A Phase 2/3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis

The study is researching an experimental drug called dupilumab. The study is focused on participants with active eosinophilic gastritis (EoG) with or without eosinophilic duodenitis (EoD). Participants with EoD only are not eligible for enrollment. EoG and EoD are uncommon, persistent, allergic/immune diseases in which eosinophils (a type of white blood cell) gather in large numbers in the stomach and small intestine and cause inflammation and damage.
The aim of the study is to evaluate the effect of dupilumab on relieving EoG (with or without EoD) symptoms and reducing inflammation in the stomach and, if applicable, small intestine in adults and adolescents aged 12 years and older, compared to placebo.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug
* How much study drug is in your blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

开始日期2023-05-03

申办/合作机构

Regeneron Pharmaceuticals, Inc.

[+1]

NCT05152563 / Withdrawn临床3期

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of Subcutaneous AK002 in Subjects With Moderate to Severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, and pharmacodynamic effect of subcutaneous lirentelimab (AK002), given monthly for 6 doses, in subjects with moderate to severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis who have an inadequate response with, lost response to, or were intolerant to standard therapies.

开始日期2021-12-01

申办/合作机构

Allakos, Inc.

NCT04856891 / Completed临床3期

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response With, Lost Response to, or Were Intolerant to Standard Therapies

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult patients with active eosinophilic duodenitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.

开始日期2021-05-20

申办/合作机构

Allakos, Inc.

100 项与嗜酸性粒细胞性十二指肠炎相关的临床结果

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100 项与嗜酸性粒细胞性十二指肠炎相关的转化医学

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0 项与嗜酸性粒细胞性十二指肠炎相关的专利（医药）

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项与嗜酸性粒细胞性十二指肠炎相关的文献（医药）

2024-09-01·The Medical journal of Malaysia

Predictors of duodenal eosinophil counts among subjects undergoing diagnostic endoscopy.

Article

作者: Kaur, M ; Braganza, M C ; Ravindran, S ; Mahendra Raj, S ; Hui, L K ; Kunnath, A P

INTRODUCTIONDuodenal eosinophilia has been implicated in the pathophysiology of functional dyspepsia. In a retrospective observational study, we previously reported that duodenal eosinophilia (as defined by a mucosal count of greater than 15 eosinophils per 5 high power fields), was associated with symptomatic erosive gastroesophageal reflux disease (GERD), concomitant co-morbidities and Chinese ethnicity but not functional dyspepsia among 289 multiracial subjects undergoing diagnostic endoscopy in 2019 before the COVID-19 pandemic. We tested the reproducibility of those findings on a larger sample that included the original cohort and another 221 subjects who underwent endoscopy in 2022 after the easing of pandemic restrictions.MATERIALS AND METHODSArchived duodenal histology slides were assessed by a pathologist blind to demographic and clinical data gleamed retrospectively from clinical chart review. Logistic regression analysis was used to explore associations between duodenal eosinophilia and the variables age, gender, ethnicity, year of sampling (2019 vs 2022), concomitant co-morbidities, functional dyspepsia, symptomatic erosive GERD (Los Angeles Grades A to D), endoscopic oesophagitis, gallstone disease, Helicobacter pylori infection, irritable bowel syndrome and NSAID consumption. Three different thresholds for defining duodenal eosinophilia (>15, >22 and >30 eosinophils per 5 high power fields) were tested.RESULTSYear of sampling (2019, pre-pandemic) strongly predicted duodenal eosinophilia across all thresholds (OR 11.76, 13.11 and 21.41 respectively; p = 0.000). The presence of concomitant co-morbidities was a modest predictor across all thresholds whereas Chinese ethnicity only predicted at the lowest threshold. Absolute duodenal eosinophil counts predicted symptomatic erosive GERD (OR 1.03; p = 0.015) but not functional dyspepsia (OR 1.00; p = 0.896) after adjusting for age, gender, ethnicity, concomitant comorbidities and year of endoscopy. None of the subjects reached the threshold for the diagnosis of eosinophilic duodenitis.CONCLUSIONThe cumulative impact of environmental exposures on duodenal eosinophil counts may be much greater than of putative factors linked to functional dyspepsia. A signal linking duodenal eosinophil counts and symptomatic erosive GERD was detected.

