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This study aims to assess safety and effectivness of long-term treatment with vamorolone in boys with Duchenne Muscular Dystrophy (DMD) who have completed prior studies with vamorolone.
All subjects in this study have completed previous studies with vamorolone and continued to receive vamorolone under special programs: Compassionate Use Program [CUP], Named Patient Program [NPP] or Expanded Access Protocol [EAP]. All subjects will continue treatment with vamorolone under Guardian protocol instead. The primary objective of this study is to evaluate the safety of long-term treatment with vamorolone in boys with Duchenne Muscular Dystrophy regarding vertebral fractures. Secondary study objectives will evaluate the safety of long-term treatment with vamorolone on non-vertebral fractures, cataracts, delayed puberty, overall safety as well as ambulatory and non-ambulatory function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| vamorolone | Experimental | On Day 1, Subjects will roll over from a previous vamorolone program and continue treatment with vamorolone under this protocol. During the study, vamorolone will be administered at a dose range between 2 mg/kg/day and 6 mg/kg/day for boys weighing <40 kg. For boys weighing 40 kg or above, the dose range will be 80 mg to 240 mg once daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vamorolone 40 mg/mL oral suspension | Drug | Vamorolone is administered at a dose range between 2 mg/kg/day and 6 mg/kg/day for boys weighing <40 kg. For boys weighing 40 kg or above, the dose range will be 80 mg to 240 mg once daily. Doses can be adjusted within the dose range as determined by the Investigator based on tolerability. The highest tolerated dose should be used. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of vertebral fractures per 1000 person-years based on X-ray central reading. | Lateral thoracolumbar spine X-Rays will be collected and sent to a central reader for evaluation of vertebral fractures | At Enrolment and every 2 years during a Full visit |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first vertebral fractures (cumulative incidence) | From enrolment up to at least 2 years | |
| Number of non-vertebral fractures per 1000 person-years based on investigator reporting | Non-vertebral fractures will be reported by investigators and not reviewed centrally |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Gent (Universitair Ziekenhuis Gent) | Ghent | 9000 | Belgium | |||
| UZ Leuven (Universitair Ziekenhuis Leuven) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36036925 | Background | Guglieri M, Clemens PR, Perlman SJ, Smith EC, Horrocks I, Finkel RS, Mah JK, Deconinck N, Goemans N, Haberlova J, Straub V, Mengle-Gaw LJ, Schwartz BD, Harper AD, Shieh PB, De Waele L, Castro D, Yang ML, Ryan MM, McDonald CM, Tulinius M, Webster R, McMillan HJ, Kuntz NL, Rao VK, Baranello G, Spinty S, Childs AM, Sbrocchi AM, Selby KA, Monduy M, Nevo Y, Vilchez-Padilla JJ, Nascimento-Osorio A, Niks EH, de Groot IJM, Katsalouli M, James MK, van den Anker J, Damsker JM, Ahmet A, Ward LM, Jaros M, Shale P, Dang UJ, Hoffman EP. Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA Neurol. 2022 Oct 1;79(10):1005-1014. doi: 10.1001/jamaneurol.2022.2480. | |
| 38335499 |
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|
|
| From enrolment until up to at least 3 years |
| Time to first non-vertebral fractures (cumulative incidence) | From enrolment until up to at least 3 years |
| Number of cataracts per 1000 person-years based on ophthalmologist assessment | An ophthalmologist assessment including assessment of posterior capsular cataracts by slit lamp will be performed yearly | From enrolment until up to at least 3 years |
| Number of subjects not reaching Tanner stage 2 by 15 years of age | Qualified personnel (eg, an individual, part of the endocrinology team and trained to assess Tanner stages) will provide an assessment of the puberty status of the subject, including testicular volume. | From enrolment until up to at least 3 years |
| Frequency of adverse events (AEs) and serious adverse events (SAEs) | The occurrence of AEs should be sought by questioning of the subject and/or his caregiver at each visit or phone call during the study. All SAEs occurring from signature of the ICF up to 30 days after last dose of study medication must be reported, irrespective of severity or whether or not considered related to study medication. All SAEs must be reported within 24 hours of becoming aware of the event, whether or not the SAE is considered to be related to the study medication. | From enrolment until up to at least 3 years |
| Change from baseline in body weight | Physical examination will include weight (in kg) | From enrolment until up to at least 3 years |
| Number of subjects with clinically relevant laboratory abnormalities | Clinically relevant laboratory abnormalities will include HbA1c and morning cortisol measurements. | From enrolment until up to at least 3 years |
