Achondroplasia

Researchers are evaluating the effectiveness and safety of once-weekly subcutaneous doses of navepegritide at 100 micrograms per kilogram compared to a placebo in adolescents aged 12 to 18 years with Achondroplasia. The main focus is to measure the annualized growth velocity after a 52-week treatment period. Participants will receive either navepegritide or a placebo through weekly injections under the skin for one year. The study is randomized, double-blinded, and placebo-controlled, ensuring that neither the participants nor the researchers know who receives the active medication or placebo during the 52 weeks. During the trial, participants will be monitored regularly to assess growth and other health parameters. Researchers will measure growth rates and height z-scores over the course of the year. Safety and any side effects will be closely observed throughout the study. The trial is sponsored by Ascendis Pharma A/S and aims to provide detailed information about the effects of navepegritide in this adolescent population.

Researchers are evaluating the safety, tolerability, and effectiveness of Navepegritide (TransCon CNP) in infants with genetically confirmed achondroplasia (ACH) who are younger than 2 years old. This Phase 2, multicenter, double-blind, randomized, placebo-controlled trial aims to compare weekly doses of Navepegritide with a placebo over a 52-week period to understand its impact on growth and safety in this population. Participants receive once-weekly subcutaneous injections of either 100 bcg/kg Navepegritide or a placebo for 52 weeks. The study is randomized in a 2:1 ratio, with some infants receiving the active drug and others receiving placebo injections. After the 52-week treatment period, there is an open-label extension phase allowing continued evaluation. During the study, infants will be monitored through medical history reviews, physical exams, vital signs, ECGs, imaging, and lab tests to evaluate safety and growth changes. The main outcomes measured are the safety and tolerability of Navepegritide and its effect on growth over 52 weeks. Parents or caregivers will administer weekly injections and follow study instructions, including vitamin D supplementation where applicable. The total participation time includes the initial 52 weeks of treatment followed by further observation during the extension period.

This research aims to observe and track growth patterns and the clinical progression of Hypochondroplasia (HCH) in children. It focuses on collecting various growth measurements and other relevant data over time to better understand this condition. The study is sponsored by BioMarin Pharmaceutical and involves children diagnosed with Hypochondroplasia, up to 15 years old. Participants include children confirmed to have Hypochondroplasia through genetic testing. The study is observational, meaning there are no experimental treatments involved. Children will be monitored regularly to record changes in growth and body proportions, with data collection occurring every six months over the course of the study, which may last up to 15 years. Throughout the study, children will undergo assessments every six months to measure growth velocity, height, body mass index (BMI), and body segment ratios. Quality of life and severity impressions from both patients and caregivers will be evaluated annually. Researchers will also track medical events, use of growth hormone treatments, and any limb lengthening surgeries. This long-term follow-up allows for comprehensive monitoring of growth and health outcomes in children with Hypochondroplasia.

Researchers are conducting an observational study to gather detailed information about children with achondroplasia (ACH), a form of dwarfism. The study aims to collect data on body measurements, clinical features, related medical conditions, quality of life, and treatments over a period ranging from 6 months to 2 years. The study also evaluates the safety, tolerability, and appropriate dosing of an oral medication called ABSK061, as well as its effects on growth and disease burden in children with ACH. Participants aged 2.5 to under 11 years old, who have a confirmed diagnosis of ACH through genetic testing, will be observed without any interventions. The study will monitor changes in growth parameters such as annualized growth velocity, standing height, sitting height, and their ratios. Additionally, researchers will assess how well children accept the ABSK061 minitablets taken orally. The study includes safety evaluations and pharmacokinetic and pharmacodynamic assessments of the medication. During the study, children's growth and health will be regularly measured every three months for up to two years. Assessments include physical measurements, clinical evaluations, and monitoring for ACH complications. Researchers will observe how the disease progresses naturally and how the oral medication ABSK061 influences growth and disease-related factors. The study ensures ongoing safety monitoring and allows participants to be ambulatory and capable of standing without assistance throughout the observation period.

Researchers are evaluating the safety, tolerability, and potentially effective doses of TYRA-300, a fibroblast growth factor receptor 3 (FGFR3) selective tyrosine kinase inhibitor, in children aged 3 to 10 years with achondroplasia who have open growth plates. This Phase 2, multicenter, open-label dose-escalation study includes three groups of children: the Sentinel Safety Cohort, Cohort 1, and Cohort 2. The study aims to understand how TYRA-300 affects growth velocity and related measurements over time. Participants receive TYRA-300 as sprinkle capsules or mini-tablets, with doses calculated based on each child's weight. Weight adjustments occur every three months to ensure appropriate dosing. The study features multiple dosing levels from 0.125 mg/kg up to 0.50 mg/kg, with dose escalations based on specific protocol criteria. The study spans up to 12 months for primary outcomes, with additional assessments at 6 and 12 months for secondary growth and pharmacokinetic measures. Throughout the study, children will undergo regular evaluations including growth measurements such as height, arm length, tibial and femur length, and arm span proportionality. Safety is monitored by tracking treatment-related adverse events according to established criteria. Pharmacokinetic assessments will measure how the drug is absorbed and processed. The total participation duration includes up to one year of treatment and observation to assess changes in growth and safety outcomes under medical supervision.

Researchers are evaluating the safety and effects of daily vosoritide treatment compared to placebo in infants and young children with hypochondroplasia (HCH), aged from birth up to less than 36 months. This Phase 2, randomized, double-blind, placebo-controlled, multicenter study aims to better understand vosoritide's impact on growth and health over one year in this specific young population with genetically confirmed HCH. Participants will be randomly assigned to receive either vosoritide or a placebo through daily subcutaneous injections for 52 weeks. The vosoritide dose will be adjusted based on weight bands approved for a related condition. After treatment, there will be a 2-week safety follow-up to monitor any adverse effects or changes. During the study, participants will have regular evaluations including clinical lab tests, heart rate, respiratory rate, blood pressure, and body temperature measures at several time points. Researchers will assess growth changes such as height, body segment ratios, and bone density using scans, along with monitoring adverse events and vosoritide blood levels. The total participation duration is about 54 weeks including treatment and safety follow-up.

Researchers are creating an electronic registry to collect detailed clinical information from patients with achondroplasia, a rare bone condition. Initially focused on U.S. patients, this registry aims to support research on health outcomes and treatment options by gathering data from prenatal stages through the most recent medical encounters. The registry is longitudinal, allowing for both retrospective and ongoing data entry over time. The registry is housed in a secure, web-based database called RedCap, designed for multi-site academic research collaboration. It is maintained by the Greenberg Center for Skeletal Dysplasias at Johns Hopkins and involves co-investigators from several U.S. institutions. Each co-investigator can enter and access data for their own patients, with deidentified information shared across sites to enable analysis. The goal is to enroll at least 1,500 patients and support research questions through shared data. Participants' clinical data, including growth measurements and surgical history, are collected through chart reviews over a period of at least three years. The registry tracks detailed phenotypic data while protecting patient identity through password protection and data backup. This observational study allows researchers to better understand the natural history and treatment outcomes of achondroplasia by examining the collected data longitudinally.

Researchers are evaluating advanced surgical simulation techniques for correcting complex skeletal deformities and abnormalities in children, adolescents, and young adults with musculoskeletal disorders. These conditions often involve rare and severe abnormalities in bone, joint, and muscle-tendon development, affecting multiple limbs and presenting challenges in standardizing treatment and predicting outcomes. The study focuses on improving surgical planning and support tools using 3D modeling and printing technologies, aiming to enhance precision, safety, and reproducibility of surgeries. The study involves surgeries to correct bone deformities, supported by preoperative virtual surgical planning and the use of patient-specific instruments created through 3D printing. These include Patient-Specific Instruments (PSI) and Graft-Specific Instruments (GSI), which are designed to improve surgical accuracy. The research is conducted within specialized 3D laboratories at the Musculoskeletal Apparatus Network centers, where surgical simulations and planning procedures are systematically organized and standardized. Participants will undergo assessments including radiological follow-up and clinical-functional evaluations at the time of surgery and after one year. Researchers will measure outcomes such as the degree of skeletal correction achieved, operating room times, fluoroscopy times, blood loss, and any intra- or peri-operative complications. The suitability of the patient-specific instruments and bone grafts will also be evaluated. The study aims to improve surgical quality and efficiency while monitoring participants throughout a one-year period post-surgery.

This research aims to find genetic causes of unexplained congenital skeletal disorders (GSDs) and better understand their natural development and complications. It is a 5-year project involving collaboration among genetic and bone research institutions. The study focuses on participants with unsolved GSD diagnoses, using advanced genetic testing to identify new gene variants and study their effects in cells and animal models. The goal is to improve diagnosis, knowledge of disease mechanisms, and future treatment strategies for skeletal diseases. Participants include a well-characterized group of 300 individuals with GSD, including 120 with unknown diagnoses. Researchers use whole genome sequencing and RNA sequencing to search for molecular causes. Candidate gene variants are selected with support from clinical findings and large genetic databases. The effects of new variants are studied both in laboratory cells and in transgenic mice to understand their role in disease. During the study, data on the genetic changes, clinical features, and complications of different GSD groups are collected and summarized. The project tracks new gene discoveries and gathers information about the natural course of rare skeletal disorders. This information aims to help develop personalized follow-up and treatment plans. Participation involves genetic sample analysis and clinical data review, with an overall focus on advancing scientific knowledge about skeletal diseases over the 5-year period.

Researchers are investigating whether increased consumption of Greek yogurt combined with regular high-impact exercise can improve bone health and reduce inflammation in young competitive athletes aged 15 to 22. The study focuses on male and female varsity and club athletes to see if Greek yogurt offers benefits similar to those from whey protein supplements, which are commonly used by athletes. This research aims to better understand how diet affects bone metabolism during growth and development in young athletes. The study is designed as a randomized controlled trial lasting 24 weeks, beginning with an 8-week control period where participants follow their usual diet and training. Afterward, for 16 weeks, athletes will be randomly assigned to consume either two daily servings of Greek yogurt or whey protein supplements while maintaining their habitual diets. The Greek yogurt servings are 175 g each, and the whey protein servings are 2/3 of a scoop dissolved in water, with flexibility in timing to fit training schedules. Participants will undergo assessments including blood tests at weeks 0, 8, 16, and 24 to measure markers of bone remodeling, inflammation, sex hormones, and growth factors. Bone strength will be evaluated using ultrasound at the same timepoints, and body composition will be measured by bioelectrical impedance analysis. Dietary intake, nutrition knowledge, and physical activity will be regularly tracked using food diaries, questionnaires, and training logs. The study aims to analyze changes in these measures to understand the effects of Greek yogurt versus whey protein on bone health and inflammation in young athletes.