Methods: APPLAUD was a double-blind, placebo-controlled study in adults with CF, randomized (1:1) to LAU-7b or placebo for six consecutive treatment cycles of 21 days separated by 7-day drug-free periods.Eligible subjects had a percentage predicted forced expiratory volume in 1 second (FEV 1 pp) between 40% and 100% at screening and had had at least one pulmonary exacerbation (PEx) in the prior year.The study drug was administered orally once daily, in addition to standard of care.The primary efficacy endpoint was absolute change from baseline in FEV 1 pp at 24 weeks.Secondary endpoints included parameters related to PEx, quality of life, and systemic inflammatory and lipidomic biomarkers.Results: One hundred sixty-six subjects from 40 sites in the United States, Canada, and Australia were randomized.Preliminary results showed that absolute change in FEV 1 pp at 24 weeks was 0.8 points in favor of LAU-7b (-0.8 FEV 1 pp change from baseline in the LAU-7b arm, n = 83, versus -1.6 FEV 1 pp in the placebo arm, n = 83; p = 0.43).Planned stratification factor analysis showed that subjects with FEV 1 pp of 70% or greater at baseline responded better, resulting in a treatment difference of 3.0 points in FEV 1 pp at 24 weeks favoring LAU-7b (-0.9 FEV 1 pp change from baseline in the LAU-7b arm, n = 29, versus -3.9 FEV 1 pp in the placebo arm, n = 27; p = 0.06).Although the number of subjects was small, similar positive trends were noted in subjects already treated with CFTR modulators, including elexacaftor/tezacaftor/ivacaftor.PEx incidence and number of days of intravenous antibiotics were lower in the LAU-7b than the placebo arm.The safety profile of LAU-7b treatment was consistent with the safety profile observed in previous clinical studies with fenretinide.Serious adverse events and their severity and relationship distribution were similar between the two treatment arms, with no unexpected serious adverse reaction or deaths reported.Conclusions: Compared to placebo, LAU-7b treatment reduced loss of lung function by 50% at 24 weeks in the overall subject population and by 77% in the subgroup of subjects with mild lung disease (FEV 1 pp≥70%), suggesting a potential beneficial effect on the loss of lung function over 24 weeks.LAU-7b was well tolerated and had a favorable safety profile, similar to previously obtained data.The final efficacy data, including inflammation biomarker analyses, will be presented at the North American Cystic Fibrosis Conference.

A lumen /A (all p < 0.001), but not in A wt /A ( p = 0.35).Between 64% and 66% of AA pairs were defined as bronchiectasis and 59% as AWT.Conclusions: Progressive bronchiectasis can be observed in CwCF during late childhood into adolescence.AA analysis results agree with PRAGMA-CF results to monitor disease progression in CwCF.

were asked to fill out the Acceptability and Usability Questionnaire, which consisted of six questions ranked on a 4-point Likert scale.Results: Cohort 1 included 21 children aged 3 to 18 (mean age 9.25 ± 4.85), and Cohort 2 included 12 children aged 7 to 18 (mean age 12.15 ± 4.42).On 31 (94%) questionnaires returned, 35.5% of participants strongly agreed and 61.3% agreed with the statement "I [or my child] like(s) wearing the cough sensor."Similarly, most participants found the cough sensor easy to use (74.2% strongly agreed, 25.8% agreed) and comfortable to wear (64.5% strongly agreed, 29.0% agreed), although they found the adhesive sticker difficult to take off and the device too obvious or large.Conclusions: Although qualitative and quantitative acceptability and usability data were overall positive, we have redesigned the cough sensor for comfort and are continuing enrollment.The new sensor, 3.5 × 1.6 × 0.8 cm, is smaller and sits lower on the neck so participants can better conceal it underneath clothing (Figure 1).We are providing universal adhesive remover wipes to all participants.Future work includes long-term monitoring (1-2 weeks) of pulmonary exacerbations using the new devices and further assessing usability and acceptability from participants.

Methods: APPLAUD was a double-blind, placebo-controlled study in adults with CF, randomized (1:1) to LAU-7b or placebo for six consecutive treatment cycles of 21 days separated by 7-day drug-free periods.Eligible subjects had a percentage predicted forced expiratory volume in 1 second (FEV 1 pp) between 40% and 100% at screening and had had at least one pulmonary exacerbation (PEx) in the prior year.The study drug was administered orally once daily, in addition to standard of care.The primary efficacy endpoint was absolute change from baseline in FEV 1 pp at 24 weeks.Secondary endpoints included parameters related to PEx, quality of life, and systemic inflammatory and lipidomic biomarkers.Results: One hundred sixty-six subjects from 40 sites in the United States, Canada, and Australia were randomized.Preliminary results showed that absolute change in FEV 1 pp at 24 weeks was 0.8 points in favor of LAU-7b (-0.8 FEV 1 pp change from baseline in the LAU-7b arm, n = 83, versus -1.6 FEV 1 pp in the placebo arm, n = 83; p = 0.43).Planned stratification factor analysis showed that subjects with FEV 1 pp of 70% or greater at baseline responded better, resulting in a treatment difference of 3.0 points in FEV 1 pp at 24 weeks favoring LAU-7b (-0.9 FEV 1 pp change from baseline in the LAU-7b arm, n = 29, versus -3.9 FEV 1 pp in the placebo arm, n = 27; p = 0.06).Although the number of subjects was small, similar positive trends were noted in subjects already treated with CFTR modulators, including elexacaftor/tezacaftor/ivacaftor.PEx incidence and number of days of intravenous antibiotics were lower in the LAU-7b than the placebo arm.The safety profile of LAU-7b treatment was consistent with the safety profile observed in previous clinical studies with fenretinide.Serious adverse events and their severity and relationship distribution were similar between the two treatment arms, with no unexpected serious adverse reaction or deaths reported.Conclusions: Compared to placebo, LAU-7b treatment reduced loss of lung function by 50% at 24 weeks in the overall subject population and by 77% in the subgroup of subjects with mild lung disease (FEV 1 pp≥70%), suggesting a potential beneficial effect on the loss of lung function over 24 weeks.LAU-7b was well tolerated and had a favorable safety profile, similar to previously obtained data.The final efficacy data, including inflammation biomarker analyses, will be presented at the North American Cystic Fibrosis Conference.