A Study to Assess Vamorolone in Becker Muscular Dystrophy (BMD)

NCT05166109 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: VBP15-BMD-0011R01FD007284-01
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 2

Brief Summary

This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, and exploratory clinical efficacy of vamorolone 500mg (250mg for body weight \<50 kg) daily administered orally compared to placebo over a treatment period of 24 weeks in males with BMD. Funding Source - FDA OOPD

Conditions

Becker Muscular Dystrophy

Keywords

Becker Muscular Dystrophy; Duchenne Muscular Dystrophy; Duchenne and Becker Muscular Dystrophy; Muscular Dystrophy

Outcome Measures

Primary Outcomes (11)

• Safety as measured by Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) by system organ class (SOC and PT)

  Clinical AEs and clinical laboratory AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, dated June 14, 2010. Dose-limiting toxicities will be defined as follows: 1. The presence of a CTCAE Grade ≥ 3 AE, considered to be probably or definitely related to study drug 2. The presence of a CTCAE Grade ≥ 3 clinical laboratory AE considered to be probably or definitely related to study drug 3. Deterioration of the muscle condition, unexpected for the natural course of BMD and without other clear cause

  24 weeks

• Safety as measured by Sitting Blood Pressure

  Change in Sitting Blood Pressure from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Day 1, Week 4, Week 12, Week 24, Week 28

• Safety as measured by Heart Rate

  Change in Heart Rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Day 1, Week 4, Week 12, Week 24, Week 28

• Safety as measured by Respiratory Rate

  Change in Respiratory Rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Day 1, Week 4, Week 12, Week 24, Week 28

• Safety as measured by Body Temperature

  Change in Body Temperature from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Day 1, Week 4, Week 12, Week 24, Week 28

• Safety as measured by Body Weight

  Change in Body Weight from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Week 12, Week 24, Week 28

• Safety as measured by Height

  Change in Height from screening to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  Week 12, Week 24, Week 28

• Safety: concentration of blood laboratory biomarkers as assessed by standardized clinical laboratory reference ranges

  Blood biomarkers are White Blood cells (WBCs), Red Blood Cells, (RBCs), hemoglobin, Platelets, Sodium, Potassium, Chloride, Calcium, Blood Urea Nitrogen (BUN), Creatinine, Total Protein, Albumin, Total Bilirubin, Glucose, Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Glutamate Dehydrogenase (GLDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Creatine kinase (CK), Bicarbonate, Triglycerides, Total cholesterol, Low Density Lipoprotein (LDL) and High density Lipoprotein (HDL). Change from baseline to each of the scheduled on treatment and post-treatment time points will be assessed.

  Week 4, Week 12, Week 24

• Safety: concentration of urine laboratory biomarkers as measured by dipstick and microscopic analysis

  Urine biomarkers are protein, glucose, ketones, leukocyte esterase, White Blood Cells (WBCs), Red Blood Cells, (RBCs) and bacteria. Change from baseline to each of the scheduled on treatment and post-treatment time points will be assessed.

  Week 4, Week 12, Week 24

• Safety as measured by 12-lead ECG

  12-lead ECG as recorded after subject has rested quietly in a supine position for at least 5 minutes. ECG components are QRS duration, PR interval, QT interval and QTc interval. Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points.

  Week 12, Week 24

• Tolerability as measured by incidence of Premature Discontinuation

  Premature Discontinuation of study treatment due to adverse event.

  24 weeks

Secondary Outcomes (7)

• Pharmacokinetics as measured by AUCinf

  Day 1

• Safety as measured by serum concentration of osteocalcin

  Week 24

• Safety as measured by serum concentration of hemoglobin A1c (HbA1c)

  Week 24

• Safety as measured by fasting serum concentration of glucose

  Week 12, Week 24

• Safety as measured by fasting serum concentration of insulin

  Week 12, Week 24

Other Outcomes (3)

• Efficacy as measured by Time to Run/Walk Test (TTRW)

  Week 12, Week 24

• Efficacy as measured by North Star Ambulatory Assessment (NSAA) score

  Week 12, Week 24

• Tolerability as measured by NeuroQOL score

  24 weeks

Study Arms (2)

Vamorolone 500mg/day [250mg if <50kg body weight]

EXPERIMENTAL

Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).

