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| Name | Class |
|---|---|
| University of Pittsburgh | OTHER |
| Cooperative International Neuromuscular Research Group | NETWORK |
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This long-term extension study is an open-label, multiple-dose study to evaluate the long-term safety, tolerability, efficacy and PD of vamorolone administered once daily by liquid oral suspension over a Treatment Period of 24 months to young boys with DMD who participated in the VBP15-002 Phase IIa and VBP15-003 Phase IIa extension core studies.
This study will evaluate if it is safe to use a new medication called vamorolone for more than two weeks in children with DMD, if boys with DMD who take the study medication have improved muscle function compared to boys with DMD in other studies who did not take any type of steroid, and to see if boys with DMD who take the study medication gain less weight compared to boys with DMD in a prior study who took another type of steroid called prednisone. Enrolled participants will take the study medication for 24 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Level Group 1 | Experimental | Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day. |
|
| Dose Level Group 2 | Experimental | Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day. |
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| Dose Level Group 3 | Experimental | Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day. |
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| Dose Level Group 4 | Experimental | Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vamorolone 0.25 mg/day/day | Drug | Oral administration of 0.25 mg/kg/day daily for 24 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24- month Treatment Period, in boys ages 4-7 years with DMD; Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination); | 24 months |
| Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24-month Treatment Period, in boys ages 4-7 years with DMD. Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination). | 24 Months |
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Inclusion Criteria:
Exclusion Criteria:
Note: Subjects may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating.
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| Name | Affiliation | Role |
|---|---|---|
| Paula R Clemens, MD | University of Pittsburgh | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Davis | Davis | California | 95616 | United States | ||
| University of Florida |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32956407 | Result | 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. | |
| 35076703 |
| Label | URL |
|---|---|
| Link to publication | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level Group 1 | Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day. Vamorolone 0.25 mg/day/day: Oral administration of 0.25 mg/kg/day daily |
| FG001 | Dose Level Group 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 3, 2018 | Sep 26, 2019 |
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| Vamorolone 0.75 mg/day/day | Drug | Oral administration of 0.75 mg/kg/day daily for 24 months. |
|
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| Vamorolone 2.0 mg/day/day | Drug | Oral administration of 2.0 mg/kg/day daily for 24 months. |
|
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| Vamorolone 6.0 mg/day/day | Drug | Oral administration of 6.0 mg/kg/day daily for 24 months. |
|
|
| Gainesville |
| Florida |
| 32611 |
| United States |
| Nemours Children's Hospital | Orlando | Florida | 32827 | United States |
| Ann & Robert H. Lurie Children's Hospital | Chicago | Illinois | 60611 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75207 | United States |
| Royal Children's Hospital | Melbourne | Australia |
| Sydney Children's Hospital | Westmead | Australia |
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| Schneider Children's Medical Center | Petah Tikva | 49202 | Israel |
| Queen Silvia Children's Hospital | Gothenburg | 41685 | Sweden |
| Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | NE7 7DN | United Kingdom |
| Derived |
| 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. |
Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
Vamorolone 0.75 mg/day/day: Oral administration of 0.75 mg/kg/day daily
| FG002 | Dose Level Group 3 | Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day. Vamorolone 2.0 mg/day/day: Oral administration of 2.0 mg/kg/day daily |
| FG003 | Dose Level Group 4 | Participants enrolled in Dose Level Group 5 will receive vamorolone 6.0 mg/kg/day. Vamorolone 6.0 mg/day/day: Oral administration of 6.0 mg/kg/day daily |
| COMPLETED |
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| NOT COMPLETED |
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Subjects entered this study in one of 4 dose level groups, but were allowed to escalate/de-escalate during the course of the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level Group 1 | Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day. Vamorolone 0.25 mg/day/day: Oral administration of 0.25 mg/kg/day daily |
| BG001 | Dose Level Group 2 | Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day. Vamorolone 0.75 mg/day/day: Oral administration of 0.75 mg/kg/day daily |
| BG002 | Dose Level Group 3 | Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day. Vamorolone 2.0 mg/day/day: Oral administration of 2.0 mg/kg/day daily |
| BG003 | Dose Level Group 4 | Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day. Vamorolone 6.0 mg/day/day: Oral administration of 6.0 mg/kg/day daily |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24- month Treatment Period, in boys ages 4-7 years with DMD; Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination); | All subjects who receive at least one dose of vamorolone study medication in the study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments. | Posted | Count of Participants | Participants | 24 months |
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| ||||||||||||||||||||||||||||||||||||||
| Primary | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24-month Treatment Period, in boys ages 4-7 years with DMD. Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination). | All subjects who receive at least one dose of vamorolone study medication in the study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments. | Posted | Number | Events | 24 Months |
|
Adverse events, including Serious Adverse Events (SAEs), and concomitant medications will be assessed at each study visit and recorded throughout the 24 months treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level Group 1 | Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day. Vamorolone 0.25 mg/day/day: Oral administration of 0.25 mg/kg/day daily | 0 | 11 | 0 | 11 | 4 | 11 |
| EG001 | Dose Level Group 2 | Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day. Vamorolone 0.75 mg/day/day: Oral administration of 0.75 mg/kg/day daily | 0 | 23 | 1 | 23 | 14 | 23 |
| EG002 | Dose Level Group 3 | Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day. Vamorolone 2.0 mg/day/day: Oral administration of 2.0 mg/kg/day daily | 0 | 38 | 0 | 38 | 29 | 38 |
| EG003 | Dose Level Group 4 | Participants enrolled in Dose Level Group 4 will receive vamorolone 4.0 mg/kg/day. Vamorolone 4.0 mg/day/day: Oral administration of 4.0 mg/kg/day daily | 0 | 3 | 0 | 3 | 1 | 3 |
| EG004 | Dose Level Group 5 | Participants enrolled in Dose Level Group 5 will receive vamorolone 6.0 mg/kg/day. Vamorolone 6.0 mg/day/day: Oral administration of 6.0 mg/kg/day daily | 0 | 41 | 1 | 41 | 39 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Myoglobinuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear Pain | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Chest Pain | General disorders | MedDRA | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Ear Infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Upper respiratory tract infection | General disorders | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA | Systematic Assessment |
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| Lipids Abnormal | Investigations | MedDRA | Systematic Assessment |
| |
| Joint Injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Limb Injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Body Tinea | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Medical device site pain | General disorders | MedDRA | Systematic Assessment |
| |
| Medical device site rash | General disorders | MedDRA | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Eric Hoffman | ReveraGen BioPharma Inc. | 301-762-7980 | ericphoffman@gmail.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 21, 2019 | Apr 27, 2021 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 17, 2018 | Sep 26, 2019 | ICF_001.pdf |
| 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 |
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| Male |
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| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Sweden |
|
| United States |
|
| United Kingdom |
|
| Israel |
|
| Australia |
|
| OG003 | Dose Level Group 4 | Participants enrolled in Dose Level Group 4 will receive vamorolone 4.0 mg/kg/day. Vamorolone 4.0 mg/day/day: Oral administration of 4.0 mg/kg/day daily |
| OG004 | Dose Level Group 5 | Participants enrolled in Dose Level Group 5 will receive vamorolone 6.0 mg/kg/day. Vamorolone 6.0 mg/day/day: Oral administration of 6.0 mg/kg/day daily |
|
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