Evidence map›Paper›PMID 38970127›Full record

Trial reportAlzheimer's research & therapy2024

A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease.

Douglas Galasko, Martin R Farlow, Brendan P Lucey, Lawrence S Honig, Donald Elbert, Randall Bateman, Jeremiah Momper, Ronald G Thomas, Robert A Rissman, Judy Pa and 5 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02925650 (A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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.

NCT02925650 phase1 / phase2completednot on this map

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamic (PD) Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD)

TypeinterventionalSponsorAnnovis Bio Inc.Ran2017 to 2021Enrolled18ConditionsAlzheimer's DiseaseArmsPosiphen, Placebo
3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Douglas GalaskoDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA. dgalasko@health.ucsd.edu.
Martin R FarlowIndiana University, Indianapolis, IN, USA.
Brendan P LuceyWashington University, St Louis, MO, USA.
Lawrence S HonigColumbia University, New York, NY, USA.
Donald ElbertUniversity of Washington, Seattle, WA, USA.
Randall BatemanWashington University, St Louis, MO, USA.
Jeremiah MomperDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.
Ronald G ThomasDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.
Robert A RissmanDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.
Judy PaDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.
Vahan AslanyanUniversity of Southern California, Los Angeles, CA, USA.
Archana BalasubramanianDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.
Tim WestC2N Diagnostics, St Louis, MO, USA.
Maria MaccecchiniAnnovis Bio, Malvern, PA, USA.
Howard H FeldmanDepartment of Neurosciences, UC San Diego, 9444 Medical Center Drive, Suite 1-100, La Jolla, San Diego, CA, 9209, USA.

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark W Bondi · 2019 to 2026
$34.9M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066530
6 · The paper itself

Abstract

backgroundAmyloid beta protein (Aβ) is a treatment target in Alzheimer's Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aβ metabolism using Stable Isotope Labeling Kinetic (SILK) analysis.

methodsDouble-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) confirmed by low CSF Aβ42/40 were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21-23 days, then underwent CSF catheter placement, intravenous infusion of

resultsFrom June 2017 to December 2021, 19 participants were enrolled, randomized within dose cohorts (5 active: 3 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aβ40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs. placebo groups.

conclusionsPosiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects.

trial registrationNCT02925650 on clinicaltrials.gov (registered on 10-24-2016).

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAgedAged, 80 and overAmyloid beta-Protein PrecursorBiomarkersCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMiddle AgedPeptide FragmentsTreatment OutcomeAmyloid beta-Peptidesamyloid beta-protein (1-40)Amyloid beta-Protein PrecursorBiomarkersPeptide FragmentsAlzheimer’s diseaseAmyloid beta proteinAPPClinical trialPharmacodynamics

Identifiers

PMID38970127
PMCPMC11225352

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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.