ordesekimab (AMG 714) / Amgen, Sanofi - LARVOL DELTA

New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review. (PubMed, Healthcare (Basel)) - "For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent...Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated...For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments...Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric..."

Journal • Review • Autoimmune Hepatitis • Celiac Disease • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Hepatitis B • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Transplantation • IL13 • IL5 • TGM2 • TSLP

PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2 | N=226 | Completed | Sponsor: Provention Bio, a Sanofi Company | Active, not recruiting ➔ Completed

Trial completion • Celiac Disease • Immunology

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | Phase classification: P2a ➔ P2 | Trial completion date: Sep 2024 ➔ May 2025

Enrollment closed • Phase classification • Trial completion date • Dermatology • Immunology • Vitiligo

PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2 | N=226 | Active, not recruiting | Sponsor: Provention Bio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Celiac Disease • Immunology

PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: Provention Bio, Inc. | Phase classification: P2b ➔ P2 | Trial completion date: Dec 2023 ➔ Aug 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Phase classification • Trial completion date • Trial primary completion date • Celiac Disease • Immunology

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a | N=57 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2024 ➔ Sep 2024 | Trial primary completion date: Mar 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Dermatology • Solid Tumor • Vitiligo

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a | N=57 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2023 ➔ Mar 2024 | Trial primary completion date: Oct 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Dermatology • Vitiligo

LONG-TERM FOLLOW-UP OF PATIENTS WITH TYPE 2 REFRACTORY CELIAC DISEASE TREATED WITH AMG 714, AN ANTI-INTERLEUKIN 15 MONOCLONAL ANTIBODY, AT GEORGES POMPIDOU HOSPITAL (UEGW 2022) - "After the trial, one patient was treated with chemotherapy and autologous stem cell transplantation, and one patient reintroduced open-capsule budesonide.  5-year follow-up data shows clinical remission in all patients treated with AMG-714, mucosal recovery and improvement in clonality in most cases. It will be interesting to collect follow-up data from all centers who participated in this trial. Our results suggest that further research of AMG-714 in RCD 2 is warranted."

Clinical • Bone Marrow Transplantation • Celiac Disease • Hematological Malignancies • Immunology • Lymphoma • Oncology • Small Intestinal Carcinoma • T Cell Non-Hodgkin Lymphoma • Transplantation • IL15

Strategies to evaluate potential effector function of glycan variants: a case study of ordesekimab (AMG 714 or PRV-015). (PubMed, J Immunotoxicol) - "In addition, in vitro peripheral blood mononuclear cells-based ADCC assay did not reveal any cytolytic effect of ordesekimab with various levels of HM content when cocultured with recombinant human IL-15. Taken together, these data demonstrate that ADCC is not a potential liability for ordesekimab and does not contribute to the reduction of IL-15-mediated inflammation, the intended pharmacological effect."

Journal • Celiac Disease • Immunology • Inflammation

PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2b | N=220 | Recruiting | Sponsor: Provention Bio, Inc. | Trial completion date: Jul 2022 ➔ Dec 2023 | Trial primary completion date: Jul 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Celiac Disease • Immunology

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a; N=57; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Dec 2022 ➔ Mar 2023; Trial primary completion date: Jun 2022 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Dermatology • Vitiligo

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a; N=57; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dermatology • Vitiligo

PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2b; N=220; Recruiting; Sponsor: Provention Bio, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Celiac Disease • Immunology

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a; N=57; Not yet recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Aug 2022 ➔ Dec 2022; Initiation date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Mar 2022 ➔ Jun 2022

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Dermatology • Dermatopathology • Vitiligo

Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study. (PubMed, Lancet Gastroenterol Hepatol) - P2a | "In patients with refractory coeliac disease type 2 who were treated with AMG 714 or placebo for 10 weeks, there was no difference between the groups in terms of the primary endpoint of aberrant intraepithelial lymphocyte reduction from baseline. Effects on symptoms and other endpoints suggest that further research of AMG 714 may be warranted in patients with refractory coeliac disease type 2."

Clinical • Journal • P2a data • Celiac Disease • Immunology

Safety and efficacy of AMG 714 in adults with coeliac disease exposed to gluten challenge: a phase 2a, randomised, double-blind, placebo-controlled study. (PubMed, Lancet Gastroenterol Hepatol) - P2a | "The primary endpoint, change in VHCD ratio from baseline after 12 weeks of treatment in patients with coeliac disease undergoing gluten challenge, was not significantly different between placebo and AMG 714 at either 150 mg or 300 mg. Effects on intraepithelial lymphocyte density and symptoms suggest that further research of AMG 714 may be warranted in patients with non-responsive coeliac disease."

Clinical • Journal • P2a data • Celiac Disease • Gastrointestinal Disorder

PROACTIVE: PRV-015 in Gluten-free Diet Non-responsive Celiac Disease (clinicaltrials.gov) - P2b; N=220; Not yet recruiting; Sponsor: Provention Bio, Inc.

Clinical • New P2b trial • Celiac Disease • Immunology

REVEAL: Evaluation of AMG 714 for Vitiligo (clinicaltrials.gov) - P2a; N=57; Not yet recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Clinical • New P2a trial