Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy
Abstract Introduction Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients’ physical f...
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Adis, Springer Healthcare
2024-11-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-024-00685-8 |
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| author | Craig M. McDonald Jacob S. Elkins Sai Dharmarajan Katherine Gooch Teofil Ciobanu Claire J. Lansdall Alexander P. Murphy Fiona McDougall Eugenio M. Mercuri Ivana Audhya the EMBARK Study Group |
| author_facet | Craig M. McDonald Jacob S. Elkins Sai Dharmarajan Katherine Gooch Teofil Ciobanu Claire J. Lansdall Alexander P. Murphy Fiona McDougall Eugenio M. Mercuri Ivana Audhya the EMBARK Study Group |
| author_sort | Craig M. McDonald |
| collection | DOAJ |
| description | Abstract Introduction Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients’ physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers’ perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively). Methods In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers’ impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses. Results MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90–2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30–1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase). Conclusion These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD. Trial Registration Number ClinicalTrials.gov identifier, NCT05096221. |
| format | Article |
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| institution | Kabale University |
| issn | 2193-8253 2193-6536 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Adis, Springer Healthcare |
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| series | Neurology and Therapy |
| spelling | doaj-art-a60619baea5b4744af8b45640ce0f62a2025-01-26T12:58:46ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362024-11-0114121122510.1007/s40120-024-00685-8Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular DystrophyCraig M. McDonald0Jacob S. Elkins1Sai Dharmarajan2Katherine Gooch3Teofil Ciobanu4Claire J. Lansdall5Alexander P. Murphy6Fiona McDougall7Eugenio M. Mercuri8Ivana Audhya9the EMBARK Study GroupUniversity of CaliforniaSarepta Therapeutics, Inc.Sarepta Therapeutics, Inc.Sarepta Therapeutics, Inc.F. Hoffmann-La Roche Ltd.F. Hoffmann-La Roche Ltd.F. Hoffmann-La Roche LtdGenentechPediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCSSarepta Therapeutics, Inc.Abstract Introduction Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients’ physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers’ perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively). Methods In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers’ impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses. Results MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90–2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30–1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase). Conclusion These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD. Trial Registration Number ClinicalTrials.gov identifier, NCT05096221.https://doi.org/10.1007/s40120-024-00685-8CaregiverDelandistrogene moxeparvovecDuchenne muscular dystrophyGene therapyGlobal Impressions scale |
| spellingShingle | Craig M. McDonald Jacob S. Elkins Sai Dharmarajan Katherine Gooch Teofil Ciobanu Claire J. Lansdall Alexander P. Murphy Fiona McDougall Eugenio M. Mercuri Ivana Audhya the EMBARK Study Group Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy Neurology and Therapy Caregiver Delandistrogene moxeparvovec Duchenne muscular dystrophy Gene therapy Global Impressions scale |
| title | Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy |
| title_full | Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy |
| title_fullStr | Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy |
| title_full_unstemmed | Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy |
| title_short | Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy |
| title_sort | caregiver global impression observations from embark a phase 3 study evaluating delandistrogene moxeparvovec in ambulatory patients with duchenne muscular dystrophy |
| topic | Caregiver Delandistrogene moxeparvovec Duchenne muscular dystrophy Gene therapy Global Impressions scale |
| url | https://doi.org/10.1007/s40120-024-00685-8 |
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