Guglieri, M., Clemens, P.R., Perlman, S.J., Smith, E.C., Horrocks, I., Finkel, R.S., Mah, J.K., Deconinck, N., Goemans, N., Haberlova, J., Straub, V., Mengle-Gaw, L.J., Schwartz, B.D., Harper, A.D., Shieh, P.B., Waele, L. De, Castro, D., Yang, M.L., Ryan, M.M., McDonald, C.M., Tulinius, M., Webster, R., McMillan, H.J., Kuntz, N.L., Rao, V.K., Baranello, G., Spinty, S., Childs, A.M., Sbrocchi, A.M., Selby, K.A., Monduy, M., Nevo, Y., Vilchez-Padilla, J.J., Nascimento-Osorio, A., Niks, E.H., Groot, I.J.M. de, Katsalouli, M., James, M.K., Anker, J. van den, Damsker, J.M., Ahmet, A., Ward, LM, Jaros, M., Shale, P., Dang, U.J., Hoffman, E.P., Guglieri, M., Clemens, P.R., Perlman, S.J., Smith, E.C., Horrocks, I., Finkel, R.S., Mah, J.K., Deconinck, N., Goemans, N., Haberlova, J., Straub, V., Mengle-Gaw, L.J., Schwartz, B.D., Harper, A.D., Shieh, P.B., Waele, L. De, Castro, D., Yang, M.L., Ryan, M.M., McDonald, C.M., Tulinius, M., Webster, R., McMillan, H.J., Kuntz, N.L., Rao, V.K., Baranello, G., Spinty, S., Childs, A.M., Sbrocchi, A.M., Selby, K.A., Monduy, M., Nevo, Y., Vilchez-Padilla, J.J., Nascimento-Osorio, A., Niks, E.H., Groot, I.J.M. de, Katsalouli, M., James, M.K., Anker, J. van den, Damsker, J.M., Ahmet, A., Ward, LM, Jaros, M., Shale, P., Dang, U.J., and Hoffman, E.P.
Item does not contain fulltext, IMPORTANCE: Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life. OBJECTIVE: To determine if vamorolone, a structurally unique dissociative steroidal anti-inflammatory drug, is able to retain efficacy while reducing safety concerns with use in Duchenne muscular dystrophy (DMD). DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo- and prednisone-controlled 24-week clinical trial, conducted from June 29, 2018, to February 24, 2021, with 24 weeks of follow-up. This was a multicenter study (33 referral centers in 11 countries) and included boys 4 to younger than 7 years of age with genetically confirmed DMD not previously treated with corticosteroids. INTERVENTIONS: The study included 4 groups: placebo; prednisone, 0.75 mg/kg per day; vamorolone, 2 mg/kg per day; and vamorolone, 6 mg/kg per day. MAIN OUTCOMES AND MEASURES: Study outcomes monitored (1) efficacy, which included motor outcomes (primary: time to stand from supine velocity in the vamorolone, 6 mg/kg per day, group vs placebo; secondary: time to stand from supine velocity [vamorolone, 2 mg/kg per day], 6-minute walk distance, time to run/walk 10 m [vamorolone, 2 and 6 mg/kg per day]; exploratory: NorthStar Ambulatory Assessment, time to climb 4 stairs) and (2) safety, which included growth, bone biomarkers, and a corticotropin (ACTH)-challenge test. RESULTS: Among the 133 boys with DMD enrolled in the study (mean [SD] age, 5.4 [0.9] years), 121 were randomly assigned to treatment groups, and 114 completed the 24-week treatment period. The trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m/s vs placebo -0.01 [0.01] m/s; 95% CI, 0.02-0.10; P = .002) and the first 4 sequential secondary end points: time to stand velocity, vamorolone, 2 mg/kg per day, vs placebo; 6-minute walk test, vamo