A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03439670

Recruitment Status : Active, not recruiting

First Posted : February 20, 2018

Last Update Posted : September 17, 2020

Sponsor:

Collaborators:

European Union

Cooperative International Neuromuscular Research Group

Newcastle University

University of Pittsburgh

Information provided by (Responsible Party):

ReveraGen BioPharma, Inc.

No Study Results Posted on ClinicalTrials.gov for this Study

About Study Results Reporting on ClinicalTrials.gov

Recruitment Status :	Active, not recruiting
Estimated Primary Completion Date :	February 24, 2021
Estimated Study Completion Date :	August 1, 2021

Publications:

Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 2014 Jun;24(6):482-91. doi: 10.1016/j.nmd.2014.03.008. Epub 2014 Mar 22. Review.

Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919-28.

Evans NP, Misyak SA, Robertson JL, Bassaganya-Riera J, Grange RW. Immune-mediated mechanisms potentially regulate the disease time-course of duchenne muscular dystrophy and provide targets for therapeutic intervention. PM R. 2009 Aug;1(8):755-68. doi: 10.1016/j.pmrj.2009.04.010. Review.

Kumar A, Boriek AM. Mechanical stress activates the nuclear factor-kappaB pathway in skeletal muscle fibers: a possible role in Duchenne muscular dystrophy. FASEB J. 2003 Mar;17(3):386-96.

Acharyya S, Villalta SA, Bakkar N, Bupha-Intr T, Janssen PM, Carathers M, Li ZW, Beg AA, Ghosh S, Sahenk Z, Weinstein M, Gardner KL, Rafael-Fortney JA, Karin M, Tidball JG, Baldwin AS, Guttridge DC. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest. 2007 Apr;117(4):889-901. Epub 2007 Mar 22.

Dogra C, Changotra H, Wergedal JE, Kumar A. Regulation of phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor-kappa B signaling pathways in dystrophin-deficient skeletal muscle in response to mechanical stretch. J Cell Physiol. 2006 Sep;208(3):575-85.

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Spencer MJ, Tidball JG. Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscul Disord. 2001 Sep;11(6-7):556-64. Review.

Malik V, Rodino-Klapac LR, Mendell JR. Emerging drugs for Duchenne muscular dystrophy. Expert Opin Emerg Drugs. 2012 Jun;17(2):261-77. doi: 10.1517/14728214.2012.691965. Review.

Reeves EKM, Hoffman EP, Nagaraju K, Damsker JM, McCall JM. VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid. Bioorg Med Chem. 2013 Apr 15;21(8):2241-2249. doi: 10.1016/j.bmc.2013.02.009. Epub 2013 Feb 18. Erratum in: Bioorg Med Chem. 2015 Apr 1;23(7):1664.

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93. doi: 10.1016/S1474-4422(09)70271-6. Epub 2009 Nov 27. Review.

Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S, D'Amico A, Carlesi A, Vita G, Fanelli L, Berardinelli A, Torrente Y, Lanzillotta V, Viggiano E, D Ambrosio P, Cavallaro F, Frosini S, Barp A, Bonfiglio S, Scalise R, De Sanctis R, Rolle E, Graziano A, Magri F, Palermo C, Rossi F, Donati MA, Sacchini M, Arnoldi MT, Baranello G, Mongini T, Pini A, Battini R, Pegoraro E, Previtali S, Bruno C, Politano L, Comi GP, Bertini E, Mercuri E. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS One. 2014 Oct 1;9(10):e108205. doi: 10.1371/journal.pone.0108205. eCollection 2014. Erratum in: PLoS One. 2015;10(3):e0121882. PLoS One. 2015;10(12):e0144079.

Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003725. doi: 10.1002/14651858.CD003725.pub3. Review. Update in: Cochrane Database Syst Rev. 2016;(5):CD003725.

Heier CR, Damsker JM, Yu Q, Dillingham BC, Huynh T, Van der Meulen JH, Sali A, Miller BK, Phadke A, Scheffer L, Quinn J, Tatem K, Jordan S, Dadgar S, Rodriguez OC, Albanese C, Calhoun M, Gordish-Dressman H, Jaiswal JK, Connor EM, McCall JM, Hoffman EP, Reeves EK, Nagaraju K. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med. 2013 Oct;5(10):1569-85. doi: 10.1002/emmm.201302621. Epub 2013 Sep 9.

Damsker JM, Dillingham BC, Rose MC, Balsley MA, Heier CR, Watson AM, Stemmy EJ, Jurjus RA, Huynh T, Tatem K, Uaesoontrachoon K, Berry DM, Benton AS, Freishtat RJ, Hoffman EP, McCall JM, Gordish-Dressman H, Constant SL, Reeves EK, Nagaraju K. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice. PLoS One. 2013 May 7;8(5):e63871. doi: 10.1371/journal.pone.0063871. Print 2013.

Dillingham BC, Knoblach SM, Many GM, Harmon BT, Mullen AM, Heier CR, Bello L, McCall JM, Hoffman EP, Connor EM, Nagaraju K, Reeves EKM, Damsker JM. VBP15, a novel anti-inflammatory, is effective at reducing the severity of murine experimental autoimmune encephalomyelitis. Cell Mol Neurobiol. 2015 Apr;35(3):377-387. doi: 10.1007/s10571-014-0133-y. Epub 2014 Nov 13.

