Evidence map›Paper›PMID 35098554›Full record

Trial reportMuscle & nerve2022

Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses.

Robert G Miller, Rongzhen Zhang, Paige M Bracci, Ari Azhir, Richard Barohn, Richard Bedlack, Michael Benatar, James D Berry, Merit Cudkowicz, Edward J Kasarskis and 6 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Muscle & nerve, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 6% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

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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

16 authors at 12 institutions in 1 country.

Robert G MillerCalifornia Pacific Medical Center, San Francisco, California, USA.
Rongzhen ZhangDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Ari AzhirNeuvivo, Inc., Palo Alto, California, USA.
Richard BarohnUniversity of Missouri, Columbia, Missouri, USA.
Richard BedlackDuke University Medical Center, Durham, North Carolina, USA.
Michael BenatarUniversity of Miami Miller School of Medicine, Miami, Florida, USA.
James D BerryMassachusetts General Hospital, Boston, Massachusetts, USA.
Merit CudkowiczMassachusetts General Hospital, Boston, Massachusetts, USA.
Edward J KasarskisUniversity of Kentucky, Lexington, Kentucky, USA.
Hiroshi MitsumotoColumbia University Medical Center, New York, New York, USA.
Georgios ManousakisUniversity of Minnesota Medical School, Minneapolis, Minnesota, USA.
David WalkUniversity of Minnesota Medical School, Minneapolis, Minnesota, USA.
Bjorn OskarssonDepartment of Neurology, Mayo Clinic, Florida, USA.
Jeremy ShefnerBarrow Neurological Institute, University of Arizona College of Medicine Phoenix, Creighton University College of Medicine Phoenix, Phoenix, Arizona, USA.
Michael S McGrathDepartment of Medicine, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-7232-2602
University of California, San Francisco · USMassachusetts General Hospital · USUniversity of Minnesota Medical Center · USCalifornia Pacific Medical Center · USColumbia University Irving Medical Center · USCreighton University · USDuke Medical Center · USMayo Clinic in Florida · USNeoGenomics (United States) · USUniversity of Kentucky · USUniversity of Miami · USUniversity of Missouri · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION/

aimsALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.

methodsThe phase 2B trial enrolled 138 participants within 3 y of symptom onset and with plasma hs-CRP values >1.13 mg/L. They were randomized 1:1 to receive either placebo or NP001 for 6 mo. Change from baseline ALSFRS-R scores was the primary efficacy endpoint. Secondary endpoints included vital capacity (VC) change from baseline and percentage of participants showing no decline of ALSFRS-R score over 6 mo (non-progressor).

resultsThe phase 2B study did not show significant differences between placebo and active treatment with respect to change in ALSFRS-R scores, or VC. The drug was safe and well tolerated. A post hoc analysis identified a 40- to 65-y-old subset in which NP001-treated patients demonstrated slower declines in ALSFRS-R score by 36% and VC loss by 51% compared with placebo. A greater number of non-progressors were NP001-treated compared with placebo (p = .004). DISCUSSION: Although the phase 2B trial failed to meet its primary endpoints, post hoc analyses identified a subgroup whose decline in ALSFRS-R and VC scores were significantly slower than placebo. Further studies will be required to validate these findings.

Indexed as

Amyotrophic Lateral SclerosisBiomarkersC-Reactive ProteinDisease ProgressionDouble-Blind MethodHumansVital CapacityBiomarkersC-Reactive Proteinamyotrophic lateral sclerosis (ALS)C-reactive protein (CRP)inflammationNP001respiratory function

Identifiers

PMID35098554
PMCPMC9327716
OpenAlexW4210693756

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.