Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age.

BACKGROUND: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions. METHODS: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. RESULTS: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. CONCLUSIONS: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05590403.

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.

BACKGROUND: The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo. OBJECTIVES: A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143). METHODS: Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0.5 to 40 mg) were tested under fasted and fed (10 mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30 mg) were administered once daily for 7 days in three sequential cohorts. RESULTS: No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events. Alpibectir showed rapid absorption after single dose (mean Tmax range of 0.88 to 1.53 h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3.87 h), a lower Cmax (-17.7%) and increased AUC0-t (+19.6%) compared with the fasted condition. Following repeat dosing, dose proportionality was shown for both Cmax and AUC0-tau. Accumulation of alpibectir was observed across all doses, with a more profound effect on AUC during a dosing interval (AUC0-tau) compared with Cmax (1.8- and 1.3-fold on average), respectively. Steady state was considered to have been achieved by Day 7 of dosing. CONCLUSIONS: Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food.

Benefits of the application of heat and pressure on peripheral venous cannulation in adults: A randomized controlled trial.

AIM: To evaluate the effectiveness of the application of topical heat, high pressure or a combination of both on antebrachial venous cannulation. DESIGN: A cross-over clinical trial blinded for haemolysis analysis. METHODS: This cross-over clinical trial with two periods was performed in the Clinical Trial Unit of Hospital Universitario de La Princesa (Madrid) during June-July of 2017 in 59 healthy adults who were randomly allocated to one of three interventions: (1) Using dry topical heat for 7 min produced by two hot seed bags (N = 21), (2) Applying controlled pressure from a sphygmomanometer inflated to 100 mmHg (N = 18) and (3) combining heat and pressure (N = 20) in one period out of two. All interventions were contrasted to standard clinical practice in the other period. The comparator involved a standard tourniquet around the upper arm to restrict venous blood flow. The primary outcome was effectiveness measured as vein cannulation at first attempt. Secondary outcomes were vein perception, pain, haemolysis in blood samples and adverse events. RESULTS: All the interventions were more effective than comparator. Vein perception was optimized in about all individuals. Moreover, pain relief was significantly higher when high pressure was applied. Haemolysis was not affected in any of the three interventions. In addition, no serious adverse events appeared. CONCLUSION: High pressure is determined to be the most effective in vein catheterization, pain relief, vein perception and quality of blood sample inalterability. Moreover, it is safe considering that only one adverse event appeared. IMPACT: Vein cannulation is a very common invasive technique, where repeated failures have been registered. Thus, we consider it relevant to develop interventions to achieve venous catheterization at first attempt to alleviate the pain and anxiety associated with this technique. We advocate using high pressure intervention for emergency, due to swiftest method and feasible in case of lacking resources, such as sphygmomanometers in the ambulance. Interventions can be extrapolated to healthy young adults, adults and patients who have healthy vein status perception. Pressure intervention could be an alternative to heat intervention when performing vein cannulation due to its lower risk of transient paresthesia for older people who often suffer from arterial hypertension.