Dadgar S, Wang Z, Johnston H, Kesari A, Nagaraju K, Chen YW, Hill DA, Partridge TA, Giri M, Freishtat RJ, Nazarian J, Xuan J, Wang Y, Hoffman EP. Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. J Cell Biol. 2014 Oct 13;207(1):139-58. doi: 10.1083/jcb.201402079.

Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, Tran T, Smart S, McCarthy B, Taylor MD, Jefferies JL, Rafael-Fortney JA, Lowe J, Roble SL, Cripe LH. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):153-61. doi: 10.1016/S1474-4422(14)70318-7. Epub 2014 Dec 30. Erratum in: Lancet Neurol. 2015 Feb;14(2):135.

Avioli LV. Glucocorticoid effects on statural growth. Br J Rheumatol. 1993 May;32 Suppl 2:27-30.

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Sali A, Guerron AD, Gordish-Dressman H, Spurney CF, Iantorno M, Hoffman EP, Nagaraju K. Glucocorticoid-treated mice are an inappropriate positive control for long-term preclinical studies in the mdx mouse. PLoS One. 2012;7(4):e34204. doi: 10.1371/journal.pone.0034204. Epub 2012 Apr 3.

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Wehling-Henricks M, Oltmann M, Rinaldi C, Myung KH, Tidball JG. Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphofructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy. Hum Mol Genet. 2009 Sep 15;18(18):3439-51. doi: 10.1093/hmg/ddp288. Epub 2009 Jun 19.

Younes M, Neffati F, Touzi M, Hassen-Zrour S, Fendri Y, Béjia I, Ben Amor A, Bergaoui N, Najjar MF. Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients. Joint Bone Spine. 2007 Oct;74(5):472-6. Epub 2007 Jul 6.

Moon HJ, Choi KH, Lee SI, Lee OJ, Shin JW, Kim TW. Changes in blood glucose and cortisol levels after epidural or shoulder intra-articular glucocorticoid injections in diabetic or nondiabetic patients. Am J Phys Med Rehabil. 2014 May;93(5):372-8. doi: 10.1097/PHM.0000000000000001.

Investigator's Brochure, Version 4, Vamorolone (17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione) 4% Oral Suspension, ReveraGen BioPharma, Inc., January 10, 2017.

Fleishaker DL, Mukherjee A, Whaley FS, Daniel S, Zeiher BG. Safety and pharmacodynamic dose response of short-term prednisone in healthy adult subjects: a dose ranging, randomized, placebo-controlled, crossover study. BMC Musculoskelet Disord. 2016 Jul 16;17:293. doi: 10.1186/s12891-016-1135-3.

Hathout Y, Conklin LS, Seol H, Gordish-Dressman H, Brown KJ, Morgenroth LP, Nagaraju K, Heier CR, Damsker JM, van den Anker JN, Henricson E, Clemens PR, Mah JK, McDonald C, Hoffman EP. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children. Sci Rep. 2016 Aug 17;6:31727. doi: 10.1038/srep31727.

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FDA Draft Guidance for Industry: Duchenne muscular dystrophy and related dystrophinopathies: developing drugs for treatment. June 2015.

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Mazzone ES, Messina S, Vasco G, Main M, Eagle M, D'Amico A, Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Magri F, Corlatti A, Zucchini E, Brancalion B, Rossi F, Ferretti M, Motta MG, Cecio MR, Berardinelli A, Alfieri P, Mongini T, Pini A, Astrea G, Battini R, Comi G, Pegoraro E, Morandi L, Pane M, Angelini C, Bruno C, Villanova M, Vita G, Donati MA, Bertini E, Mercuri E. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscul Disord. 2009 Jul;19(7):458-61. doi: 10.1016/j.nmd.2009.06.368. Epub 2009 Jun 23.

McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, Reha A, Hirawat S, Miller LL. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve. 2010 Apr;41(4):500-10. doi: 10.1002/mus.21544.

Bello L, Kesari A, Gordish-Dressman H, Cnaan A, Morgenroth LP, Punetha J, Duong T, Henricson EK, Pegoraro E, McDonald CM, Hoffman EP; Cooperative International Neuromuscular Research Group Investigators. Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study. Ann Neurol. 2015 Apr;77(4):684-96. doi: 10.1002/ana.24370. Epub 2015 Mar 13.

Spurney C, Shimizu R, Morgenroth LP, Kolski H, Gordish-Dressman H, Clemens PR; CINRG Investigators. Cooperative International Neuromuscular Research Group Duchenne Natural History Study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy. Muscle Nerve. 2014 Aug;50(2):250-6. doi: 10.1002/mus.24163. Epub 2014 May 14.

McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman EP, Cnaan A; Cinrg Investigators. The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve. 2013 Jul;48(1):32-54. doi: 10.1002/mus.23807. Epub 2013 May 16.

Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, McDonald CM; CINRG Investigators. The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve. 2013 Jul;48(1):55-67. doi: 10.1002/mus.23808. Epub 2013 May 6.

Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13.

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