Surfaxin (lucinactant) / Windtree Therap, Esteve - LARVOL DELTA

The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Windtree Therapeutics | Recruiting ➔ Completed

Trial completion • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: Windtree Therapeutics; Trial completion date: Aug 2021 ➔ Nov 2021; Trial primary completion date: Jul 2021 ➔ Nov 2021

Clinical • Trial completion date • Trial primary completion date • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • PCR

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke. (PubMed, Environ Res) - "PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs."

Journal • Preclinical • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CRP • TJP1

Trials for second generation Covid-19 vaccines: Revisiting the debate over placebo use in developing country clinical trials. (PubMed, Indian J Med Ethics) - "Compared to the earlier zidovudine and Surfaxin trials, Covid-19 vaccine trials are likely to confer lower risk to placebo groups and to offer a greater number and variety of alternative study designs. However, the advent of variants that may create genuine uncertainty as to comparator vaccine effectiveness could justify a placebo control, depending on vaccine characteristics, variant prevalence, the degree of variant resistance, and the acceptability of immune-bridging studies. These factors must be considered together in the necessary case-by-case assessment of the ethical justification for any proposed trial."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease

The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P1/2; N=30; Not yet recruiting; Sponsor: Windtree Therapeutics

Clinical • New P1/2 trial • Acute Lung Injury • Acute Respiratory Distress Syndrome • Novel Coronavirus Disease • Respiratory Diseases • PCR

The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) (clinicaltrials.gov) - P2; N=20; Recruiting; Sponsor: Windtree Therapeutics; Not yet recruiting ➔ Recruiting; Phase classification: P1/2 ➔ P2

Enrollment open • Phase classification • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR

A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks GA (clinicaltrials.gov) - P2; N=12; Suspended; Sponsor: Windtree Therapeutics; N=90 ➔ 12; Recruiting ➔ Suspended

Clinical • Enrollment change • Trial suspension • Acute Respiratory Distress Syndrome • Respiratory Diseases

The Safety and Preliminary Efficacy of Lucinactant in Adults With COVID-19 (clinicaltrials.gov) - P1/2; N=30; Not yet recruiting; Sponsor: Windtree Therapeutics; Trial completion date: Nov 2020 ➔ Apr 2021; Initiation date: Jun 2020 ➔ Oct 2020; Trial primary completion date: Oct 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks GA (clinicaltrials.gov) - P2; N=90; Recruiting; Sponsor: Windtree Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Respiratory Distress Syndrome • Respiratory Diseases

Radiation Mitigating Properties of Intranasally Administered Kl4 Surfactant in a Murine Model of Radiation-Induced Lung Damage. (PubMed, Radiat Res) - "...In this study, KL4 surfactant (lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage...The results of this study showed that intranasal delivery of KL4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF, as were plasma pro-inflammatory cytokine levels and biomarker of oxidative stress. KL4 surfactant is a promising MCM for mitigation of lung tissue damage after targeted, thoracic irradiation and has the potential to be developed as a broad-spectrum, multi-use MCM against chemical, biological, radiological or nuclear threat agents with potential to cause lung injury."

Biomarker • Journal • Biosimilar • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

Using FRET to elucidate the lipid trafficking mechanism of SP-Bc and N terminal peptides in comparison with KL4 (ACS-Sp 2020) - "A decrease in FRET among the studied peptides will indicate increased rates of membrane fusion and may reveal a selective interaction with certain LS lipids. Current data displays a decrease in FRET within the DPPC:POPG SP-Bc system which supports previous NMR studies that showed the peptide selectively interacts with DPPC-rich liposomes and may indicate that SP-Bc facilitates membrane fusion events, which is a proposed mechanism of lipid trafficking at the air-fluid interface."

A Randomized, Controlled Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks GA (clinicaltrials.gov) - P2; N=90; Not yet recruiting; Sponsor: Windtree Therapeutics

Clinical • New P2 trial

Deposition of Aerosolized Lucinactant in Nonhuman Primates. (PubMed, J Aerosol Med Pulm Drug Deliv) - "Lucinactant for inhalation is an investigational noninvasive, aerosolized surfactant replacement therapy for treatment of preterm neonates with respiratory distress syndrome. Aerosolized lucinactant, delivered using the ADS via constant flow nCPAP, is deposited in all regions of the lungs demonstrating that surfactant can be aerosolized and delivered noninvasively to NHPs."

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Using FRET to elucidate the lipid trafficking mechanism of SP-Bc terminal peptide in comparison with KL4 (ACS-Sp 2019) - "...SP-Bc, is examined in comparison to its synthetic mimic, KL4, which is the main ingredient of a surfactant replacement known as Surfaxin...The presence of this peak may be indicative of the location of the NBD probe in the bilayer or reveal differences between the KL4 and SP-B membrane environments. Current data displays a decrease in FRET within the DPPC:POPG KL4 system which supports previous NMR studies that showed the peptide selectively interacts with DPPC-rich liposomes and may indicate that KL4 facilitates membrane fusion events, which is a proposed mechanism of lipid trafficking at the air-fluid interface."

Surfactants preparations for preterm infants with respiratory distress syndrome: past, present, and future. (PubMed, Korean J Pediatr) - "...Lucinactant, a second-generation synthetic surfactant containing analog of SP-B, was better or at least as effective as natural surfactant, suggesting that lucinactant could be used as an alternative to natural surfactants...The more important thing than the preparation of surfactant to improve the outcome is the timing and the mode of administration of surfactant. A new synthetic surfactant containing synthetic phospholipid incorporated with analogues of SP-B and SP-C will be a potential alternative to natural surfactants in the coming years and treatment modality such as less-invasive method or non-invasive method of surfactant administration will be the most important task to be solved."

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