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| Name | Class |
|---|---|
| Sarepta Therapeutics, Inc. | INDUSTRY |
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This is an 48-week open-label study to determine the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 for the treatment of boys with duchenne muscular dystrophy who have a single exon duplication of either exon 45, 51 or 53, respectively. There will be weekly infusions and two muscle biopsies at baseline and at month 12.
DMD is a rare, serious, debilitating, and ultimately fatal, disease for which there is an urgent need to develop safe and effective therapies. In order to efficiently meet this urgency and the needs of the subject community, the study evaluates the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 administration over approximately 1 year in DMD subjects with duplication mutations amenable to treatment by exon 45, 51 or exon 53 skipping. Skipping of a single copy of the duplicated exon is expected to result in a wild-type (WT) DMD transcript allowing the expression of a WT, full length dystrophin protein. Successful skipping of a single copy of the duplicated exon in in vitro and in vivo models has been reported in the literature. AMONDYS 45, EXONDYS 51, VYONDYS 53 have the potential to be disease-modifying treatments for boys with DMD mutations amenable to exon 45, 51 and exon 53 skipping, respectively.
The totality of the non-clinical data with these PMOs as well as AVI-4225 (targeting exon 23) and EXONDYS 51 suggests that PMOs are well tolerated in the non-clinical setting. Moreover, treatment with EXONDYS 51(at 30 mg/kg and 50 mg/kg) has been well-tolerated by boys with DMD deletion mutations amenable to skipping exon 51. The relatively low expected risk for subjects exposed to AMONDYS 45, EXONDYS 51, VYONDYS 53 and the urgent medical need for a treatment for this subject population support the conclusion that the potential benefits of exposing subjects to AMONDYS 45, EXONDYS 51, VYONDYS 53 outweigh the potential risks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AMONDYS 45 | Experimental | This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon. |
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| EXONDYS 51 | Experimental | This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon. |
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| VYONDYS 53 | Experimental | This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amondys 45 | Drug | This drug is used to target skipping of exon 45 of the dystrophin gene. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen) | This will be assessed by the comparison of quantification of protein in muscle biopsy tissue by western blot from baseline to 1 year post-initiation of treatment. | Baseline, 1 year |
| Monitoring for the Development of Unacceptable Toxicity. | This will be measured by capturing and reviewing Adverse Events as defined by CTCAE v4.0. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen). | This will be assessed by the comparison of immunofluorescent staining in muscle biopsy tissue from baseline to 1 year post-initiation of treatment. | 1 year |
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Inclusion Criteria:
Exclusion Criteria:
Other inclusion/exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Kevin Flanigan, MD | Nationwide Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19156838 | Background | Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ, den Dunnen JT. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 2009 Mar;30(3):293-9. doi: 10.1002/humu.20918. | |
| 24643206 | Background | Greer KL, Lochmuller H, Flanigan K, Fletcher S, Wilton SD. Targeted exon skipping to correct exon duplications in the dystrophin gene. Mol Ther Nucleic Acids. 2014 Mar 18;3(3):e155. doi: 10.1038/mtna.2014.8. |
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| ID | Title | Description |
|---|---|---|
| FG000 | AMONDYS 45 | This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon. AMONDYS 45: This drug is used to target skipping of exon 45 of the dystrophin gene. |
| FG001 | EXONDYS 51 |
| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 20, 2021 |
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| Exondys 51 | Drug | This drug is used to target skipping of exon 51 of the dystrophin gene. |
|
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| Vyondys 53 | Drug | This drug is used to target skipping of exon 53 of the dystrophin gene. |
|
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| 23907995 | Background | Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM; Eteplirsen Study Group. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47. doi: 10.1002/ana.23982. Epub 2013 Sep 10. |
| 26573217 | Background | Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E; Eteplirsen Study Group and Telethon Foundation DMD Italian Network. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016 Feb;79(2):257-71. doi: 10.1002/ana.24555. Epub 2016 Jan 8. |