Drug: Vamorolone

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).

Drug: Placebo

Interventions

Vamorolone DRUG

Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.

Also known as: VBP15

Vamorolone 500mg/day [250mg if <50kg body weight]

Placebo DRUG

Placebo to Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.

Also known as: Placebo to vamorolone

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject or Subject's parent(s) or legal guardian (s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures;
• Subject is a male and has a confirmed diagnosis of Becker dystrophy as defined as:
• Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'in-frame', and clinical picture consistent with Becker dystrophy, OR
• Complete dystrophin gene sequencing showing an alteration (small mutation, duplication, other) that is expected to allow production of an internally deleted dystrophin protein, with a typical clinical picture of Becker dystrophy;
• Subject is ≥ 18 years of age and \<65 years of age at time of informed consent;
• Subject is able to perform the timed run/walk 10 meters assessment (TTRW) in ≤ 30 sec at screening; assistive devices, cane or walker, are allowed.
• Subject has an NSAA score ≤ 32 at screening.
• Subject has not received oral glucocorticoids or other oral immunosuppressive agents for at least 3 months prior to first administration of study medication. \[Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first administration of study medication or if administered at stable dose beginning at least 4 weeks prior to first administration of study medication and anticipated to be used at the stable dose regimen for the duration of the study\];
• Subject has evidence of chicken pox immunity as determined by:
• Presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory from blood collected during the Screening Period; OR
• Documentation, provided at the Screening Visit, that the subject has received 2 doses of varicella vaccine, with or without serologic evidence of immunity, with the second of the 2 immunizations given at least 14 days prior to first administration of study medication;
• Subject is willing and able to comply with scheduled visits, study medication administration plan, and study procedures.
• Subject agrees to use barrier contraception methods during his participation in this study and for 30 days after the tapering dose is completed.

You may not qualify if:

• Subject has current or history of major renal or hepatic impairment, uncontrolled diabetes mellitus (defined as a diagnosis of diabetes with random glucose more than 1.5x ULN at screening and the patient has symptoms of polyuria or polydipsia) or immunosuppression;
• Subject has current or history of chronic systemic fungal or viral infections;
• Subject has had an acute illness within 4 weeks prior to the first dose of study medication
• Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), or mexrenone (mexrenoate potassium) within 4 weeks prior to administration of study medication;
• Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
• Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
• Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
• Subject is taking (or has taken within 4 weeks prior to first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
• Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
• Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to first dose of study medication; or
• Subject has previously been enrolled in the VBP15-BMD-001 study or any other vamorolone study.

Sponsors & Collaborators

• ReveraGen BioPharma, Inc.: lead
• Santhera Pharmaceuticals: collaborator

Study Sites (2)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Azienda Ospedale Universita Padova

Padua, 35129, Italy

Location

Related Publications (23)

• 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.

  PMID: 31451516 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.

  PMID: 32956407 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.

  PMID: 30745312 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.

  PMID: 30742306 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.

  PMID: 31446438 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.

  PMID: 30120816 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.

  PMID: 32434278 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.

  PMID: 29524454 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.

  PMID: 29666400 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.

  PMID: 28030841 BACKGROUND

• Liu X, Wang Y, Gutierrez JS, Damsker JM, Nagaraju K, Hoffman EP, Ortlund EA. Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment. Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24285-24293. doi: 10.1073/pnas.2006890117. Epub 2020 Sep 11.

  PMID: 32917814 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.

  PMID: 30219580 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.

  PMID: 29883261 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.

  PMID: 30166241 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.

  PMID: 32592467 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.

  PMID: 33617542 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.

  PMID: 25313409 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.

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• 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.

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• 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.

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• 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.

  PMID: 25392236 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.

  PMID: 27133900 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.

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MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Dystrophies

Interventions

VBP15 compound

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Paula Clemens, M.D.

  University of Pittsburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 21, 2021
• Study Start: July 7, 2022
• Primary Completion: August 18, 2025
• Study Completion: August 18, 2025
• Last Updated: September 18, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (1)