EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes substantial morbidity and mortality among infants, older adults, and immunocompromised adults. EDP-938, a nonfusion replication inhibitor of RSV, acts by modulating the viral nucleoprotein. METHODS: In a two-part, phase 2a, randomized, double-blind, placebo-controlled challenge trial, we assigned participants who had been inoculated with RSV-A Memphis 37b to receive EDP-938 or placebo. Different doses of EDP-938 were assessed. Nasal-wash samples were obtained from day 2 until day 12 for assessments. Clinical symptoms were assessed by the participants, and pharmacokinetic profiles were obtained. The primary end point was the area under the curve (AUC) for the RSV viral load, as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay. The key secondary end point was the AUC for the total symptom score. RESULTS: In part 1 of the trial, 115 participants were assigned to receive EDP-938 (600 mg once daily [600-mg once-daily group] or 300 mg twice daily after a 500-mg loading dose [300-mg twice-daily group]) or placebo. In part 2, a total of 63 participants were assigned to receive EDP-938 (300 mg once daily after a 600-mg loading dose [300-mg once-daily group] or 200 mg twice daily after a 400-mg loading dose [200-mg twice-daily group]) or placebo. In part 1, the AUC for the mean viral load (hours × log10 copies per milliliter) was 204.0 in the 600-mg once-daily group, 217.7 in the 300-mg twice-daily group, and 790.2 in the placebo group. The AUC for the mean total symptom score (hours × score, with higher values indicating greater severity) was 124.5 in the 600-mg once-daily group, 181.8 in the 300-mg twice-daily group, and 478.8 in the placebo group. The results in part 2 followed a pattern similar to that in part 1: the AUC for the mean viral load was 173.9 in the 300-mg once-daily group, 196.2 in the 200-mg twice-daily group, and 879.0 in the placebo group, and the AUC for the mean total symptom score was 99.3, 89.6, and 432.2, respectively. In both parts, mucus production was more than 70% lower in each EDP-938 group than in the placebo group. The four EDP-938 regimens had a safety profile similar to that of placebo. Across all dosing regimens, the EDP-938 median time to maximum concentration ranged from 4 to 5 hours, and the geometric mean half-life ranged from 13.7 to 14.5 hours. CONCLUSIONS: All EDP-938 regimens were superior to placebo with regard to lowering of the viral load, total symptom scores, and mucus weight without apparent safety concerns. (ClinicalTrials.gov number, NCT03691623.).

Feasibility of Parent-to-Parent Support in Recently Diagnosed Childhood Diabetes: The PLUS Study.

PURPOSE: The purpose of this study was to develop and test the feasibility of a parent-to-parent support intervention for parents whose child has recently been diagnosed with type 1 diabetes in the United Kingdom. METHODS: The research team conducted a formative evaluation, working with parents to design an individual-level parent-to-parent support intervention. Issues of recruitment, uptake, attrition, pattern of contact, and intervention acceptability were assessed. RESULTS: A US program was adapted in collaboration with a parents' advisory group. Of 19 parents nominated as potential mentors by their pediatric diabetes specialist nurses, 12 (63%) volunteered and 11 continued for the 12-month intervention period. Thirty-three children were diagnosed with diabetes in the study period, with 25 families eligible to participate as recipients of the intervention; 9 parents from 7 of those families participated, representing 28% of those eligible. Feedback from parents and clinic staff identified peer support as a welcome service. Lessons were learned about the nature of the supporting relationship (eg, proximity, connectedness, and managing endings) that will enhance the design of future peer support programs. CONCLUSIONS: Parent-to-parent support in the context of newly diagnosed childhood diabetes in the United Kingdom is feasible to deliver, with good engagement of mentors and clinic staff. The program was acceptable to parents who chose to participate, although uptake by parents whose child had been recently diagnosed was lower than expected. The results merit further investigation, including exploration of parent preference in relation to peer support.