A Study to Assess Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD)

Summary

This Phase II study is an open-label, multiple dose study to evaluate the safety, tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical functioning vamorolone over a treatment period of 12 weeks in steroid-naïve boys ages 2 to \<4 years, and glucocorticoid-treated and currently untreated boys ages 7 to \<18 years with DMD.

Timeline

Start

2022-03-21

Primary completion

2024-07-16

Completion

2024-07-16

Publications

• Background 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; Cooperative International Neuromuscular Research Group. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology. 2019 Sep 24;93(13):e1312-e1323. doi: 10.1212/WNL.0000000000008168. Epub 2019 Aug 26.
• Background Smith EC, Conklin LS, Hoffman EP, Clemens PR, Mah JK, Finkel RS, Guglieri M, Tulinius M, Nevo Y, Ryan MM, Webster R, Castro D, Kuntz NL, Kerchner L, Morgenroth LP, Arrieta A, Shimony M, Jaros M, Shale P, Gordish-Dressman H, Hagerty L, Dang UJ, Damsker JM, Schwartz BD, Mengle-Gaw LJ, McDonald CM; CINRG VBP15 and DNHS Investigators. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study. PLoS Med. 2020 Sep 21;17(9):e1003222. doi: 10.1371/journal.pmed.1003222. eCollection 2020 Sep.
• Background Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. Print 2019 Feb.
• Background Mavroudis PD, van den Anker J, Conklin LS, Damsker JM, Hoffman EP, Nagaraju K, Clemens PR, Jusko WJ. Population Pharmacokinetics of Vamorolone (VBP15) in Healthy Men and Boys With Duchenne Muscular Dystrophy. J Clin Pharmacol. 2019 Jul;59(7):979-988. doi: 10.1002/jcph.1388. Epub 2019 Feb 11.
• Background Damsker JM, Cornish MR, Kanneboyina P, Kanneboyina I, Yu Q, Lipson R, Phadke A, Knoblach SM, Panchapakesan K, Morales M, Fiorillo AA, Partridge T, Nagaraju K. Vamorolone, a dissociative steroidal compound, reduces collagen antibody-induced joint damage and inflammation when administered after disease onset. Inflamm Res. 2019 Nov;68(11):969-980. doi: 10.1007/s00011-019-01279-z. Epub 2019 Aug 24.
• Background Akkad H, Cacciani N, Llano-Diez M, Corpeno Kalamgi R, Tchkonia T, Kirkland JL, Larsson L. Vamorolone treatment improves skeletal muscle outcome in a critical illness myopathy rat model. Acta Physiol (Oxf). 2019 Feb;225(2):e13172. doi: 10.1111/apha.13172. Epub 2018 Sep 6.
• Background Li X, Conklin LS, van den Anker J, Hoffman EP, Clemens PR, Jusko WJ. Exposure-Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy. J Clin Pharmacol. 2020 Oct;60(10):1385-1396. doi: 10.1002/jcph.1632. Epub 2020 May 20.
• Background Hoffman EP, Riddle V, Siegler MA, Dickerson D, Backonja M, Kramer WG, Nagaraju K, Gordish-Dressman H, Damsker JM, McCall JM. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes. Steroids. 2018 Jun;134:43-52. doi: 10.1016/j.steroids.2018.02.010. Epub 2018 Mar 8.
• Background Almeida LEF, Damsker JM, Albani S, Afsar N, Kamimura S, Pratt D, Kleiner DE, Quezado M, Gordish-Dressman H, Quezado ZMN. The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice. Sci Rep. 2018 Apr 17;8(1):6081. doi: 10.1038/s41598-018-24274-6.
• Background Wells E, Kambhampati M, Damsker JM, Gordish-Dressman H, Yadavilli S, Becher OJ, Gittens J, Stampar M, Packer RJ, Nazarian J. Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor. Oncotarget. 2017 Feb 7;8(6):9366-9374. doi: 10.18632/oncotarget.14070.
