Hillsborough

Researchers are evaluating the safety and effectiveness of GTX-102, an antisense oligonucleotide, in people with Angelman syndrome, a genetic condition. This Phase 2 open-label basket study includes participants of various genotypes and ages, divided into four subprotocols (A, B, C, and D), to study different forms and age groups affected by Angelman syndrome. The study aims to observe how GTX-102 works and whether it is safe for both children and adults with this condition. The study includes screening, loading, and maintenance periods for all subprotocols. Subprotocols A, B, and C have a single treatment arm where participants receive GTX-102. Subprotocol D randomly assigns participants in a 2:1 ratio to either receive GTX-102 or no treatment, with both groups following the same visit schedule. After completing the study, participants may choose to continue receiving GTX-102 in a long-term extension study. Participants will undergo various assessments including cognitive testing, safety monitoring for adverse events, and response evaluations using specific outcome measures up to day 506. Regular laboratory tests, magnetic resonance imaging (MRI), lumbar punctures, and adherence to scheduled visits and treatments are required. Researchers will track treatment-emergent adverse events and serious adverse events, as well as cognitive and multidomain responses, to better understand the impact of GTX-102 over time.

This phase 2 study aims to establish proof of concept with the age-appropriate dose of ARGX-119 in ambulant pediatric patients with spinal muscular atrophy (SMA). Despite available treatments, there remains an unmet medical need for patients with SMA. Neuromuscular junction (NMJ) dysfunction contributes to the pathophysiology of SMA, including muscle weakness and fatigability. Activation of muscle-specific kinase (MuSK) by ARGX-119 may stabilize and improve NMJ function in patients with SMA, reducing muscle weakness and fatigability, and improving quality of life.

Researchers are evaluating how well the 20-valent pneumococcal conjugate vaccine (20vPnC) protects adults aged 65 and older who are hospitalized with radiologically-confirmed community-acquired pneumonia (RAD+CAP). The study focuses on pneumonia caused by seven new types of the Streptococcus pneumoniae bacteria included in the 20vPnC vaccine. This observational study uses a test-negative design to compare the presence of these specific bacterial types in vaccinated and non-vaccinated participants. Participants provide a urine sample that is tested with BinaxNOW4 S. pneumoniae and serotype-specific urinary antigen detection (UAD) assays to detect the bacteria and its strains. Cases are defined as participants with pneumonia caused by the seven additional serotypes in 20vPnC beyond those in the 13-valent vaccine, plus serotype 15C. Controls include participants without these vaccine serotypes or with pneumonia caused by other agents. The main diagnostic procedure is the non-invasive urine test, and all participants are hospitalized adults aged 65 or older with pneumonia confirmed by chest imaging. Participants share demographic and medical history information and undergo urine testing during their hospital stay, which typically lasts 1 to 2 days for study procedures. Researchers collect data on illness and hospitalization for up to 30 days through medical chart reviews. The primary outcome measures how effective 20vPnC is against pneumonia caused by the additional serotypes over a 55-month period, helping to understand the vaccine's real-world performance in this older population.

Researchers are studying the effectiveness, safety, and tolerability of ponsegromab combined with standard chemotherapy compared to chemotherapy with placebo in adults who have cachexia and metastatic pancreatic ductal adenocarcinoma. This Phase 2b/3 study includes participants who have already completed initial chemotherapy cycles and aims to evaluate ponsegromab as a first-line treatment option for this condition. The study includes a randomized, double-blind design conducted across multiple centers and countries. Participants will receive either one of two doses of ponsegromab or a placebo, both given alongside standard chemotherapy regimens such as nab-paclitaxel plus gemcitabine or FOLFIRINOX. The study intervention is administered subcutaneously every four weeks. After Phase 2b, one ponsegromab dose will be selected for Phase 3, and participants may continue or switch doses accordingly while maintaining blinding. An optional open-label extension allows participants to receive ponsegromab for up to 12 months after the double-blind study period. During the study, participants will undergo tumor assessments every 6 to 8 weeks by independent radiologists. Researchers will measure body weight changes and anorexia symptoms over 12 weeks to assess treatment impact. The study also includes a caregiver sub-study to explore the quality of life and well-being of primary caregivers. Treatment continues until discontinuation, withdrawal, death, or study completion based on overall survival events.

Researchers are building CureDuchenne Link®, a data hub that collects integrated biospecimens, clinical information, and self- or caregiver-reported data from individuals diagnosed with Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), or carriers of these conditions. This resource supports research by providing a rich set of health and outcomes data combined with biospecimens to enable effective translational studies for neuromuscular disorders. Participants join the study through the CureDuchenne Link™ application, accessible via mobile device or web. Participation can be fully virtual, at project sites, or at community events across the country. The collected data is securely stored in a HIPAA-compliant data warehouse and made available to approved researchers for studies related to DMD, BMD, and other neuromuscular diseases. Participants or their guardians provide consent and share diagnosis and genetic testing results upon entry. The study collects and monitors diagnosis and genetic mutation information. The involvement is flexible and ongoing, with communications about research opportunities and community programs offered through the application, supporting wide participation from individuals age 4 weeks and older.

Researchers are evaluating the effectiveness, safety, and tolerability of zeleciment basivarsen (DYNE-101) for treating myotonic dystrophy type 1 (DM1), a genetic condition confirmed by having a trinucleotide repeat size greater than 100. This Phase 3 study aims to understand how well this treatment works compared to placebo and to monitor any side effects or issues related to the treatment over time. The study includes three periods: an initial screening period lasting up to 8 weeks, followed by a 48-week placebo-controlled treatment phase where participants receive either DYNE-101 or placebo through intravenous (IV) infusion. After this, there is a 24-week long-term extension period. An independent committee will regularly review safety and tolerability data to ensure participant well-being throughout the study. Participants will be assessed on their ability to perform physical tasks such as the 5 Times Sit-To-Stand test at the start and after 49 weeks. Throughout the study, researchers will monitor safety, tolerability, and physical function. The total participation spans over a year including screening, treatment, and extension periods, with careful observation of health status and treatment effects.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating the safety and outcomes of different surgical margin sizes for adults with stage II primary invasive cutaneous melanoma. The trial compares the effects of removing 1 cm versus 2 cm of healthy skin around the melanoma site to see if smaller margins provide similar disease control. This study aims to understand if narrower excision margins can reduce surgery side effects and improve quality of life without increasing the risk of melanoma returning. Participants will be randomly assigned to undergo wide local excision surgery with either a 1 cm or 2 cm margin around the original melanoma scar. Both approaches involve removing an extra margin of skin to eliminate any remaining melanoma cells after the initial biopsy. Surgery is scheduled to be completed within 120 days after diagnosis and within 28 days after randomization. This phase III, multi-center trial will assess if the smaller margin is as effective as the larger one. During the study, patients will be followed for up to 60 months to monitor disease-free survival, which means the length of time without melanoma recurrence. Researchers will also evaluate quality of life, side effects from surgery, and the economic impact on health services. Participants will have regular clinical assessments, and outcomes will be recorded to determine the long-term safety and benefits of the two surgical approaches.

Researchers are evaluating two chemotherapy treatments, mFOLFIRINOX and mFOLFOX, with or without the immunotherapy drug nivolumab, for advanced, unresectable, or metastatic HER2 negative adenocarcinoma of the esophagus, gastroesophageal junction, and stomach. This phase III trial aims to determine whether adding irinotecan to the usual FOLFOX regimen improves overall survival and other outcomes such as progression-free survival, response rates, and treatment tolerability. The study also explores biomarkers like PD-L1 combined positive score and cell free DNA to understand treatment effects better. Participants are randomly assigned to one of two treatment groups. One group receives fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) with nivolumab as needed, while the other group receives fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) with nivolumab as needed. All drugs are given intravenously. Throughout the trial, patients undergo MRI and CT scans and may provide blood samples for additional testing. During the study, participants are closely monitored for overall survival for up to two years after randomization. Researchers assess safety, side effects, and patient-reported outcomes to evaluate treatment tolerability. The trial also tracks progression of disease and response to therapy using imaging and other clinical evaluations. Participation includes regular imaging, blood collection, and completing questionnaires to help understand the impact of these treatments.

Researchers are evaluating surgical and minimally invasive treatments for lumbar spinal stenosis (LSS) by comparing Medicare patients who received the MILD procedure against those who had interspinous process decompression (IPD). The study focuses on outcomes such as the rate of harms related to the initial procedure and the frequency of additional surgical or minimally invasive interventions within 24 months after treatment. Enrollment includes patients treated from January 1, 2017, onward, with continuation until the sponsor decides to stop. The MILD procedure involves percutaneous image-guided lumbar decompression, performed under fluoroscopy through a dorsal approach to partially remove tissue and bone at the affected spinal level. The control group receives the IPD procedure for LSS. Both groups are monitored for a 24-month period post-index procedure using Medicare claims data to track reoperations and any harms. Participants contribute data through Medicare claims without needing prior enrollment or consent, as the study is exempt from IRB oversight. Researchers collect and analyze information on procedure-related harms and subsequent interventions over two years. This approach allows evaluation of long-term safety and effectiveness outcomes for patients treated with either MILD or IPD.