Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

BACKGROUND: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1. METHODS: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa. For each patient, a primary wound pair was selected, with the wounds matched according to size, region, and appearance. The wounds within each pair were randomly assigned in a 1:1 ratio to receive weekly application of either B-VEC or placebo for 26 weeks. The primary end point was complete wound healing of treated as compared with untreated wounds at 6 months. Secondary end points included complete wound healing at 3 months and the change from baseline to weeks 22, 24, and 26 in pain severity during changes in wound dressing, assessed with the use of a visual analogue scale (scores range from 0 to 10, with higher scores indicating greater pain). RESULTS: Primary wound pairs were exposed to B-VEC and placebo in 31 patients. At 6 months, complete wound healing occurred in 67% of the wounds exposed to B-VEC as compared with 22% of those exposed to placebo (difference, 46 percentage points; 95% confidence interval [CI], 24 to 68; P = 0.002). Complete wound healing at 3 months occurred in 71% of the wounds exposed to B-VEC as compared with 20% of those exposed to placebo (difference, 51 percentage points; 95% CI, 29 to 73; P<0.001). The mean change from baseline to week 22 in pain severity during wound-dressing changes was -0.88 with B-VEC and -0.71 with placebo (adjusted least-squares mean difference, -0.61; 95% CI, -1.10 to -0.13); similar mean changes were observed at weeks 24 and 26. Adverse events with B-VEC and placebo included pruritus and chills. CONCLUSIONS: Complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo. Pruritus and mild systemic side effects were observed in patients treated with B-VEC. Longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. (Funded by Krystal Biotech; GEM-3 ClinicalTrials.gov number, NCT04491604.).

Outcomes of Exercise Training Following the Use of a Birthing Ball During Pregnancy and Delivery.

Fournier, D, Feeney, G, and Mathieu, M-E. Outcomes of exercise training following the use of a birthing ball during pregnancy and delivery. J Strength Cond Res 31(7): 1941-1947, 2017- Using a birthing ball (BB) is an exercise form that is growing in popularity. Improved delivery outcomes have been recently reported with as little a 6-8 hours of training per week; however, little is known regarding lower and higher training levels. The aim of this study was to document whether more time spent training with a BB resulted in improved delivery outcomes for the mother and the newborn. This quasi-experimental study was conducted with a sample of women who participated in 1 to 28 supervised exercise classes during pregnancy according to the Ballon Forme program offered in nonclinical settings (http://ballonforme.com), with the option of completing the supervised BB exercises performed at home. Thirty women who gave birth naturally were included in the study. Mean BB training time was 22.3 hours (SD = 16.6 hours). A greater BB training time was significantly associated with shorter labor duration (r = -0.408; p = 0.031) and specific stages of labor (stage 1 [dilatation/active stage] [r = -0.372; p = 0.043] and stage 2 [expulsion] [r = -0.415; p = 0.028]). Increased participation in BB supervised classes was more closely associated with quicker deliveries than those of home based BB exercises. No associations between training time and adverse effects of labor parameters or the baby's health were noted. Greater involvement in BB training seems to lead to quicker deliveries than lower levels of involvement; it also has the benefit of supervised practice.