognitive effects.

Indexed as

Alzheimer DiseaseAgedArea Under CurveDose-Response Relationship, DrugDouble-Blind MethodHealthy VolunteersHepatocyte Growth FactorHumansMaleHepatocyte Growth FactorHGF protein, humanAlzheimer’s diseaseATH-1001ATH-1017dementiaelectroencephalographyevent-related potentialsfosgonimetonhepatocyte growth factorneurotrophic factorP300 component

Identifiers

PMID35180125
PMCPMC9108585
OpenAlexW4213146203

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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Registered trials

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.