Duchenne Muscular Dystrophy

Researchers are evaluating the safety, tolerability, and effectiveness of BBM-D101, a gene addition therapy, for boys with Duchenne Muscular Dystrophy DMD. This single-arm, open-label study focuses on boys aged 4 to under 9 years with confirmed DMD gene mutations. BBM-D101 aims to deliver a therapeutic protein to muscle cells that may help support muscle function and prevent muscular dystrophy. Participants will receive a single intravenous infusion of BBM-D101. The study includes an initial 52-week period to assess safety, immune response, pharmacokinetics, and therapeutic effects, followed by a long-term follow-up of up to 5 years to monitor ongoing safety and efficacy. The treatment involves one dose only, with no placebo group. During the study, participants will undergo motor function assessments, muscle biopsy, MRI scans, and laboratory tests including serum creatine kinase levels. Researchers will monitor adverse events and changes in muscle function and biomarkers over time. Follow-up visits will continue for several years to observe long-term effects and safety, with careful tracking of any serious or dose-limiting side effects within the first 12 weeks.

This research aims to evaluate the safety and gene expression of delandistrogene moxeparvovec, a gene transfer therapy, in males with Duchenne Muscular Dystrophy DMD. The study focuses on non-ambulatory participants in Cohort 8, while enrollment for earlier cohorts has been completed. The study is open-label and conducted by Sarepta Therapeutics, Inc., with a maximum participant duration of 156 weeks. Participants will receive a single intravenous infusion of delandistrogene moxeparvovec on Day 1. The study measures dystrophin protein expression at 12 weeks post-infusion, as well as safety outcomes including acute liver injury and other adverse events up to 72 weeks for Cohort 8. Additional assessments monitor vector shedding, antibody levels, treatment-emergent adverse events, and steroid use for up to 156 weeks. During the study, participants undergo various assessments including laboratory tests, biomarker evaluations, and motor function testing. Researchers will collect samples such as urine, saliva, and stool to track vector shedding and measure immune responses. Safety monitoring includes tracking liver-related events and infections. The total study participation may last up to about 3 years, allowing for long-term follow-up of treatment effects and safety.

Researchers are evaluating anitocabtagene autoleucel anito-cel, a BCMA-directed CAR-T cell therapy, in adults with generalized myasthenia gravis GMG classified as MGFA Grade 2 to 4a. This Phase 1 open-label, multi-center study aims to assess the safety, tolerability, and preliminary efficacy of anito-cel in patients who require immunosuppressive therapy as determined by their neurologist. The study focuses on identifying dose-limiting toxicities DLTs, the maximum tolerated dose MTD, and selecting the recommended Phase 2 dose RP2D for treatment. The study includes sequential phases screening, enrollment with leukapheresis to collect cells, pretreatment with a standard lymphodepletion chemotherapy regimen for 5 days, and a single intravenous infusion of anito-cel cells. Optional bridging therapy may be given while the CAR-T cells are prepared. Following infusion, participants will be closely monitored for safety and efficacy outcomes over time. Participants will undergo safety monitoring for at least 28 days after infusion, with safety data collected throughout the study duration of up to 24 months. Clinical effects will be evaluated using measures including the Myasthenia Gravis Activities of Daily Living MG ADL score, Quantitative Myasthenia Gravis QMG score, and Myasthenia Gravis Composite MGC scale. Additionally, blood tests will monitor autoantibody levels and pharmacokinetics of the therapy. This comprehensive follow-up ensures careful assessment of treatment impact and participant health.

Researchers are studying the safety and effectiveness of a single dose of nexiguran ziclumeran NTLA-2001 compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy ATTRv-PN. This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score 7 mNIS7 over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants nerve health and overall well-being.

Researchers are conducting a Phase 3 clinical trial to evaluate the safety and effectiveness of AOC 1044, also known as delpacibart zotadirsen, for treating Duchenne Muscular Dystrophy DMD in boys aged 7 to 16 with specific gene mutations suitable for exon 44 skipping. This study is designed as a randomized, double-blind, placebo-controlled trial to assess the impact of this intravenous treatment on muscle function over time. Participants will be randomly assigned to receive either AOC 1044 or a placebo infusion every 6 weeks for 54 weeks, totaling 9 doses during the double-blind treatment period. After this, all participants can join an open-label extension where they receive AOC 1044 every 6 weeks for another 54 weeks, adding 9 more doses. Following the final dose at week 102, participants will have assessments at weeks 108 and 114 to evaluate safety and treatment effects. During the study, participants will undergo various assessments including tests for time to rise velocity, muscle strength, walking and climbing abilities, and quality of life measures. Muscle enzyme levels and global impressions of severity and change from both patients and caregivers will also be monitored. Safety and tolerability will be reviewed regularly by an independent committee. Overall participation lasts over two years, including screening, treatment, extension, and follow-up phases.