2024-08-08·Cureus

Looking Beyond Pneumonia and Asthma in India: An Interesting Case of Churg-Strauss Syndrome

Article

作者: Kumar, Naveen ; Gaba, Manish ; Kumar, Ashok

Churg-Strauss syndrome is a rare multisystem disorder characterized by asthma, eosinophilia, and vasculitis. The patient presented with prolonged fever, cough with blood-stained sputum, weight loss, pain in the abdomen, and a subsequent onset of hoarseness of voice. A history of asthma, left-side vocal cord paralysis, eosinophilia, nodular opacities on radiography, and eosinophilic duodenitis on biopsy led to a diagnosis of Churg-Strauss syndrome. The patient's condition improved on treatment with steroids. This is an interesting case and presents an opportunity to learn about Churg-Strauss syndrome.

2024-06-01·Journal of Allergy and Clinical Immunology

Common and disparate clinical presentations and mechanisms in different eosinophilic gastrointestinal diseases

Review

作者: Shoda, Tetsuo ; Taylor, Richard J ; Rothenberg, Marc E ; Sakai, Naoya

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs.

项与嗜酸性粒细胞性十二指肠炎相关的新闻（医药）

2024-01-16

·BioSpace

Allakos Axes Half of Its Workforce, Drops Lead Inflammatory Candidate

Pictured: Illustration depicting large layoffs/iStock, Andrii Yalanskyi In an effort to cut costs and extend its cash runway, Allakos on Tuesday announced a strategic restructuring initiative that will involve laying off approximately 50% of its employees and focusing its resources on a Phase I candidate. The California-based biotech will also “halt lirentelimab-related activities across clinical, manufacturing, research and administrative functions,” according to Tuesday’s announcement. At the end of 2023, Allakos had $171 million in cash, cash equivalents and investments—and it expects the restructuring program to extend its runway into mid-2026. On Tuesday, alongside the announcement of the strategic restructuring, Allakos reported that lirentelimab failed its Phase II studies in atopic dermatitis and chronic spontaneous urticaria. Allakos’ shares crashed around 61% in premarket trading on Tuesday in response to the announcement, according to Seeking Alpha. Lirentelimab is a humanized IgG1 monoclonal antibody designed to target and activate the Siglec-8 receptor, which is typically found on mature eosinophils and mast cells. When bound by lirentelimab, Siglec-8 exerts its inhibitory effect on several key signaling cascades inside these cells, in turn potentially addressing the underlying pathologies for certain inflammatory diseases, according to the biotech’s website. However, over the years, this mechanism of action has returned mixed results for Allakos. In December 2021, the biotech posted readouts from two studies. In both cases, lirentelimab hit one of its co-primary endpoints but missed the other. In the Phase III ENIGMA 2 study, the anti-Siglec-8 antibody induced statistical histological improvements but failed to significantly ease symptom burden in patients with eosinophilic gastritis and/or eosinophilic duodenitis. The Phase II/III KRYPTOS trial in eosinophilic esophagitis returned similarly confusing data, with lirentelimab acing its histologic endpoint but not its symptomatic targets. With lirentelimab’s discontinuation, Allakos will now focus its effort and resources on Phase I candidate AK006, another investigational humanized IgG1 monoclonal antibody. AK006 targets Siglec-6, which functions similarly to Siglec-8 but is exclusively found on mast cells. AK006 is currently in a Phase I study in healthy volunteers, for which the biotech aims to complete its single- and multiple-ascending dose cohorts in the first quarter of 2024. Allakos is also eyeing a Phase I trial of intravenous AK006 in chronic spontaneous urticaria. The biotech is planning to launch the study in the second quarter of 2024 and report topline data by year-end, according to its Tuesday’s announcement. The company’s reduction in workforce continues an industry layoff trend in 2023, in which more than 120 public biotechs terminated upwards of 10,000 jobs, according to an analysis by BioPharma Dive. But there is reason for the sector to be more upbeat this year. At last week's 42nd annual J.P. Morgan Healthcare Conference, experts pointed to signs of life in biopharma on the investment side and expressed cautious optimism overall for 2024. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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