Gordonville

Researchers are evaluating the pharmacokinetics and safety of risdiplam in infants with spinal muscular atrophy (SMA) who are less than 20 days old at their first dose. This Phase II, open-label study focuses on how the drug behaves in the body and monitors any safety concerns in this very young population. The study is sponsored by Hoffmann-La Roche and targets newborn infants diagnosed genetically with 5q-autosomal recessive SMA or identified through newborn screening or prenatal testing. Participants will receive risdiplam orally once daily at a dose of 0.15 mg/kg for 28 days. The treatment period is straightforward, with all infants receiving the same study drug without placebo or comparator groups. Caregivers may be asked to consider feeding tube placement if necessary to ensure safe hydration, nutrition, and treatment delivery during the study. During the study, researchers will collect blood samples to measure plasma concentrations of risdiplam and analyze key pharmacokinetic parameters such as area under the curve (AUC), steady-state concentration, and free fraction of the drug. Safety will be closely monitored through assessing adverse events up to 30 days after the last dose, including serious events and treatment discontinuations due to side effects. The total observation period may last up to 58 days. This detailed monitoring aims to provide important information on how risdiplam is processed and tolerated in newborns with SMA.

Researchers are conducting the WiTNNess study to document the natural course and variations of muscle disease caused by changes in the TNNT1 gene. This observational study focuses on autosomal recessive TNNT1-associated muscle disease, including infantile-onset and childhood-onset nemaline rod myopathy. The study aims to identify meaningful outcome measures for future clinical trials evaluating new disease-modifying therapies. WiTNNess welcomes children and adults worldwide to participate. The study has two groups: a prospective cohort and a cross-sectional cohort. The prospective group enrolls participants shortly after diagnosis during early infancy and follows them over time with repeated assessments until they reach the primary study outcome. The cross-sectional group includes participants who join at any time after diagnosis and contribute data during a single assessment. Assessments may occur at home, the Clinic for Special Children, or partnering sites, depending on participant needs. Participants undergo various assessments such as vital signs, physical exams, growth measurements, motor milestone documentation, and blood tests. Some may have non-invasive heart ultrasound and chest X-rays. Those in the prospective cohort have ongoing follow-up, while cross-sectional participants provide information once. The primary outcome measured is event-free survival over up to 15 years, with secondary outcomes including motor milestones and thriving. The study involves close monitoring to understand disease progression under current treatments.