This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon. EXONDYS 51: This drug is used to target skipping of exon 51 of the dystrophin gene. |
| FG002 | VYONDYS 53 | This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon. VYONDYS 53: This drug is used to target skipping of exon 53 of the dystrophin gene. |
| COMPLETED |
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| NOT COMPLETED |
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We did not enroll any participants in the EXONDYS 51 treatment arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | AMONDYS 45 | This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon. AMONDYS 45: This drug is used to target skipping of exon 45 of the dystrophin gene. |
| BG001 | EXONDYS 51 | This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon. EXONDYS 51: This drug is used to target skipping of exon 51 of the dystrophin gene. |
| BG002 | VYONDYS 53 | This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon. VYONDYS 53: This drug is used to target skipping of exon 53 of the dystrophin gene. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean | Standard Deviation | Years |
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| Sex/Gender, Customized | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen) | This will be assessed by the comparison of quantification of protein in muscle biopsy tissue by western blot from baseline to 1 year post-initiation of treatment. | We did not enroll any participants in the EXONDYS 51 treatment arm. | Posted | Mean | Standard Deviation | Percent of Healthy Control | Baseline, 1 year |
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| Primary | Monitoring for the Development of Unacceptable Toxicity. | This will be measured by capturing and reviewing Adverse Events as defined by CTCAE v4.0. | We did not enroll any participants in the EXONDYS 51 treatment arm. | Posted | Number | Events | 1 year |
| ||||||||||||||||||||||||||||||||||
| Secondary | Change in Dystrophin Expression From Baseline Following Treatment With Either AMONDYS 45 (Previously Casimersen), EXONDYS 51 (Previously Eteplirsen ), or VYONDYS 53 (Previously Golodirsen). | This will be assessed by the comparison of immunofluorescent staining in muscle biopsy tissue from baseline to 1 year post-initiation of treatment. | We did not enroll any participants in the EXONDYS 51 treatment arm. | Posted | Mean | Standard Deviation | % Dystrophin Postive Fibers | 1 year |
|
Data was collected over 1 year.
We did not enroll any participants in the EXONDYS 51 treatment arm.
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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 | AMONDYS 45 | This arm will involve the treatment of boys with DMD who have a duplication of exon 45, for which AMONDYS 45 will target skipping of this exon. AMONDYS 45: This drug is used to target skipping of exon 45 of the dystrophin gene. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG001 | EXONDYS 51 | This arm will involve the treatment of boys with DMD who have a duplication of exon 51, for which EXONDYS 51 will target skipping of this exon. EXONDYS 51: This drug is used to target skipping of exon 51 of the dystrophin gene. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | VYONDYS 53 | This arm will involve the treatment of boys with DMD who have a duplication of exon 53, for which VYONDYS 53 will target skipping of this exon. VYONDYS 53: This drug is used to target skipping of exon 53 of the dystrophin gene. | 0 | 1 | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
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| Decreased Hemoglobin | Blood and lymphatic system disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Procedural Discomfort | General disorders | Systematic Assessment |
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| Kidney Stones | Renal and urinary disorders | Systematic Assessment |
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| Incontinence | Renal and urinary disorders | Systematic Assessment |
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| Bruising | Vascular disorders | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Procedural Discomfort | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Wound Dihiscence | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Laceration | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Correction of a Congenital Defect | General disorders | Systematic Assessment |
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| Non-Procedural Discomfort | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kevin Flanigan, Center for Gene Therapy Director | Abigail Wexner Research Institute, Nationwide Children's Hospital | 614-722-5615 | kevin.flanigan@nationwidechildrens.org |
| Sep 11, 2023 |
| Prot_SAP_000.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 |
|---|---|
| C000718147 | casimersen |
| C000611335 | eteplirsen |
| C000710673 | golodirsen |
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| Female |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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