Safety and efficacy of inhaled IBIO123 for mild-to-moderate COVID-19: a randomised, double-blind, dose-ascending, placebo-controlled, phase 1/2 trial.

BACKGROUND: COVID-19 severity is associated with its respiratory manifestations. Neutralising antibodies against SARS-CoV-2 administered systemically have shown clinical efficacy. However, immediate and direct delivery of neutralising antibodies via inhalation might provide additional respiratory clinical benefits. IBIO123 is a cocktail of three, fully human, neutralising monoclonal antibodies against SARS-CoV-2. We aimed to assess the safety and efficacy of inhaled IBIO123 in individuals with mild-to-moderate COVID-19. METHODS: This double-blind, dose-ascending, placebo-controlled, first-in-human, phase 1/2 trial recruited symptomatic and non-hospitalised participants with COVID-19 in South Africa and Brazil across 11 centres. Eligible participants were adult outpatients (aged ≥18 years; men and non-pregnant women) infected with COVID-19 (first PCR-confirmed within 72 h) and with mild-to-moderate symptoms, the onset of which had to be within 10 days of randomisation. Using permuted blocks of four, stratified by site, we randomly assigned participants (1:3) to receive single-dose placebo or IBIO123 (1 mg, 5 mg, or 10 mg) in phase 1, and single-dose placebo or IBIO123 (10 mg) in phase 2, in addition to local standard of care. Participants underwent serological testing to identify antibodies against SARS-CoV-2. Participants, investigators, and the study team were masked to treatment assignment. In phase 1, the primary outcome was the safety assessment in the safety population (ie, all participants who received an intervention). In phase 2, the primary outcome was the mean absolute change from baseline to day 5 in SARS-CoV-2 viral load measured by nasopharyngeal swabs analysed using a mixed model for repeated measures in the full analysis set (FAS; ie, participants with one analysable viral load value at baseline and at least one analysable viral load value at day 3 or day 5). Secondary clinical outcomes included safety from baseline to day 29, assessed by evaluating adverse events; the effect of IBIO123 on baseline COVID-19 symptoms resolution until day 6, with symptoms systemically evaluated by the investigators; and disease progression as measured by the COVID-19 WHO Clinical Progression Scale. For clinical endpoints in phase 2, we used a modified FAS (ie, participants who had at least one analysable viral load value over the course of the study, confirming that they were infected with SARS-CoV-2). This trial is now completed and is registered with ClinicalTrials.gov, NCT05298813. FINDINGS: Between Dec 4, 2021, and May 23, 2022, 24 participants were enrolled in phase 1. Between July 20, 2022, and Jan 4, 2023, 138 participants were enrolled in phase 2 and five were excluded because they did not meet the inclusion criteria. Participants were randomly assigned to receive IBIO123 (n=18) or placebo (n=6) in phase 1, and randomly assigned to receive IBIO123 (n=104) or placebo (n=34) in phase 2. In phase 2, the study was stopped before reaching the planned accrual because of a decline in COVID-19 incidence. In phase 1, no safety issues were observed. In phase 2, the difference in mean absolute change from baseline viral load to day 5 between participants in the IBIO123 group and participants in the placebo group was -0·29 log10 copies per mL (95% CI -1·32 to 0·75; p=0·45) in the FAS population and -0·49 log10 copies per mL (-1·56 to 0·58; p=0·20) in seropositive participants. In the modified FAS, 81 (69%) of 118 participants were at high risk of severe disease progression. The number of participants with resolution of respiratory symptoms at day 6 was 34 (42%) of 81 in the IBIO123 group versus five (17%) of 29 in the placebo group (p=0·017) in the modified FAS population and 19 (35%) of 55 versus three (14%) of 21 among participants at high risk (p=0·083). One participant died and one participant was hospitalised in the placebo group, whereas no deaths or hospitalisations were reported in the IBIO123 group. 39 (38%) of 104 participants in the IBIO123 group had adverse events, compared with 13 (38%) of 34 in the placebo group. INTERPRETATION: Inhalation of IBIO123 was safe. Despite the lack of significant reduction of viral load at day 5, treatment with IBIO123 resulted in a higher proportion of participants with complete resolution of respiratory symptoms at day 6. This study supports further clinical research on inhaled monoclonal antibodies in COVID-19 and respiratory diseases in general. FUNDING: Canadian Strategic Innovation Fund and Immune Biosolutions.

Assessing Reflective Parenting in Interaction With School-Aged Children.

The aim of this study was to examine whether it was possible to develop a reliable and valid assessment of reflective parenting implicit in interaction with school-aged children using an adaptation of the Squiggle paradigm developed by Winnicott ( 1968 ) and a manualized coding system (Normandin, Leroux, Ensink, Terradas, & Fonagy, 2015 ). A total of 158 mother-child dyads participated when children were age 5 to 12. Of this group, 89 children had experienced sexual abuse. Interrater reliability using the manualized coding system was excellent. The factor analysis identified a reflective parenting stance factor, in addition to an affectionate support factor and a negative parenting factor. Furthermore, there was a medium strength relationship between the mother's reflective parenting stance evident in her interactions with her child and parental reflective functioning assessed using the Parent Development Interview (Slade, Aber, Bresgi, Berger, & Kaplan, 2004 ), suggesting the parental reflective stance is a good indicator of parental reflective functioning in interaction. With regard to parent reports of child internalizing and externalizing behaviors, the reflective parenting stance was the only predictor of internalizing difficulties and a significant predictor of externalizing difficulties in addition to sexual abuse.

What is learned during the first moments of work?

The supervision of internships is often based on common sense. However, learning processes at workplace and their conditions remain partly unknown: what is really learned and under what conditions? Two studies on the learning of social working have been conducted, based on work analysis theories and methods. 6 experienced social workers and 4 interns in their first year of training have been interviewed according to the method of "explicitation" interview. The results show that professional learning can occur anyplace, anytime, under certain conditions and under certain forms that have been analyzed. These studies try to analyze the first internship as an entrance into a culture, through a psychological perspective.

Cross-national replication of the gender identity interview for children.

We administered the Gender Identity Interview for Children, a 12-item child-informant measure, to children referred clinically for gender identity problems in Toronto, Ontario, Canada (N = 329) and Amsterdam, The Netherlands (N = 228) and 173 control children. Confirmatory factor analysis identified a Cognitive Gender Confusion factor (4 items) and an Affective Gender Confusion factor (8 items). Patients from both clinics had a significantly higher deviant total score than the controls, and the Dutch patients had a significantly higher deviant score than the Toronto patients. In this cross-national study, we are the first to report on the validity of this measure to discriminate children with gender identity disorder from controls outside of North America.