• Background Conklin LS, Damsker JM, Hoffman EP, Jusko WJ, Mavroudis PD, Schwartz BD, Mengle-Gaw LJ, Smith EC, Mah JK, Guglieri M, Nevo Y, Kuntz N, McDonald CM, Tulinius M, Ryan MM, Webster R, Castro D, Finkel RS, Smith AL, Morgenroth LP, Arrieta A, Shimony M, Jaros M, Shale P, McCall JM, Hathout Y, Nagaraju K, van den Anker J, Ward LM, Ahmet A, Cornish MR, Clemens PR. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol Res. 2018 Oct;136:140-150. doi: 10.1016/j.phrs.2018.09.007. Epub 2018 Sep 13.
• Background Fiorillo AA, Tully CB, Damsker JM, Nagaraju K, Hoffman EP, Heier CR. Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone. Physiol Genomics. 2018 Sep 1;50(9):735-745. doi: 10.1152/physiolgenomics.00134.2017. Epub 2018 Jun 8.
• Background Sreetama SC, Chandra G, Van der Meulen JH, Ahmad MM, Suzuki P, Bhuvanendran S, Nagaraju K, Hoffman EP, Jaiswal JK. Membrane Stabilization by Modified Steroid Offers a Potential Therapy for Muscular Dystrophy Due to Dysferlin Deficit. Mol Ther. 2018 Sep 5;26(9):2231-2242. doi: 10.1016/j.ymthe.2018.07.021. Epub 2018 Aug 27.
• Background Dang UJ, Ziemba M, Clemens PR, Hathout Y, Conklin LS; CINRG Vamorolone 002/003 Investigators; Hoffman EP. Serum biomarkers associated with baseline clinical severity in young steroid-naive Duchenne muscular dystrophy boys. Hum Mol Genet. 2020 Aug 29;29(15):2481-2495. doi: 10.1093/hmg/ddaa132.
• Background Ziemba M, Barkhouse M, Uaesoontrachoon K, Giri M, Hathout Y, Dang UJ, Gordish-Dressman H, Nagaraju K, Hoffman EP. Biomarker-focused multi-drug combination therapy and repurposing trial in mdx mice. PLoS One. 2021 Feb 22;16(2):e0246507. doi: 10.1371/journal.pone.0246507. eCollection 2021.
• Background 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.
• Background 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.
• Background 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.
• Background Freishtat RJ, Nino G, Tsegaye Y, Alcala SE, Benton AS, Watson AM, Reeves EK, Haider SK, Damsker JM. Pharmacologically-induced mitotic synchrony in airway epithelial cells as a mechanism of action of anti-inflammatory drugs. Respir Res. 2015 Oct 29;16:132. doi: 10.1186/s12931-015-0293-4.
• Background 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.
• Background Garvin LM, Chen Y, Damsker JM, Rose MC. A novel dissociative steroid VBP15 reduces MUC5AC gene expression in airway epithelial cells but lacks the GRE mediated transcriptional properties of dexamethasone. Pulm Pharmacol Ther. 2016 Jun;38:17-26. doi: 10.1016/j.pupt.2016.04.004. Epub 2016 Apr 29.
• Background Damsker JM, Conklin LS, Sadri S, Dillingham BC, Panchapakesan K, Heier CR, McCall JM, Sandler AD. VBP15, a novel dissociative steroid compound, reduces NFkappaB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis. Inflamm Res. 2016 Sep;65(9):737-43. doi: 10.1007/s00011-016-0956-8. Epub 2016 Jun 3.
• Mah JK, Gonorazky HD, Nigro E, Lochmuller H, Aleman A, Yaworski A, Oskoui M, Sbrocchi AM, Selby KA, de Vera A, Mathur R, Gresko E, Linden A, Dutreix C, Hoffman EP. Vamorolone Safety, Pharmacokinetics, and Exploratory Efficacy in Duchenne Muscular Dystrophy: A Phase II, Nonrandomized, Multiple-Dose Study in 2-<4-Year-Old Boys. Neurology. 2026 Jun 9;106(11):e218066. doi: 10.1212/WNL.0000000000218066. Epub 2026 May 15.
• Lochmuller H, Gonorazky H, Nigro E, Mah JK, Aleman A, Yaworski A, Oskoui M, Sbrocchi AM, Selby K, de Vera A, McAdam L, Gresko E, Linden A, Dutreix C, Hoffman EP. Results of a phase II open-label, multiple-dose study of vamorolone (VBP15-006) in 7- to < 18-year-old boys with duchenne muscular dystrophy. J Neurol. 2026 Mar 3;273(3):177. doi: 10.1007/s00415-026-13711-6.

Drugs

Indications