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

A Phase II Open-Label, Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD)

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Vamorolone

Detailed Description

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 of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a treatment period of 3 months in steroid-naïve boys ages 2 to <4, and glucocorticoid-treated and currently untreated boys ages 7 to <18 years with DMD.

The study is comprised of a 5-week Pretreatment Screening Period; a 1-day Pretreatment Baseline Period; a 3-month open-label Treatment Period (Weeks 1-12); and a 4-week open-label Dose-tapering Period (Weeks 13-16) for subjects who will not transition directly to further vamorolone or standard of care (SoC) glucocorticoid treatment at the end of the study.

Subjects will be enrolled into the study at the Screening Visit, at the time written informed consent is obtained.

Within the 2 to <4 years age group, the initial 10 eligible subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit. The subsequent 10 eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline Day -1 Visit.

Within the 7 to <18 years age group, both corticosteroid-treated and untreated, the initial 12 eligible subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit. The subsequent 12 eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline Day -1 Visit.

The first 6 subjects in each age group at 2 mg/kg will serve as the PK/safety run-in cohorts. PK assessments will be performed at week 2 and together with the safety assessment during the first 4 weeks of treatment this will be the basis to confirm whether 2 and 6 mg/kg/day will be used in the subsequent patients or if a dose adjustment is needed to avoid over or under-exposure in patients for any of the two age groups.

Glucocorticoid-treated subjects in the 7 to <18 years age group will take their final dose of SoC glucocorticoid therapy for DMD on Baseline Day -1, within 24 hours prior to administration of the first dose of vamorolone study medication.

All subjects in both age groups will begin their assigned vamorolone treatment on Treatment Period Day 1, and will continue to receive their assigned vamorolone treatment throughout the duration of the 3 month Treatment Period (Weeks 1-12).

At the end of the 3-month Treatment Period (Week 12), subjects will be given the option to receive vamorolone in an expanded access or compassionate use program, if possible, or to transition to SoC treatment for DMD (may include glucocorticoids). Subjects completing VBP15-006 and enrolling directly into the expanded access or compassionate use program or transitioning directly to SoC glucocorticoid treatment will not need to taper their vamorolone dose prior to participation in the expanded access or compassionate use program or initiation of SoC glucocorticoid treatment. All subjects who will not transition directly to further vamorolone or SoC glucocorticoid treatment will begin a 4 week open label Dose tapering Period during which the dose of study medication will be progressively reduced and discontinued.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Montréal, Canada, H4A 3J1
    • Recruiting
    • Montreal Childrens Hospital
    • Contact: Patricia Deeb; Phone Number: 24925 5149341934; Email: patricia.deeb@muhc.mcgill.ca
    • Principal Investigator: Maryam Oskoui, MD, M.Sc.
  • Alberta
    • Calgary, Alberta, Canada, AB T3B 6A8
      • Recruiting
      • Alberta's Children Hospital
      • Contact: Julie Dao; Email: julie.dao@ucalgary.ca
      • Principal Investigator: Jean Mah, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • British Columbia Children's Hospital
      • Contact: Nela Martic; Email: NMartic3@cw.bc.ca
      • Contact: Kathryn Selby, MBChB; Phone Number: 2161 604-875-2345; Email: kselby@cw.bc.ca
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Recruiting
      • Children's Hospital of Eastern Ontario
      • Contact: Laura Thompson; Email: LaThompson@cheo.on.ca
      • Principal Investigator: Hanns Lochmuller, MD
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • The Hospital for Sick Children
      • Contact: Ana Stosic; Email: ana.stosic@sickkids.ca
      • Principal Investigator: Hernan Gonorazky, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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; participants will be asked to give written or verbal assent according to local requirements;

2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD, defined as:

   1. Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
   2. Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame,' and clinical picture consistent with typical DMD, OR
   3. Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD;
3. Subject is male, 2 to <4 years or 7 to <18 years of age at time of enrollment in the study;
4. If 7 to <18 years of age and currently taking standard of care glucocorticoids for treatment of DMD, subject has been taking standard of care glucocorticoids at stable dose for at least 3 months prior to enrollment in the study, and will continue the same stable dose regimen through the date of the Baseline Day -1 Visit. [Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study];
5. If 7 to <18 years of age, and not currently glucocorticoid-treated, subject has not received oral glucocorticoids or other oral immunosuppressive agents for at least 3 months prior to enrollment. [Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study];
6. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. [Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from participating];

7. 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 had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to assignment to a dose group;
8. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

Exclusion Criteria:

