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

Phase 2

Completed

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: Vamorolone

• Registration Number: NCT05185622
• Lead Sponsor: Santhera Pharmaceuticals

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2021-11-09
• Study First Submitted QC: 2021-12-22
• Study First Posted: 2022-01-11
• Study Start: 2022-03-21
• Primary Completion: 2024-07-16
• Study Completion: 2024-07-16
• Results First Submitted: 2025-07-03
• Status Verified: 2025-09
• Results First Submitted QC: 2025-10-09
• Last Update Submitted: 2025-10-09
• Results First Posted: 2025-10-24
• Last Update Posted: 2025-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 54

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Group 1	Vamorolone	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.
Treatment Group 2	Vamorolone	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.
Treatment Group 3	Vamorolone	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.
Treatment Group 4	Vamorolone	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.
Treatment Group 5	Vamorolone	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.
Treatment Group 6	Vamorolone	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.
Treatment Sub-Group 7	Vamorolone	Patients in Treatment Sub-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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	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	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.
Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	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	Drug related Adverse Events are TEAEs whose Causality were labeled as 'DEFINITE', 'POSSIBLE' or 'PROBABLE
Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	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	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.
Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)	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 (SAEs through 30 days after final dose of study drug)	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
Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation	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	Adverse Events leading to Study treatment discontinuation
Change in Height (Absolute) From Baseline to Week 12	Baseline, 12 weeks	Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18.
Change in Height (Z-score) From Baseline to Week 12	Baseline, 12 weeks	Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher height).
Change in Weight (Absolute) From Baseline to Week 12	Baseline, 12 weeks	Body weight will be assessed at each of the scheduled time points.
Change in Weight (Percentile) From Baseline to Week 12	Baseline, 12 weeks	Body weight will be assessed at each of the scheduled time points.
Change in Height (Percentile) From Baseline to Week 12	Baseline, 12 weeks	Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18.
Change in Weight (Z-score) From Baseline to Week 12	Baseline, 12 weeks	Body weight will be assessed at each of the scheduled time points. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher weight).
Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12	Baseline, Week 12	Body Mass Index is a measure of weight adjusted for height.
Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12	Baseline, Week 12	Body Mass Index is a measure of weight adjusted for height.
Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12	Baseline, Week 12	Body Mass Index is a measure of weight adjusted for height. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher BMI).
Change in Diastolic Blood Pressure	Day 1, Week 2, Week 6, Week 12, Week 16	Change from Baseline to Week 12 in diastolic sitting blood pressure.
Change in Systolic Blood Pressure	Day 1, Week 2, Week 6, Week 12, Week 16	Change from Baseline to Week 12 in systolic sitting blood pressure.
Number of Participants With Treatment Emergent Cushingoid Features	Baseline through Week 16	Treatment emergent cushingoid features based on physical examination at all baseline, on-treatment and post-treatment assessments
Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result	Day 1, Week 6, Week 12, Week 16	Each subject had blood drawn and urine collected for the standard hematology, chemistry and lipids clinical laboratory tests. In addition, fasting glucose and insulin, morning cortisol, as well as, in the additional 12 to \<18 years age group, LH, FSH, TSH, FT4 were collected. HbA1c determination had also to be performed if urine glucose was positive and/or fasted glucose levels was above normal limits. Any treatment-emergent clinically significant abnormal laboratory test result was reporte
Categorical Analysis of QTcF at Week 12	Baseline, Week 12	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.
Number of Eyes With Cataract	Baseline - Week 12	Cataract was diagnosed by the presence of partial or complete opacity of the crystalline lens at Baseline and Week 12.
Number of Eyes With Glaucoma	Baseline - Week 12	Glaucoma was diagnosed by ocular pressure at Baseline and Week 12.

Secondary Outcome Measures

Name	Time	Method
Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2	Day 1, 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.
Descriptive Statistics of PK Parameters - Tmax	Day 1, Week 2	Tmax is the time to reach the maximum observed concentration collected during a dosing interval
Descriptive Statistics of PK Parameters - Cmax	Day 1, Week 2	Cmax is the maximum observed concentration
Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6	Day 1, Week 2	AUC 0-6 is the area under the concentration-time curve during the first 6 hours after dosing
Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf	Day 1, Week 2	AUC 0-8 is the area under the concentration-time curve after dosing extrapolated to infinity

Trial Locations

Locations (5)

Alberta's Children Hospital; 🇨🇦 Calgary, Alberta, Canada

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Montreal Childrens Hospital; 🇨🇦 Montreal, Canada