| Change from baseline in Time to Stand (TTSTAND) velocity | The TTSTAND measures the time (in seconds) required for the subject to stand to an erect position from a supine position (floor) | From enrolment until up to at least 3 years |
| Six-minute Walk Test (6MWT) | 6MWT will be performed only in the ambulatory subjects. The total distance traveled, in meters, should be recorded along with the validity of the test as assessed by the test administrator. If a subject cannot complete 6 minutes of walking, the total meters and the time until discontinuation of the test should be recorded. | From enrolment until up to at least 3 years |
| Change from baseline in 6MWT distance | From enrolment until up to at least 3 years |
| Age at ambulatory and non-ambulatory milestones | Ambulatory milestones include Loss of standing from the floor, Loss of ability to climb 4-stairs, Loss of ability to walk 10 meters (loss of ambulation), Loss of ability to stand unassisted. Non-ambulatory milestones include Loss of ability to perform hand-to-mouth function, Loss of ability to use a manual wheelchair, Loss of ability to transfer independently from wheelchair, Nocturnal ventilation and Full time ventilation. | From enrolment until up to at least 3 years |
| North Star Ambulatory Assessment (NSAA) scores | The NSAA is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with DMD and allows to monitor the progression of the disease and treatment effects. | At enrolment and each Full visit (Month 12, 24, 36, etc / End-of -Treatment) until End of Study |
| Change from baseline in body height | Physical examination will include height (in cm). Ulnar length of the non-dominant arm will be used if standing height cannot be measured. | From enrolment until up to at least 3 years |
| Change from baseline in Body Mass Index (BMI) | BMI will be derived based on weight and height at every study visit | From enrolment until up to at least 3 years |
| Leuven |
| 3000 |
| Belgium |
| University Hospital Brno | Brno | Czechia |
| Fakultni Nemocnice Motol | Prague | 150 06 | Czechia |
| Children's Hospital Agia Sofia | Athens | 115 27 | Greece |
| Children's Health Ireland at Tallaght, Tallaght University Hospital | Dublin | D24TN3C | Ireland |
| Schneider Children's Medical Center | Petah Tikva | 4920235 | Israel |
| Leiden University Medical Center | Leiden | 2333 ZA | Netherlands |
| Radboud University Nijmegen | Nijmegen | 6525 HB | Netherlands |
| Te Wao Nui - Child Health Service, Wellington Hospital | Wellington | 6021 | New Zealand |
| Hospital Universitario Puerta de Hierro Majadahonda | Madrid | 28222 | Spain |
| Hospital Universitario y Politecnico de La Fe | Valencia | 46026 | Spain |
| Queen Elizabeth University Hospital | Glasgow | Lanarkshire | United Kingdom |
| Alder Hey Children's Hospital | Liverpool | Merseyside | L14 5AB | United Kingdom |
| Leeds Teaching Hospitals NHS Trust | Leeds | West Yorkshire | LS1 3EX | United Kingdom |
| University Hospitals Birmingham NHS Foundation Trust | Birmingham | B9 5SS | United Kingdom |
| Great Ormond Street Hospital for Children NHS Foundation Trust | London | WC1N 3JH | United Kingdom |
| The John Walton Muscular Dystrophy Research Centre | Newcastle | NE1 3BZ | United Kingdom |
| Background |
| Dang UJ, Damsker JM, Guglieri M, Clemens PR, Perlman SJ, Smith EC, Horrocks I, Finkel RS, Mah JK, Deconinck N, Goemans NM, Haberlova J, Straub V, Mengle-Gaw L, Schwartz BD, Harper A, Shieh PB, De Waele L, Castro D, Yang ML, Ryan MM, McDonald CM, Tulinius M, Webster RI, Mcmillan HJ, Kuntz N, Rao VK, Baranello G, Spinty S, Childs AM, Sbrocchi AM, Selby KA, Monduy M, Nevo Y, Vilchez JJ, Nascimento-Osorio A, Niks EH, De Groot IJM, Katsalouli M, Van Den Anker JN, Ward LM, Leinonen M, D'Alessandro AL, Hoffman EP. Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy: A Randomized Controlled Trial. Neurology. 2024 Mar 12;102(5):e208112. doi: 10.1212/WNL.0000000000208112. Epub 2024 Feb 9. |
| 31451516 | 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. |
| 35076703 | Background | Mah JK, Clemens PR, Guglieri M, Smith EC, Finkel RS, Tulinius M, Nevo Y, Ryan MM, Webster R, Castro D, Kuntz NL, McDonald CM, Damsker JM, Schwartz BD, Mengle-Gaw LJ, Jackowski S, Stimpson G, Ridout DA, Ayyar-Gupta V, Baranello G, Manzur AY, Muntoni F, Gordish-Dressman H, Leinonen M, Ward LM, Hoffman EP, Dang UJ; NorthStar UK Network and CINRG DNHS Investigators. Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2144178. doi: 10.1001/jamanetworkopen.2021.44178. |
| 30219580 | 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. |
| Result | K. Nip, A. de Vera, S. Hasham, P. Charef, S. Wong. An open-label study to collect long-term safety and efficacy data from boys with DMD who have completed prior studies with vamorolone (GUARDIAN Study). Neuromuscular Disorders Volume 43, Supplement 1, October 2024, 104441.298 |
| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C584811 | VBP15 compound |
| D013535 | Suspensions |
| ID | Term |
|---|---|
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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