Researchers are studying older adults aged 65 and above who are pre-frail or mildly frail to evaluate the effects of Whole Body Vibration Training WBVT combined with usual care compared to usual care alone. This trial aims to improve muscle mass, strength, and function, addressing the challenges of traditional exercise programs that many older adults find difficult to follow due to physical or cognitive limitations. The study focuses on measuring muscle strength and physical function changes after interventions. Participants will be randomly assigned to one of two groups one group will receive WBVT along with usual care, and the other will receive only usual care. WBVT sessions use the Galileo Vibration machine three times a week for four weeks, progressively increasing vibration frequency, squat angles, and session duration. Both groups will receive instruction on Otago exercises to be done at home, with encouragement to continue aerobic activities like brisk walking. Exercise and falls diaries will be kept for up to three months. Participants will undergo assessments before the intervention, two weeks after, and three months after. These include measurements of knee extension strength, hand grip strength, muscle mass, gait speed, chair stands, calf circumference, physical activity levels, and quality of life. Falls, emergency visits, hospitalizations, and mortality will also be tracked for one year. The study includes surveys and interviews to evaluate feasibility and accessibility, with adherence monitored by reminders and diaries.

Dystrophinopathy refers to a group of X-linked recessive genetic disorders, including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, and X-linked dilated cardiomyopathy. This research aims to understand the clinical characteristics and natural progression of dystrophinopathy by studying patients over time in multiple centers. The goal is to assess clinical and genetic aspects to improve patient care and management. This observational study follows a registered cohort of individuals diagnosed with Duchenne Muscular Dystrophy, including female carriers confirmed by genetic testing or muscle biopsy if genetic confirmation is unavailable. The study does not involve experimental treatments but focuses on collecting detailed clinical and genetic information to observe disease progression. Participants will be monitored over an extended period, with researchers tracking outcomes such as age at death by 20 years. The study involves regular clinical evaluations to gather data on the clinical spectrum and progression of the disease. Long-term follow-up helps optimize management strategies and provides valuable insights into dystrophinopathy.

Researchers are evaluating the efficacy and safety of a single intravenous infusion of SGT-003 gene therapy in ambulatory boys aged 7 to 11 with Duchenne Muscular Dystrophy DMD. This Phase 3, double-blind, placebo-controlled study aims to compare the effects of SGT-003 against placebo and includes long-term follow-up monitoring for at least five years after dosing. The study is designed to assess improvements in motor function and muscle protein levels in this pediatric population. Participants are randomly assigned to one of two groups one group receives SGT-003 first followed by placebo, while the other group receives placebo first followed by SGT-003. Each participant receives a single intravenous infusion during each part of the study. The trial includes two parts, each involving one infusion, and continues with long-term follow-up to monitor outcomes and safety. During the study, participants will undergo various assessments including measurements of motor function such as time to rise from supine position, stride velocity, stair climb speed, and walkingrunning speed. Muscle protein levels and respiratory function will also be evaluated. Safety will be monitored through adverse event tracking and heart function tests like ECG and echocardiography. Overall participation spans the two infusion periods plus a long-term follow-up of at least five years after receiving SGT-003.

Researchers are investigating the safety, tolerability, and potential benefits of a single intravenous infusion of SGT-003 gene therapy in males with Duchenne muscular dystrophy DMD. This multicenter, open-label, non-randomized study includes five age-based cohorts ranging from newborns to adolescents up to 17 years old. The study aims to understand how well this gene therapy works and how safe it is for different age groups affected by this genetic muscle disorder. Participants in each cohort will receive one infusion of SGT-003, a gene therapy containing the human microdystrophin gene, administered intravenously on Day 1. The cohorts are divided by age and ambulatory status, with younger and ambulatory participants in cohorts 1 to 4, and non-ambulatory participants in cohort 5. Cohorts 4 and 5 will begin enrollment only after safety and efficacy data from the earlier cohorts are reviewed. All participants will be followed for a total of 5 years to monitor long-term outcomes. During the study, participants will be monitored for treatment-emergent adverse events and changes in microdystrophin protein levels up to one year after infusion. Additional assessments will evaluate muscle function, including walking speed, stair climbing, and standardized motor scores over time. Safety will be closely tracked through laboratory tests, vital signs, physical exams, and heart monitoring. These evaluations will continue throughout the 5-year follow-up period to understand the lasting effects of the gene therapy.

Researchers are evaluating apitegromab in children younger than 2 years old who have 5q autosomal recessive Spinal Muscular Atrophy SMA and delayed motor milestones linked to SMA or a Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders CHOP-INTEND score below 55. This Phase 2, double-blind study aims to assess how the drug acts in the body pharmacokinetics and pharmacodynamics, its effects on motor function, and its safety and tolerability. Participants will receive apitegromab through intravenous IV infusion every 4 weeks during a 48-week treatment period. All enrolled children must have been treated with an approved SMN1-targeted therapy like onasemnogene abeparvovec-xioi or be currently receiving an approved SMN2-targeted therapy such as nusinersen or risdiplam. The study compares low and high doses of apitegromab alongside these standard SMN therapies. During the study, researchers will monitor apitegromab levels in the body, its biological effects, and motor function improvements over 48 to 52 weeks. Safety and tolerability will also be assessed throughout this time. The trial involves regular assessments including motor function tests and safety evaluations to track progress and any adverse effects. Participation lasts approximately one year, with detailed follow-up to understand the treatments impact.