1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
2. Subject has current or history of chronic systemic fungal or viral infections;
3. 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 enrollment;
4. Subject has a history of primary hyperaldosteronism;
5. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
6. If 2 to <4 years of age, subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last use at least 3 months prior to enrollment, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study];
7. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
8. Subject has used idebenone within 4 weeks prior to enrollment;
9. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
10. 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;
11. Subject is taking (or has taken within 4 weeks prior to enrollment) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
12. Subject is taking (or has taken within 3 months prior to enrollment) any medication indicated for DMD, including Exondys51, Exondys53, Exondys45, Viltepso and Translarna;
13. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
14. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to enrollment;
15. Subject has previously been enrolled in the VBP15-006 study or any other vamorolone study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1; Patients in Treatment Group 1 must be ages 2-<4 years and will receive Vamorolone at 2.0 mg/kg/day for the duration of the study. Treatment Group 1 will be enrolled prior to Treatment Group 2.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 2; Patients in Treatment Group 2 must be ages 2-<4 years and will receive Vamorolone at 6.0 mg/kg/day for the duration of the study. Treatment Group 2 will be enrolled after Treatment Group 1.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 3; Patients in Treatment Group 3 must be ages 7-<18 years and must be steroid untreated at entry. Treatment Group 3 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 4; Patients in Treatment Group 4 must be ages 7-<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 4 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 5; Patients in Treatment Group 5 must be ages 7-<18 years and must be steroid untreated at entry. Treatment Group 5 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 6; Patients in Treatment Group 6 must be ages 7-<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 6 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15
Experimental: Treatment Group 7; Patients in Treatment Group 7 must be ages 12-<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 7 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.	Drug: Vamorolone; Oral administration of vamorolone for 12 weeks.; Other Names: VBP15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index (BMI) from baseline to Week 12	Body Mass Index is a measure of weight adjusted for height.	12 weeks
Change in Body Mass Index (BMI) z-score from baseline to Week 12	Body Mass Index z-scores is a measure of relative weight adjusted for child age and sex.	12 weeks
Change in Weight from baseline to each of the scheduled on treatment and post-treatment assessment time points	Body weight will be assessed at each of the scheduled time points.	Week 2, Week 6, Week 12, Week 16
Change in Height from baseline to Week 12	Standing height will be assessed for subjects ages 2-<4 years; height calculated from ulnar length in subjects ages 7-<18.	Week 12
Change in Height z score from baseline to Week 12	Standing height will be assessed for subjects ages 2-<4 years; height calculated from ulnar length in subjects ages 7-<18.	Week 12
Change in sitting blood pressure from baseline to each of the scheduled on-treatment and post-treatment assessment time points	Sitting blood pressure will be assessed at scheduled on-treatment and post-treatment time points.	Day 1, Week 2, Week 6, Week 12, Week 16
Change in heart rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points	Heart rate will be assessed at scheduled on-treatment and post-treatment time points.	Day 1, Week 2, Week 6, Week 12, Week 16
Change in respiratory rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points	Respiratory rate will be assessed at scheduled on-treatment and post-treatment time points.	Day 1, Week 2, Week 6, Week 12, Week 16
Change in body temperature from baseline to each of the scheduled on-treatment and post-treatment assessment time points	Body temperature will be assessed at scheduled on-treatment and post-treatment time points.	Day 1, Week 2, Week 6, Week 12, Week 16
Number of participants with Cushingoid features	Cushingoid features measured by the presence of buffalo hump obesity, striations, adiposity, hypertension, diabetes, or osteoporosis. Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points.	Week 6, Week 12, Week 16
Number of participants with abnormal blood laboratory test results	Blood samples will be collected from subjects for the analysis of clinical chemistry parameters, including White Blood cells (WBCs), Red Blood Cells, (RBCs), hemoglobin, Platelets, Sodium, Potassium, Chloride, Calcium, Inorganic Phosphorus, Blood Urea Nitrogen (BUN), Creatinine, Total Protein, Albumin, Bicarbonate, Lactate Dehydrogenase (LDH), Cystatin C, Total Bilirubin, Uric Acid, Glucose, Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Creatine kinase (CK), Lipase, Amylase, Vitamin D, 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.	Day 1, Week 6, Week 12, Week 16
Number of participants with abnormal urine laboratory test results	Urine biomarkers will include protein, glucose, ketones, leukocyte esterase, White Blood Cells (WBCs), Red Blood Cells, (RBCs) and bacteria and will be assessed by dipstick and microscopic analysis. Change from baseline to each of the scheduled on treatment and post-treatment time points will be assessed.	Day 1, Week 6, Week 12, Week 16
Number of participants with abnormal ECGs	12-lead 1electrocardiogram (ECG) as recorded after subject has rested quietly in a supine position for at least 5 minutes. ECG components are QRS duration, PR [PQ] interval, RR interval, QT interval and QTc. Change from baseline to Week 12	Week 12
Number of participants with Glaucoma	Glaucoma as by measured by ocular pressure.Week 12 assessments compared to baseline.	12 weeks
