Evidence map›Paper›PMID 24873720›Full record

Trial reportThe Lancet. Neurology2014

Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.

Adam L Boxer, Anthony E Lang, Murray Grossman, David S Knopman, Bruce L Miller, Lon S Schneider, Rachelle S Doody, Andrew Lees, Lawrence I Golbe, David R Williams and 21 more

6 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 157 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed, 3 pooled it
37.9field-weighted citation impact, top 1% 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.

NCT01110720 phase2 / phase3completednot on this map

A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy

TypeinterventionalSponsorAllon TherapeuticsRan2010 to 2012Enrolled313ConditionsProgressive Supranuclear PalsyArmsDavunetide, Placebo
NCT02365922 completednot on this map

Rare Diseases Clinical Research Network Advancing Research and Treatment for Frontotemporal Lobar Degeneration [ARTFL]: Research Projects 1 & 2

TypeobservationalSponsorUniversity of California, San FranciscoRan2014 to 2020Enrolled1,489ConditionsFTLD, Progressive Supranuclear Palsy (PSP), Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD)
NCT02422485 phase1completednot on this mapstarted 2015, after this paper: background citation

A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

TypeinterventionalSponsorAdam BoxerRan2015 to 2019Enrolled10ConditionsProgressive Supranuclear PalsyArmsSalsalate
NCT02460731 phase1completednot on this mapstarted 2015, after this paper: background citation

A 6 Month, Open-Label, Pilot Futility Clinical Trial of Monthly Young Healthy Male Donor Plasma Transfusions for Progressive Supranuclear Palsy

TypeinterventionalSponsorUniversity of California, San FranciscoRan2015 to 2019Enrolled6ConditionsProgressive Supranuclear PalsyArmsFresh Frozen Plasma
NCT02494024 phase1completednot on this mapstarted 2015, after this paper: background citation

A Double-Blind, Placebo Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy

TypeinterventionalSponsorC2N DiagnosticsRan2015 to 2016Enrolled32ConditionsProgressive Supranuclear PalsyArmsSingle dose C2N-8E12, Single dose placebo
NCT02966145 completednot on this mapstarted 2016, after this paper: background citation

The Four-Repeat Tauopathy Neuroimaging Initiative

TypeobservationalSponsorUniversity of California, San FranciscoRan2016 to 2024Enrolled293ConditionsCorticobasal Degeneration (CBD), Corticobasal Syndrome (CBS), Cortical-basal Ganglionic Degeneration (CBGD), Progressive Supranuclear Palsy (PSP)ArmsObservational Study
3 · Its place in the literature

Who cites it

157 citing papers in PubMed, 3 syntheses or guidelines pooled it, 282 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Longitudinal cognitive outcomes in two progressive supranuclear palsy clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Trial
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  10. Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials.Movement disorders : official journal of the Movement Disorder Society · 2017
    Trial
  11. Minimal clinically important worsening on the progressive supranuclear Palsy Rating Scale.Movement disorders : official journal of the Movement Disorder Society · 2016
    Trial
  12. Trial
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  15. Article
  16. Review
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  20. Article

97 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 20 institutions in 7 countries.

