Evidence map›Paper›PMID 34389633›Full record

Trial reportBMJ open gastroenterology2021

A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis.

Kathy Weisel, Nicola Scott, Scott Berger, Susanne Wang, Kurt Brown, Marcy Powell, Matthijs Broer, Clarissa Watts, Debra J Tompson, Susan W Burriss and 3 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in BMJ open gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02903966 (A Multicentre, Randomised, Double-blind), which is not on this map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
8.4field-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.

NCT02903966 phase2completednot on this map

A Multicentre, Randomised, Double-blind (Sponsor Unblinded), Placebo-controlled Study With Open Label Extension to Investigate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2982772 in Subjects With Active Ulcerative Colitis

TypeinterventionalSponsorGlaxoSmithKlineRan2016 to 2019Enrolled36ConditionsColitis, UlcerativeArmsGSK2982772, Placebo
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 86 citations in OpenAlex.

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  7. Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026
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2 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 3 countries.

Kathy WeiselImmunology and Inflammation, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Nicola ScottBiostatistics, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK.
Scott BergerImmunology and Inflammation, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Susanne WangImmunology and Inflammation, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Kurt BrownImmunology and Inflammation, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Marcy PowellSafety and Medical Governance, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Matthijs BroerGlobal Clinical Development, GlaxoSmithKline, Van Asch van Wijckstraat, LP Amersfoort, The Netherlands.
Clarissa WattsGlobal Clinical Sciences and Delivery, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK.
Debra J TompsonClinical Pharmacology Modelling and Simulation, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK.
Susan W BurrissGlobal Clinical Sciences and Delivery, GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Simon HawkinsGlobal Clinical Sciences and Delivery, GlaxoSmithKline, Brentford, Middlesex, UK.
Kathy Abbott-BannerDiscovery Medicine, GlaxoSmithKline, Brentford, Middlesex, UK kathy.x.abbott-banner@gsk.com.ORCID 0000-0003-1470-7368
Paul Peter TakPharmaceuticals Research and Development, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK.
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USGlaxoSmithKline (Netherlands) · NLResearch Triangle Park Foundation · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.

designIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.

resultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.

conclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC. TRIAL REGISTRATION NUMBER: NCT02903966.

Indexed as

Colitis, UlcerativeOxazepinesHumansQuality of LifeReceptor-Interacting Protein Serine-Threonine KinasesTriazolesGSK2982772OxazepinesReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanTriazolescolonic diseasesinflammatory bowel diseasepharmacokineticsTNFulcerative colitis

Identifiers

PMID34389633
PMCPMC8365785
OpenAlexW3187146563

What OpenQuestion holds

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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.