Number of participants with Cataracts	Cataracts as measured by the presence of partial or complete opacity of the crystalline lens of one or both eyes. Week 12 assessments compared to baseline.	12 weeks
Number of Participants with Adverse Events as Assessed by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03)	An Adverse Event is any untoward medical occurrence in a subject and does not necessarily have to have a causal relationship with the intervention. Pre-existing conditions that worsen during the study are to be reported as AEs.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the Curve infinity (AUCinf) following oral administration	The pre-dose and post-dose plasma concentration measurements of vamorolone at Day 1 and Week 2 will be used for comparison of drug exposures by age group, dose level, and glucocorticoid treatment at entry (7 to <18 years only).	Day 1, Week 2
Change in morning cortisol concentration from baseline to Week 12	Adrenal suppression is directly associated with risk of adrenal crisis, delay of puberty and stunting of growth. Measurement of morning cortisol concentrations will reflect the degree of adrenal suppression. Cortisol measures falling below 3.6 µg/dL (or 100 nM) will be considered to be indicative of the development of adrenal suppression.	Week 12
Change in fasting serum concentration of glucose from baseline to Week 12	Glucocorticoids cause both acute and chronic insulin resistance, with serum elevations of both insulin and glucose. Measures of hyperinsulinemia and hyperglycemia are accepted measures of insulin resistance. Fasting glucose will be measured at baseline and Week 12.	Week 12
Change in fasting serum concentration of insulin from baseline to Week 12	Glucocorticoids cause both acute and chronic insulin resistance, with serum elevations of both insulin and glucose. Measures of hyperinsulinemia and hyperglycemia are accepted measures of insulin resistance. Fasting insulin will be measured at baseline and Week 12.	Week 12
Change in serum concentration of hemoglobin A1c (HbA1c) from baseline to Week 12	Glucocorticoids cause both acute and chronic insulin resistance, with serum elevations of both insulin and glucose. Measures of hyperinsulinemia and hyperglycemia are accepted measures of insulin resistance. Hemoglobin A1c (HbA1c) will be measured at baseline and Week 12.	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bayley Scales of Infant and Toddler Development-III (Bayley-III) Gross Motor scale (ages 2 to <4 years only) from baseline to Week 12	The Bayley-III Gross Motor scale is a functional assessment which was chosen as an accurate reflection of muscle strength for subjects with DMD ages 2 to <4 years. The minimum score value is 0 and the maximum score value is 72. Higher scores mean a better outcome.	Week 12
Change in Performance of Upper Limb (PUL) test (7 to <18 years only) from baseline to Week 12	The Performance of Upper Limb is a functional assessment which was chosen as an accurate reflection of muscle strength for subjects with DMD ages 7 to <18 years. The minimum score value is 0 and the maximum score value is 42. Higher scores mean a better outcome.	Week 12
Change in Personal Adjustment and Role Skills Scale, ed. 3 (PARS III) questionnaire from baseline to Week 12	The PARS III is a scale designed to assess behavior and measure psychosocial adjustment of children with chronic physical illnesses. The PARS III will be completed by the parent(s)/guardian(s) at the Screening and Week 12 Visits. The minimum score value is 28 and the maximum score value is 112. Higher scores mean better personal adjustment.	Week 12
Change in Pediatric Outcome Data Collection Instrument (PODCI) from baseline to Week 12	Physical functioning will be measured using the Pediatric Outcomes Data Collection Instrument (PODCI). The minimum score value is 0 and the maximum score value is 100. Higher scores mean a better outcome.	Week 12
Study Medication Acceptability Assessment (ages 7 to <18 years only) at each of the scheduled study assessment time points	Subjects in the 7 to <18 years age group will complete the Study Medication Acceptability Assessment. The minimum score value is 2 and the maximum score value is 10. Higher scores mean the medication is more acceptable.	Week 6, Week 12
Ease of Study Medication Administration Assessment (ages 2 to <4 years only) at each of the scheduled study assessment time points	The parent(s)/legal guardian(s) of each subject in the 2 to <4 years age group will be asked to complete the Ease of Study Medication Administration Assessment. The minimum score value is 2 and the maximum score value is 10. Higher scores mean the medication is easier to administer.	Week 6, Week 12
Change in concentration of serum osteocalcin from baseline to Week 12	Measures of serum osteocalcin are reflective of bone formation, and measures of serum C terminal peptide fragment of collagen 1 (CTX) are reflective of bone reabsorption. Ratios of osteocalcin and CTX predict later clinical safety concerns of osteopenia and bone fragility.	Week 12
Change in concentration of serum aminoterminal propeptide of type I collagen (P1NP) from baseline to Week 12	Measures of serum P1NP are reflective of bone formation.	Week 12
Change in serum concentration of C terminal peptide fragment of collagen 1 (CTX) from baseline to Week 12	Measures of serum osteocalcin are reflective of bone formation, and measures of serum CTX are reflective of bone reabsorption. Ratios of osteocalcin and CTX predict later clinical safety concerns of osteopenia and bone fragility.	Week 12

Collaborators and Investigators

• Sponsor: Santhera Pharmaceuticals
• Collaborators: Santhera Pharmaceuticals
• Investigators: Principal Investigator: Jean K Mah, M.D., Alberta Children's Hospital Research Institute, University of Calgary

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
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• 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.
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Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; Muscular Dystrophy; Becker Muscular Dystrophy; Duchenne and Becker Muscular Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: VBP15-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No