Evidence map›Paper›PMID 32568196›Full record

Trial reportJournal of Alzheimer's disease : JAD2020

Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks.

Heather Guthrie, Lawrence S Honig, Helen Lin, Kaycee M Sink, Kathleen Blondeau, Angelica Quartino, Michael Dolton, Montserrat Carrasco-Triguero, Qinshu Lian, Tobias Bittner and 3 more

Registry-linked trialAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02353598 (A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
–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.

NCT02353598 phase1completednot on this map

A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorGenentech, Inc.Ran2015 to 2019Enrolled77ConditionsAlzheimer DiseaseArmsCrenezumab dose level 1, Crenezumab dose level 2, Crenezumb dose level 3, Placebo
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

13 authors.

Heather GuthrieGenentech, Inc., South San Francisco, CA, USA.
Lawrence S HonigColumbia University Irving Medical Center, New York, NY, USA.
Helen LinGenentech, Inc., South San Francisco, CA, USA.
Kaycee M SinkGenentech, Inc., South San Francisco, CA, USA.
Kathleen BlondeauF. Hoffmann-La Roche Ltd, Basel, Switzerland.
Angelica QuartinoGenentech, Inc., South San Francisco, CA, USA.
Michael DoltonGenentech, Inc., South San Francisco, CA, USA.
Montserrat Carrasco-TrigueroGenentech, Inc., South San Francisco, CA, USA.
Qinshu LianGenentech, Inc., South San Francisco, CA, USA.
Tobias BittnerF. Hoffmann-La Roche Ltd, Basel, Switzerland.
David ClaytonGenentech, Inc., South San Francisco, CA, USA.
Jillian SmithF. Hoffmann-La Roche Ltd, Welwyn Garden City, UK.
Susanne OstrowitzkiGenentech, Inc., South San Francisco, CA, USA.

Funding

Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1M
NIA NIH HHS P30 AG066462NIA NIH HHS P50 AG008702
6 · The paper itself

Abstract

backgroundCrenezumab is a fully humanized, monoclonal anti-amyloid-β immunoglobulin G4 antibody.

objectiveThis Phase Ib study (NCT02353598) evaluated the safety, tolerability, and pharmacokinetics of crenezumabat doses of ≤120 mg/kg administered intravenously every 4 weeks (q4w). Immunogenicity and exploratory biomarkers were also evaluated.

methodsIn this multicenter, double-blind study, participants (aged 50-90 years) with mild-to-moderate Alzheimer's disease (AD) and amyloid-positive positron emission tomography (PET) scan were randomized to receive crenezumab 30 or 45 mg/kg (Cohort 1, n = 21), 60 mg/kg (Cohort 2, n = 21), or 120 mg/kg (Cohort 3, n = 19) or corresponding placebo (n = 14) intravenously q4w for 13 weeks. Seventy-one participants were subsequently enrolled in an optional open-label extension (OLE) and received crenezumab at the originally assigned dose level, except for Cohort 3 (crenezumab 60 mg/kg during OLE). Participants received regular brain MRIs to assess amyloid-related imaging abnormalities (ARIA). Results up to Week 133 are reported.

resultsApproximately 94% of participants experienced ≥1 adverse event (AE). Most AEs were mild or moderate; 15.5% experienced a Grade ≥3 AE. No ARIA-edema/effusion (ARIA-E) events were observed. New ARIA-micro hemorrhages and hemosiderosis (ARIA-H) were reported in 4.9% (double-blind treatment period) and 9.9% (combined double-blind treatment and OLE periods) of participants. Steady-state trough concentrations of crenezumab were dose-proportional and maintained for each dose level.

conclusionCrenezumab doses of ≤120 mg/kg intravenously q4w were well tolerated. The observed safety profile for ≤133 weeks of treatment in a mild-to-moderate AD population was similar to that seen in previous trials.

Indexed as

Treatment OutcomeAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkersBrainDouble-Blind MethodFemaleHumansMaleMiddle AgedNeuroimagingAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkerscrenezumabAlzheimer’s diseaseamyloid positron emission tomographyamyloid-β peptidecrenezumabhumanized monoclonal antibodyinfusion site adverse eventmagnetic resonance imagingsafety

Identifiers

PMID32568196
PMCPMC7505005

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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.