acebilustat (CTX-4430) / Celtaxsys - LARVOL DELTA

HEAL: Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Stanford University | Recruiting ➔ Active, not recruiting | N=70 ➔ 40 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial primary completion date • Inflammation

HEAL: Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Stanford University | Trial primary completion date: Feb 2024 ➔ Feb 2025

Trial primary completion date • Inflammation

Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease. (PubMed, Curr Opin Cardiol) - "Despite a growing body of evidence, current literature demonstrates a persistent gap in the number of known genes responsible for lymphatic disease entities. Recent clinical classification tools have been introduced in order to integrate traditional symptom- and time-based diagnostic approaches with modern genetic classifications, as highlighted in the updated St. George's classification system. With the introduction of this novel approach, clinicians may be better equipped to recognize established disease and, potentially, to identify novel causal mutations. Further research is needed to identify additional genetic causes of disease and to optimize current clinical tools for diagnosis and treatment."

Journal • EPHB4

Lymphedema Dermal Ultrasonography: Evaluation of Dermal and Sub-dermal Dimensions, Subcomponents, and Echogenicity (UIP-AVLS 2023) - P2 | "The HEAL (Human Upper Extremity Acebilustat Lymphedema) trial (NCT05203835) is investigating the ability of leukotriene B4 (LTB4) antagonism to heal the structural damage caused by chronic lymphedema... All measured variables, with the exception of epidermal echogenicity, demonstrated statistically significant differences between the lymphedema arm and the normal arm (Table 1). As expected, the dermal thickness of the lymphedema arm was increased compared to the normal arm (p < 0.001). These subcomponents of the dermis were each individually increased compared to the normal limb."

Inflammation

A Selective Leukotriene B4 Antagonist, Acebilustat, for Treatment of Outpatients With COVID-19 Disease: A Randomized, Double-blind, Placebo-controlled Phase 2 Trial (ATS 2023) - "Treatment with the LTB4 antagonist acebilustat did not shorten duration of symptoms in low-risk outpatients with COVID-19 infection. Despite being highly vaccinated, patients experienced substantial and prolonged symptoms of COVID-19 in both study arms. Future outpatient trials in COVID-19 should consider incorporating both severity and duration of symptoms to accurately reflect disease burden."

Clinical • P2 data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Multi-walled carbon nanotubes induce arachidonate 5-lipoxygenase expression and enhance the polarization and function of M1 macrophages in vitro. (PubMed, Nanotoxicology) - "The cell-free media from MWCNT-polarized macrophages induced the migration of neutrophilic cells (differentiated from HL-60), which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, an LTB4 receptor antagonist, but not NS-398, a cyclooxygenase 2 inhibitor, revealing LTB4 as a major mediator of neutrophil chemotaxis from MWCNT-polarized macrophages. Knockdown of Alox5 using specific small hairpin-RNA suppressed MWCNT-induced M1 polarization, LTB4 secretion, and migration of neutrophils. Taken together, these findings demonstrate the polarization of M1 macrophages by Mitsui-7 MWCNTs in vitro and that induction of Alox5 is an important mechanism by which the MWCNTs promote proinflammatory responses by boosting M1 polarization and production of proinflammatory LMs."

Journal • Preclinical • Inflammation • Oncology • Pneumonia • ALOX5 • CD68 • IL1B • TNFA

Evaluation of acebilustat, a selective inhibitor of leukotriene B4 biosynthesis, for treatment of outpatients with mild-moderate COVID-19 disease: A randomized, double-blind, placebo- controlled Phase 2 trial. (PubMed, Clin Infect Dis) - "Sustained symptoms through Day 28 were common in this low-risk population. Despite this, LTB4 antagonism with acebilustat did not shorten symptom duration in outpatients with COVID-19."

Clinical • Journal • P2 data • Infectious Disease • Inflammation • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2 | N=122 | Completed | Sponsor: Stanford University | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2 | N=120 | Completed | Sponsor: Stanford University | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis. (PubMed, J Cyst Fibros) - "Acebilustat did not improve lung function. A trend towards reduced pulmonary exacerbations in subjects with an earlier stage of lung disease suggests a potential effect in this population."

Clinical • Journal • P2 data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Stanford University | Trial completion date: Jul 2022 ➔ Jan 2023

Trial completion date • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2 | N=122 | Active, not recruiting | Sponsor: Stanford University | Recruiting ➔ Active, not recruiting | N=240 ➔ 122 | Trial completion date: Aug 2022 ➔ Jan 2023 | Trial primary completion date: Aug 2022 ➔ May 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

HEAL: Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting

Enrollment open • Inflammation

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Stanford University | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Stanford University | Trial primary completion date: Aug 2022 ➔ May 2022

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

HEAL: Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Stanford University | Initiation date: Feb 2022 ➔ May 2022

Trial initiation date • Inflammation

HEAL: Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (clinicaltrials.gov) - P2; N=70; Not yet recruiting; Sponsor: Stanford University

New P2 trial • Inflammation

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: Stanford University; Trial completion date: Mar 2022 ➔ Aug 2022; Trial primary completion date: Mar 2022 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Stanford University; Trial completion date: Mar 2022 ➔ Aug 2022; Trial primary completion date: Mar 2022 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Stanford University; Enrolling by invitation ➔ Recruiting

Clinical • Enrollment status • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: Stanford University; Enrolling by invitation ➔ Recruiting

Clinical • Enrollment status • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2; N=120; Enrolling by invitation; Sponsor: Stanford University; Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2; N=240; Enrolling by invitation; Sponsor: Stanford University; Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol (clinicaltrials.gov) - P2; N=240; Not yet recruiting; Sponsor: Stanford University

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease

COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol (clinicaltrials.gov) - P2; N=120; Not yet recruiting; Sponsor: Stanford University

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease