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.

Researchers are evaluating the safety and expression of a gene transfer therapy called delandistrogene moxeparvovec in males with Duchenne Muscular Dystrophy (DMD). This open-label Phase 1 study aims to assess how well the gene therapy works in producing dystrophin protein, which is important for muscle function. Enrollment for most study groups has been completed, with one group currently enrolling new participants. The study can last up to 156 weeks for each participant. Participants will receive a single intravenous infusion of delandistrogene moxeparvovec on the first day of the study. Different cohorts within the trial include ambulatory and non-ambulatory participants of various ages, some on stable steroid doses and others not using steroids. The study monitors participants for effects on dystrophin expression and safety outcomes over time, including liver function and antibody levels. During the study, participants will undergo motor assessments and have samples collected to measure dystrophin protein levels using methods like western blot and immunofluorescence. Researchers will also track adverse events and monitor for infections or liver injury up to 156 weeks. The study includes detailed evaluations at baseline and specific weeks, with safety and biological markers closely observed throughout the participation period.

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 tolerability of BMN 351, an anti-sense oligonucleotide drug, in boys aged 4 to 10 with Duchenne Muscular Dystrophy (DMD) who have a genetic mutation suitable for exon 51 skipping. This Phase 1/2, open-label, multi-center trial aims to evaluate increasing doses of BMN 351 and monitor its effects and safety in this specific group. Participants will be assigned to one of four groups called cohorts. Cohort 1A participants will first receive escalating doses every two weeks for up to 8 weeks, then move to weekly dosing for up to 89 weeks. Cohort 1B, 2, and 3 will receive low, medium, or high doses once weekly for up to 97, 73, or 48 weeks respectively. BMN 351 is given intravenously during these treatment periods. Throughout the study, participants will have safety assessments for up to 97 weeks, including monitoring for adverse effects and laboratory tests. Pharmacokinetic samples of BMN 351 will be collected from plasma, urine, and muscle about every 8 weeks. The study includes evaluations of heart and lung function at baseline and ongoing safety follow-up. The total estimated participation time varies by cohort and dosing schedule.

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 (mNIS+7) 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 multicenter, prospective observational study to understand the natural history of Charcot-Marie-Tooth Disease, Type 4J (CMT4J), a rare neurodegenerative and neuromuscular condition confirmed by specific genetic testing. The study will enroll 20 participants of any age who have a molecularly confirmed diagnosis of CMT4J. The purpose is to collect detailed health information and disease progression data over time, without providing any investigational treatments. Participants will follow a uniform protocol with visits scheduled every 12 months plus a 4-week window, for up to 2 years. At each visit, researchers will collect demographic and medical history data, perform physical and neurological exams, standard lab tests, and use several disease outcome measures. Additional assessments may include neuropsychological tests, nerve conduction studies, muscle MRI, pulmonary function tests, and scoliosis x-rays. Early termination visits are planned if participants leave before completing the study. Throughout the study, participants will undergo thorough evaluations to monitor their condition and collect data relevant to CMT4J progression. This includes clinical exams, imaging, lab tests, and questionnaires. Researchers will use this information to study disease patterns and outcomes over the 2-year follow-up period. No investigational products are administered, and visits may be unscheduled if necessary with approval. Participants are expected to comply with study procedures and travel requirements.

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 studying the effects of a gene therapy called SGT-003 in ambulant male children aged 7 to 11 years with Duchenne Muscular Dystrophy (DMD). This Phase 3, double-blind, placebo-controlled trial aims primarily to assess the impact of a single intravenous infusion of SGT-003 on the time it takes participants to rise from a supine position. Secondary goals include evaluating other efficacy and safety outcomes related to muscle function and respiratory measures. Participants will be randomly assigned to one of two groups: one receives SGT-003 first followed by placebo, and the other receives placebo first followed by SGT-003. Each participant will receive a single intravenous infusion during each of the two study parts. After these infusions, participants will be followed for at least five years in a long-term follow-up phase to monitor ongoing effects. Throughout the trial, participants will undergo assessments of muscle function, including walking and stair climbing speeds, and breathing capacity at baseline and after treatment periods. Researchers will also measure microdystrophin protein levels in tissue samples. Safety will be monitored through adverse event tracking and heart monitoring tests like electrocardiograms and echocardiograms. Overall participation will last several years to observe long-term outcomes.

Researchers are evaluating the safety, tolerability, and effectiveness of a single intravenous infusion of SGT-003 gene therapy in males with Duchenne Muscular Dystrophy (DMD). This open-label, non-randomized, multicenter study includes five age-based cohorts ranging from newborns to 17 years old. The study aims to gather both short-term and long-term data on this genetic treatment, with participant enrollment for older cohorts depending on data from younger groups. Participants will receive one intravenous dose of SGT-003 on Day 1, with the dose and eligibility based on age and ambulatory status. Cohorts include ambulatory boys aged 4 to under 7 years, 7 to under 12 years, and 12 to under 18 years; non-ambulatory boys aged 10 to under 18 years; and children from birth to under 4 years regardless of ambulatory status. After infusion, all participants will be followed for a total of five years to monitor long-term effects. During the study, participants will undergo various assessments including muscle biopsies, physical function tests like the 10-meter walk/run and stair climb, laboratory tests, and heart monitoring through ECG and echocardiography. Researchers will track changes in microdystrophin protein levels and physical abilities over time, along with monitoring for any treatment-related side effects. The long follow-up period allows for thorough safety and efficacy evaluation of SGT-003 gene therapy.