A Study to Assess Vamorolone in Boys Ages 2 to <4 Years a... | NCT05185622

NCT05185622

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

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 4-8 week open-label Dose-tapering Period (starting from Weeks 13) 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 -8 week open label Dose tapering Period during which the dose of study medication will be progressively reduced and discontinued.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Group 1	Experimental	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
Treatment Group 2	Experimental	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
Treatment Group 3	Experimental	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
Treatment Group 4	Experimental	Patients in Treatment Group 4 must be ages 7-<18 years and must be steroid untreated at entry. Treatment Group 4 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.	Drug: Vamorolone
Treatment Group 5	Experimental	Patients in Treatment Group 5 must be ages 7-<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 5 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study.

Name	Type	Description	Arm Group Labels	Other Names
Vamorolone	Drug	Oral administration of vamorolone for 12 weeks.	Treatment Group 1 Treatment Group 2 Treatment Group 3 Treatment Group 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Any 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.	From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	Drug related Adverse Events are TEAEs whose Causality were labeled as 'DEFINITE', 'POSSIBLE' or 'PROBABLE	From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	Severe or medically significant but not immediately life -threatening: hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; incapacitating with inability to work or perform normal daily activity.	From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	A Serious Adverse Event (SAE) is defined as any AE regardless of causality that meets any of the following criteria: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of an existing hospitalization Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions Results in a congenital anomaly/birth defect Is an important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above

Secondary Outcomes

Measure	Description	Time Frame
Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2	The plasma concentration of vamorolone was measured on Day 1 and Week 2 predose, and 1h, 2h and 6h postdose and also 4h and 8h post in the 7-18 year groups.	Day 1, Week 2
Descriptive Statistics of PK Parameters - Tmax

Other Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in Bayley-III Gross Motor Scale (Ages 2 to <4 Years Only)	The Bayley-III Gross Motor scale is a functional assessment, 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.	Baseline, Week 12

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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;
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;
Subject is male, 2 to <4 years or 7 to <18 years of age at time of enrollment in the study;
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];
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];
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];
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;
Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

Exclusion Criteria:

Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
Subject has current or history of chronic systemic fungal or viral infections;
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;
Subject has a history of primary hyperaldosteronism;
Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
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];
Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
Subject has used idebenone within 4 weeks prior to enrollment;
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 enrollment) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
Subject is taking (or has taken within 3 months prior to enrollment) any medication indicated for DMD, including Exondys51, Exondys53, Exondys45, Viltepso and Translarna;
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 enrollment;
Subject has previously been enrolled in the VBP15-006 study or any other vamorolone study.

Contacts/Locations Module

Name	Affiliation	Role
Jean K Mah, M.D.	Alberta Children's Hospital Research Institute, University of Calgary	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Alberta's Children Hospital		Calgary	Alberta	AB T3B 6A8	Canada
British Columbia Children's Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
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.
32956407

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	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. Vamorolone: Oral administration of vamorolone for 12 weeks.
FG001	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. Vamorolone: Oral administration of vamorolone for 12 weeks.
FG002	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. Vamorolone: Oral administration of vamorolone for 12 weeks.
FG003	Treatment Group 4	Patients in Treatment Group 4 must be ages 7-<18 years and must be steroid untreated at entry. Treatment Group 4 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study. Vamorolone: Oral administration of vamorolone for 12 weeks.
FG004	Treatment Group 5	Patients in Treatment Group 5 must be ages 7-<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 5 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study. Vamorolone: Oral administration of vamorolone for 12 weeks.
FG005	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. Vamorolone: Oral administration of vamorolone for 12 weeks.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00010 subjects FG00110 subjects FG0026 subjects FG0036 subjects FG0046 subjects FG00516 subjects
COMPLETED		FG00010 subjects FG00110 subjects FG0026 subjects FG0036 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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. Vamorolone: Oral administration of vamorolone for 12 weeks.
BG001	Treatment Group 2

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

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 Any 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.

Safety set

Posted

Count of Participants

Participants

From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed

ID	Title	Description
OG000	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. Vamorolone: Oral administration of vamorolone for 12 weeks.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. Vamorolone: Oral administration of vamorolone for 12 weeks.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Vomiting	Gastrointestinal disorders		Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders		Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr Shabir Hasham	Santhera	+41 61 906 89 50		Shabir.Hasham@santhera.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 11, 2023	Jul 3, 2025	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jun 25, 2024	Jul 3, 2025	SAP_001.pdf

Submission Tracking

Condition Browse Module

ID	Term
D020388	Muscular Dystrophy, Duchenne
D009136	Muscular Dystrophies

ID	Term
D020966	Muscular Disorders, Atrophic
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009468	Neuromuscular Diseases

Intervention Browse Module

ID	Term
C584811	VBP15 compound

Masking Info

Treatment Sub-Group 7

EG0000 affected10 at risk

EG0010 affected10 at risk

EG0020 affected6 at risk

EG0031 affected6 at risk

EG0040 affected6 at risk

EG0050 affected16 at risk

EG0000 events0 affected10 at risk

EG0011 events1 affected10 at risk

EG0020 events0 affected6 at risk

EG0030 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected16 at risk

eyeOG00018
eyeOG00119
eyeOG00212
eyeOG00312
eyeOG00412
eyeOG00532

eyeOG00018
eyeOG00119
eyeOG00212
eyeOG00312
eyeOG0048
eyeOG00519

OG00412.000± 49.3356

OG005-34.933± 42.1485

OG004631.833± 155.3621

OG005273.000± 335.4937

OG00431.700± 11.6915

OG00516.546± 9.1486

OG004318.850± 99.0038

OG005149.671± 106.2874

OG005-0.254± 0.3909