Adam L BoxerMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: aboxer@memory.ucsf.edu.
Anthony E LangDepartment of Neurology, University of Toronto, Toronto, ON, Canada.
Murray GrossmanDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Bruce L MillerMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Lon S SchneiderDepartment of Psychiatry and the Behavioural Sciences and Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Rachelle S DoodyDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.
Andrew LeesInstitute of Neurology, University College London, UK.
Lawrence I GolbeDepartment of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
David R WilliamsFaculty of Medicine, Monash University, Melbourne, VIC, Australia.
Jean-Cristophe CorvolAssistance Publique-Hôpitaux de Paris, INSERM, CIC1422 and UMRS1027, Sorbonne Universités, Université Pierre et Marie Curie, Paris, France; Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
Albert LudolphDepartment of Neurology, University Hospital, Ulm, Germany.
David BurnInstitute for Ageing and Health, Newcastle University, Newcastle, UK.
Stefan LorenzlInterdisciplinary Center for Palliative Medicine, Munich University Hospital-Klinikum Grosshadern, Munich, Germany.
Irene LitvanDepartment of Neurology, University of California, San Diego, CA, USA.
Erik D RobersonDepartment of Neurology, University of Alabama, Birmingham, AL, USA.
Günter U HöglingerDepartment of Translational Neurodegeneration, Technical University Munich, Munich, Germany.
Mary KoestlerMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Viviana Van DeerlinDepartment of Neurology and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Christopher RandolphDepartment of Neurology, Loyola University School of Medicine, Chicago, IL, USA.
Iryna V LobachMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Hilary W HeuerMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Illana GozesDepartment of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel.
Lesley ParkerTekmira Pharmaceuticals, Burnaby, BC, Canada.
Steve WhitakerOmeros, Seattle, WA, USA.
Joe HirmanPacific Northwest Statistical Consulting, Woodinville, WA, USA.
Alistair J StewartPaladin Laboratories, St Laurent, QC, Canada.
Michael GoldUCB BioSciences, Research Triangle Park, NC, USA.
Bruce H MorimotoCelerion, Lincoln, NE, USA.
AL-108-231 Investigators
University of California, San Francisco · USMayo Clinic in Arizona · USUniversity Memory and Aging Center · USUniversity of Pennsylvania · USArbutus Biopharma (Canada) · CABaylor College of Medicine · USCelerion (United States) · USJohnson University · USLoyola University Chicago · USMonash University · AUNewcastle University · GBOmeros Corporation (United States) · USPaladin Labs (Canada) · CAPitié-Salpêtrière Hospital · FRTechnical University of Munich · DETel Aviv University · ILTriangle · USUniversity College London · GBUniversity Hospital Ulm · DEUniversity of Alabama at Birmingham · US

Funding

VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARANDA, MARIA P. · 1985 to 2019
$41.0M
Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
The Four Repeat Tauopathy Neuroimaging InitiativeR01AG038791 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L. · 2010 to 2020
$18.1M
NIA NIH HHS P01 AG017586NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG038791
6 · The paper itself

Abstract

backgroundIn preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP.

methodsIn a double-blind, parallel group, phase 2/3 trial, participants were randomly assigned with permuted blocks in a 1:1 ratio to davunetide (30 mg twice daily, intranasally) or placebo for 52 weeks at 48 centres in Australia, Canada, France, Germany, the UK, and the USA. Participants met the modified Neuroprotection and Natural History in Parkinson Plus Syndrome study criteria for PSP. Primary endpoints were the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England Activities of Daily Living (SEADL) scale at up to 52 weeks. All participants and study personnel were masked to treatment assignment. Analysis was by intention to treat. The trial is registered with Clinicaltrials.gov, number NCT01110720.

findings313 participants were randomly assigned to davunetide (n=157) or to placebo (n=156), and 241 (77%) completed the study (118 and 156 in the davunetide and placebo groups, respectively). There were no differences in the davunetide and placebo groups in the baseline PSPRS and SEADL. The davunetide and placebo groups did not differ in the change from baseline in PSPRS (median 11·8 [95% CI 10·5 to 13·0] vs 11·8 [10·5 to 13·0], respectively, p=0·41) or SEADL (-0·20 [-0·20 to -0·17] vs -0·20 [-0·22 to -0·17], respectively, p=0·92). 54 serious adverse events were reported in each of the treatment groups, including 11 deaths in the davunetide group and ten in the placebo group. The frequency of nasal adverse events was greater in the davunetide group than in the placebo group (epistaxis 18 [12%] of 156 vs 13 [8%] of 156, rhinorrhoea 15 [10%] vs eight [5%], and nasal discomfort 15 [10%] vs one [<1%]).

interpretationDavunetide is not an effective treatment for PSP. Clinical trials of disease-modifying treatment are feasible in patients with PSP and should be pursued with other promising tau-directed treatments.

fundingAllon Therapeutics.

Indexed as

AgedDouble-Blind MethodFemaleHumansMaleOligopeptidesSupranuclear Palsy, ProgressiveTreatment OutcomedavunetideOligopeptides

Identifiers

PMID24873720
PMCPMC4129545
OpenAlexW2129669150

What OpenQuestion holds

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Read underepoch 390

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.