دورية أكاديمية
Data from: Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function
| العنوان: | Data from: Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function |
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| المؤلفون: | Hoffman, Eric P., Schwartz, Benjamin D., Mengle-Gaw, Laurel J., Smith, Edward C., Castro, Diana, Mah, Jean K., McDonald, Craig M., Kuntz, Nancy L., Finkel, Richard S., Guglieri, Michela, Bushby, Katharine, Tulinius, Mar, Nevo, Yoram, Ryan, Monique M., Webster, Richard, Smith, Andrea L., Morgenroth, Lauren P., Arrieta, Adrienne, Shimony, Maya, Siener, Catherine, Jaros, Mark, Shale, Phil, McCall, John M., Nagaraju, Kanneboyina, van den Anker, John, Conklin, Laurie S., Cnaan, Avital, Gordish-Dressman, Heather, Damsker, Jesse M., Clemens, Paula R. |
| سنة النشر: | 2019 |
| المجموعة: | Dryad Digital Repository (Duke University) |
| مصطلحات موضوعية: | Clinical trials Observational study (Cohort, Case control), Class IV, Muscle disease, Duchenne muscular dystrophy, vamorolone |
| جغرافية الموضوع: | United States, United Kingdom, Sweden, Israel, Australia |
| الوقت: | Canada |
| الوصف: | Objective: We carried out first-in-patient studies of vamorolone, a first-in-class dissociative steroidal anti-inflammatory drug, in Duchenne muscular dystrophy. Methods: An open-label, multiple-ascending dose study of vamorolone was conducted in 48 boys with Duchenne muscular dystrophy (4 to <7 years, steroid-naïve). Dose levels were 0.25, 0.75, 2.0 and 6.0 mg/kg/day using an oral suspension formulation (12 boys/dose level; 1/3rd to 10x glucocorticoid dose in DMD). Results: Over a 24-week treatment period, oral administration of vamorolone at all doses tested was safe and well-tolerated. The 2.0 mg/kg/day dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks vamorolone treatment versus natural history controls), without evidence of most adverse effects of glucocorticoids. Significant dose-responsive improvements in 10 meter run/walk, and six-minute walk test were observed for 2.0 and 6.0 mg/kg/day dose groups. The morbidity of most concern to many chronic glucocorticoid users, bone loss, was not seen with vamorolone at any dose, as evidenced by serum osteocalcin. Biomarker outcomes for adrenal suppression and insulin resistance were also less impacted in vamorolone-treated DMD patients, relative to published studies of glucocorticoid therapy. Conclusions: Vamorolone demonstrated both efficacy and a reduction in adverse effects in DMD patients compared to traditional glucocorticoids in a 24-week, open-label study. Vamorolone has potential to replace chronic glucocorticoids in many disorders where side effects detract from patient quality of life. Classification of Evidence: This study provides Class II evidence that certain dosages of vamorolone are well tolerated and effective in improving muscle function in DMD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Hoffman EP, Schwartz BD, Mengle-Gaw LJ, Smith EC, Castro D, Mah JK, McDonald CM, Kuntz NL, Finkel RS, Guglieri M, Bushby K, Tulinius M, Nevo Y, Ryan MM, Webster R, Smith AL, Morgenroth LP, Arrieta A, Shimony M, Siener C, Jaros M, Shale P, McCall JM, Nagaraju K, van den Anker J, Conklin LS, Cnaan A, Gordish-Dressman H, Damsker JM, Clemens PR (2019) Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology.; http://hdl.handle.net/10255/dryad.208749Test |
| DOI: | 10.5061/dryad.1rd4hc7 |
| الإتاحة: | https://doi.org/10.5061/dryad.1rd4hc7Test https://doi.org/10.5061/dryad.1rd4hc7/2Test https://doi.org/10.1212/WNL.0000000000008168Test http://hdl.handle.net/10255/dryad.208749Test |
| رقم الانضمام: | edsbas.D1A6F45D |
| قاعدة البيانات: | BASE |
| DOI: | 10.5061/dryad.1rd4hc7 |
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