Myotonic Dystrophy

Researchers are evaluating the safety and tolerability of multiple doses of an investigational medicine called PGN-EDODM1 in adults with myotonic dystrophy type 1 (DM1). This randomized, double-blind study compares PGN-EDODM1 to a placebo to better understand its effects on this condition. The study is a Phase 2 trial sponsored by PepGen Inc and aims to assess how well participants tolerate the treatment and monitor any adverse events. Participants will be randomly assigned to receive either ascending doses of PGN-EDODM1 or a placebo, both given by intravenous infusion once every 4 weeks for a total of 12 weeks. The treatment period spans these 12 weeks during which doses are administered and safety is closely monitored. The placebo group receives saline infusions on the same schedule to provide comparison data. During the study, participants will be regularly assessed for safety by tracking any adverse events from the start through day 112. Researchers will also measure how the drug behaves in the body, including plasma concentration and half-life, as well as changes in muscle function and myotonia using video hand opening time, hand grip strength, and 10 meter walk/run tests. Muscle biopsies will be performed to study tissue changes. The entire participation period includes baseline assessments, treatment, and follow-up evaluations lasting up to about 112 days.

Researchers are studying the safety, tolerability, and preliminary effectiveness of a drug called IBD0333 in patients with locally advanced or metastatic solid tumors or non-Hodgkin lymphoma. The study includes dose escalation, dose expansion, and clinical exploration phases to find the best dose and explore how well the drug works in specific tumors. Additional goals include understanding how the drug behaves in the body and its immune effects, as well as exploring biomarkers that might predict response to treatment. This is an open, non-randomized phase I/II trial where patients receive IBD0333 during different study phases. The dose escalation phase determines the maximum tolerated dose and dose limiting toxicity over about one year. The dose expansion phase evaluates the recommended phase 2 dose and safety. During the clinical exploration phase, preliminary efficacy and immunogenicity are assessed. Treatment is given according to study protocols designed to evaluate safety and effectiveness. Participants will undergo regular assessments including monitoring for side effects, laboratory tests for organ function, imaging to evaluate tumor response, and blood tests to study drug levels and immune reactions. Researchers will track outcomes such as tumor response rate, duration of response, and progression-free survival over about one year. Safety and tolerability will be closely observed throughout the study. Total participation time may vary depending on individual treatment and follow-up schedules.

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 evaluating the safety, tolerability, and how the body processes and responds to VX-670 in adults with Myotonic Dystrophy Type 1 (DM1). This study is a Phase 1/2 trial that compares different doses of VX-670 to placebo in people diagnosed with DM1 who have a confirmed genetic test showing a specific repeat in their DNA. Participants will be randomly assigned to receive either single or multiple doses of VX-670 or matching placebo. The study has two parts: Part A focuses on single ascending doses, while Part B includes both single and multiple ascending doses. The dosing levels in Part B will be based on results from Part A. Both VX-670 and placebo are given as intravenous solutions. During the study, participants will be monitored for adverse events up to 42 days in Part A and 168 days in Part B to assess safety and tolerability. Researchers will measure drug concentrations in blood plasma and muscle at various time points, including baseline, days 15, and 120. Muscle biopsies will be used to analyze changes in gene splicing. The total participation duration varies by study part, with detailed monitoring of drug effects and safety throughout.

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 evaluating the safety and tolerability of a single intravenous infusion of AB-1003 gene therapy in adults diagnosed with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). This study includes sequential dose-level groups to carefully assess the effects of the treatment. The trial is a two-part, multicenter study with randomized, double-blind, placebo-controlled design to ensure reliable results for adults aged 18 to 65 with confirmed FKRP gene mutations linked to LGMD2I/R9. Participants receive a single intravenous infusion of AB-1003 at one of two dose levels or a placebo in the first part of the study. This dose-escalation phase helps to monitor safety and tolerability before moving to the next phase. The treatment is given as one infusion only, and participants are monitored closely for any side effects or adverse events throughout the study period. During the study, participants will undergo regular evaluations including monitoring for adverse events for up to 52 weeks. Assessments include clinical exams, laboratory tests, and imaging to track the participants’ health and response to the infusion. Safety monitoring is a key focus, with detailed attention to heart function and liver and kidney health. Participants are expected to comply with study procedures and contraception use as required, with the overall study duration spanning approximately one year.

