Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Cooperative International Neuromuscular Research Group

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). METHODS: An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. RESULTS: Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy. CONCLUSIONS: Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

Original languageEnglish (US)
Pages (from-to)e1312-e1323
JournalNeurology
Volume93
Issue number13
DOIs
StatePublished - Sep 24 2019
Externally publishedYes

Fingerprint

Duchenne Muscular Dystrophy
Glucocorticoids
Muscles
Natural History
Biomarkers
Osteocalcin
Osteogenesis
Oral Administration
Insulin Resistance
Suspensions
Anti-Inflammatory Agents
Therapeutics
Steroids
Morbidity
Bone and Bones
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. / Cooperative International Neuromuscular Research Group.

In: Neurology, Vol. 93, No. 13, 24.09.2019, p. e1312-e1323.

Research output: Contribution to journalArticle

Cooperative International Neuromuscular Research Group 2019, 'Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function', Neurology, vol. 93, no. 13, pp. e1312-e1323. https://doi.org/10.1212/WNL.0000000000008168
Cooperative International Neuromuscular Research Group. / Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. In: Neurology. 2019 ; Vol. 93, No. 13. pp. e1312-e1323.
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abstract = "OBJECTIVE: To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). METHODS: An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. RESULTS: Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy. CONCLUSIONS: Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.",
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T1 - Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

AU - Cooperative International Neuromuscular Research Group

AU - Hoffman, Eric P.

AU - Schwartz, Benjamin D.

AU - Mengle-Gaw, Laurel J.

AU - Smith, Edward C.

AU - Castro, Diana

AU - Mah, Jean K.

AU - McDonald, Craig M.

AU - Kuntz, Nancy L.

AU - Finkel, Richard S.

AU - Guglieri, Michela

AU - Bushby, Katharine

AU - Tulinius, Mar

AU - Nevo, Yoram

AU - Ryan, Monique M.

AU - Webster, Richard

AU - Smith, Andrea L.

AU - Morgenroth, Lauren P.

AU - Arrieta, Adrienne

AU - Shimony, Maya

AU - Siener, Catherine

AU - Jaros, Mark

AU - Shale, Phil

AU - McCall, John M.

AU - Nagaraju, Kanneboyina

AU - van den Anker, John

AU - Conklin, Laurie S.

AU - Cnaan, Avital

AU - Gordish-Dressman, Heather

AU - Damsker, Jesse M.

AU - Clemens, Paula R.

PY - 2019/9/24

Y1 - 2019/9/24

N2 - OBJECTIVE: To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). METHODS: An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. RESULTS: Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy. CONCLUSIONS: Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

AB - OBJECTIVE: To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD). METHODS: An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. RESULTS: Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy. CONCLUSIONS: Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

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