Evidence map›Paper›PMID 39955261›Full record

Trial reportThe journal of prevention of Alzheimer's disease2025

Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease.

Erika N Cline, Daniel Antwi-Berko, Karen Sundell, Elizabeth Johnson, Maddelyn Hyland, Hao Zhang, Hugo Vanderstichele, June Kaplow, Robert A Dean, Erik Stoops and 7 more

Erratum issued 2 registry-linked trialsAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this 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.

NCT04931459 phase1completednot on this map

A Phase 1 Placebo-Controlled, Single- and Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous ACU193 in Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease

TypeinterventionalSponsorAcumen PharmaceuticalsRan2021 to 2023Enrolled65ConditionsAlzheimer DiseaseArmsACU193, Placebo
NCT06335173 phase2active not recruitingnot on this map

A Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Intravenous Sabirnetug in Early Alzheimer's Disease

TypeinterventionalSponsorAcumen PharmaceuticalsRan2024 to 2026Enrolled542ConditionsAlzheimer DiseaseArmssabirnetug, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Astrocytes provide a unique biomarker for Alzheimer's and other pathologies.The journal of prevention of Alzheimer's disease · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Erika N ClineAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA. Electronic address: ecline@acumenpharm.com.
Daniel Antwi-BerkoNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
Karen SundellAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Elizabeth JohnsonAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Maddelyn HylandAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Hao ZhangAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Hugo VandersticheleAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
June KaplowAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Robert A DeanAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Erik StoopsADx NeuroSciences, Technologiepark 6, Gent, Belgium.
Eugeen VanmechelenADx NeuroSciences, Technologiepark 6, Gent, Belgium.
Marleen J A Koel-SimmelinkNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
Charlotte E TeunissenNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
Gopalan SethuramanAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Todd FeasterAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Eric SiemersAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.
Jasna JerecicAcumen Pharmaceuticals, Inc, 1210-1220 Washington St., Suite 210, Newton, MA 02465, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveSabirnetug (ACU193) is a humanized monoclonal antibody selective for soluble amyloid beta oligomers (AβOs), synaptotoxins that are early and persistent triggers of Alzheimer's disease (AD). Sabirnetug pharmacodynamics were examined in the INTERCEPT-AD phase 1 study in mild cognitive impairment and mild dementia due to AD (NCT04931459) using biofluid biomarkers associated with Aβ and tau pathology, synaptic dysfunction, neuroinflammation, and neurodegeneration.

methodsINTERCEPT-AD was a randomized, first-in-human study of sabirnetug versus placebo administered as a single (SAD; 2, 10, 25, 60 mg/kg) or multiple (MAD; three doses of 10 or 60 mg/kg every 4 weeks [Q4W] or 25 mg/kg Q2W) ascending doses. Biomarkers were measured pre-/post-dose in CSF and EDTA-plasma. Correlations of biomarker changes versus dose, exposure duration, and target engagement were determined.

resultsIn MAD cohorts, CSF pTau181 decreased significantly (60 mg/kg Q4W, p = 0.049). VAMP2 decreased significantly at all doses (p ≤ 0.041); neurogranin decreased significantly at 60 mg/kg Q4W (p = 0.037). Aβ DISCUSSION: Following three sabirnetug doses, changes in CSF and plasma biomarkers were observed. The CSF biomarker response increased with increasing dose and exposure duration, consistent with previous reports that sabirnetug reaches the central compartment and engages its AβO target. The ongoing phase 2 ALTITUDE-AD study (NCT06335173) will test whether sabirnetug's pharmacodynamic effects can be substantiated with a larger sample size and longer treatment duration.

Indexed as

Alzheimer DiseaseAntibodies, Monoclonal, HumanizedCognitive DysfunctionAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersFemaleHumansMaleMiddle AgedPeptide Fragmentstau ProteinsAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkersPeptide Fragmentstau ProteinsACU193Alzheimer's diseaseBiomarkersCerebrospinal fluidSabirnetug

Identifiers

PMID39955261
PMCPMC12184040

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.