Researchers are evaluating SAR446268, an adeno-associated viral vector-mediated gene therapy, in male and female participants aged 10 to 55 years with non-congenital myotonic dystrophy type 1 (DM1). This Phase 1/Phase 2 open-label, single-arm study aims to assess the safety and effectiveness of SAR446268 in reducing dystrophia myotonica protein kinase (DMPK) mRNA levels and improving neuromuscular function in people with DM1. Participants will receive a single intravenous infusion of SAR446268. The study consists of two parts: Part A, a dose escalation phase with single ascending doses in three cohorts and an optional fourth cohort, and Part B, a dose expansion phase treating additional participants at the identified safe and effective dose. Each participant's involvement lasts approximately 112 weeks, including an optional pre-screening, about 8 weeks of screening, and a 104-week follow-up period after treatment. Throughout the study, participants will undergo various assessments, including muscle biopsies to measure DMPK mRNA levels and RNA splicing index at 12 and 52 weeks post-treatment. Neuromuscular function will be evaluated using tests like the 10-meter walk-run, hand opening time for myotonia, and bilateral hand grip strength at multiple time points. Researchers will also monitor the presence of the viral vector in urine, saliva, and semen samples at intervals after administration. Safety will be tracked by recording any adverse events up to 52 weeks following therapy.

Researchers are studying how different levels of fatigue during power training affect strength, movement, and muscle function in healthy older adults aged 65 to 85 years. The study aims to understand the immediate and recovery effects of varying fatigue levels on muscle soreness, exercise effort, and physical performance to help design safer and more effective training programs for this age group. Participants will complete three supervised power-training sessions on a pneumatic leg press machine about one week apart. Each session involves 4 sets with different fatigue levels: stopping when movement speed drops by 10% (low fatigue), stopping at 30% speed loss (moderate fatigue), or performing cluster sets with rest breaks to match the volume of the moderate fatigue session while maintaining low fatigue. Movement speed is continuously monitored during exercise. During the study, participants undergo strength and mobility tests before and after exercise, provide small blood samples to measure physiological responses, rate exercise effort, and report muscle soreness up to two days post-exercise. Researchers will measure outcomes like maximum voluntary contraction, torque development, muscle activity, muscle oxygenation, blood markers, functional performance tests, perceived exertion, and delayed muscle soreness over multiple timepoints. Participants are monitored for safety and recovery throughout the trial, which lasts about three weeks in total.

This research aims to evaluate the safety and effectiveness of acute transcranial direct current stimulation in patients with systemic autoimmune myopathies, a group of diseases that mainly affect skeletal muscles. These diseases vary widely, and this study addresses the lack of previous research on using this stimulation technique in such patients. The study is designed as a prospective, randomized, double-blind, placebo-controlled trial to rigorously test this approach. Participants will be assigned randomly to one of two groups: one receiving transcranial direct current stimulation and the other receiving a placebo session. The stimulation involves placing two electrodes on the head, targeting the primary motor cortex, with a mild electric current delivered for 20 minutes while the patient is seated. This procedure will be repeated once daily for three days. The placebo group will not receive the actual stimulation. During the study, participants will be monitored closely for safety by checking for any treatment-related side effects shortly after stimulation and again after eight weeks. Researchers will also assess muscle disease activity, muscle strength, patient and physician evaluations, and blood muscle enzyme levels before, shortly after, and at 3 and 8 weeks post-stimulation. The study lasts for several weeks with multiple assessments to understand the treatment's impact and safety over time.