Morrisville

Researchers are evaluating CRD-4730, an oral drug, in a Phase 2 clinical trial involving adults with Catecholaminergic Polymorphic Ventricular Tachycardia CPVT. This study aims to assess the safety, tolerability, pharmacokinetics PK, and pharmacodynamics PD of CRD-4730. Participants will be part of a randomized, double-blind, placebo-controlled crossover study to better understand how CRD-4730 affects CPVT symptoms and treatment responses. Participants will be randomly assigned to one of three sequences in a 3-period crossover design. Each participant will receive two different doses of CRD-4730 and one matching placebo dose in a random order. The study includes multiple dosing periods where participants take tablets of CRD-4730 or placebo, allowing researchers to compare the effects and tolerability of different doses against placebo. During the trial, participants will undergo various assessments to monitor safety, drug levels, and effects on their condition from baseline to Day 101. The study involves close monitoring of heart function and other health measures, with outcome evaluations occurring at multiple timepoints. This will help researchers understand how the drug behaves in the body and its impact on CPVT symptoms, with the trial lasting several months to complete all study periods and follow-ups.

Researchers are evaluating the safety, tolerability, effectiveness, and how the body processes and responds to osivelotor in people with sickle cell disease SCD. This multicenter, Phase 23 study focuses on both adults and adolescents with SCD, aiming to determine the best dose and assess the drugs effects over time. The study has three parts. Part A tests safety, tolerability, and dose-finding in adults with SCD, starting with randomization to different daily doses of osivelotor, ranging from 100 mg to potentially 200 mg, over 12 weeks. Part B compares osivelotor to placebo in adults and adolescents over 48 weeks, with adults receiving an initial 300 mg daily dose for 7 days followed by 150 mg daily, while adolescent dosing will be defined later. The Open Label Extension OLE offers long-term open-label osivelotor treatment for up to two years after Part B. Participants will be monitored throughout the study with regular visits to assess safety, blood responses, and how well they tolerate the medication. The main results will be reviewed through 12 weeks in Part A, 48 weeks in Part B, and approximately 24 months in the OLE. The study includes blood tests, monitoring of vaso-occlusive crises, and other health evaluations to understand osivelotors effects and safety over time.

Researchers are evaluating the efficacy and safety of HBS-301 in adults aged 18 years and older who have idiopathic hypersomnia IH, a condition marked by excessive daytime sleepiness EDS. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to better understand how HBS-301 affects symptoms of IH including sleep inertia, fatigue, and cognitive complaints. Participants will be assigned to receive either HBS-301 tablets or matching placebo tablets once daily in the morning upon waking during an 8-week double-blind treatment period. Following this, there is an optional one-year open-label extension where all participants may receive HBS-301. The study begins with a screeningbaseline period lasting up to 28 days and concludes with 30 days of safety follow-up after treatment. During the trial, participants will undergo various assessments including the Epworth Sleepiness Scale to measure daytime sleepiness, the Idiopathic Hypersomnia Severity Scale, Sleep Inertia Questionnaire, and other patient-reported outcome measures. Researchers will monitor changes in fatigue, cognitive function, quality of life, work productivity, and side effects throughout the study and extension period. Total participation may last up to about 16 months including safety follow-up.

This research aims to evaluate the effectiveness and safety of zanidatamab combined with a physicians choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer who have either progressed on or cannot tolerate previous trastuzumab deruxtecan T-DXd treatment. Zanidatamab has shown promising results against various HER2-positive advanced tumors, including metastatic breast cancer, and may serve as a potential treatment option for these patients. The study also investigates patient-reported tolerability and physical functioning, as well as the pharmacokinetics and immune response to zanidatamab with chemotherapy. Participants will be randomly assigned to receive either zanidatamab or trastuzumab, each given by intravenous infusion alongside one of several chemotherapy options chosen by the physician eribulin, vinorelbine, gemcitabine, or capecitabine the latter is taken orally. Treatment will be administered according to the assigned group, and the study is open-label and multicenter, designed to compare these two treatment combinations in this patient population. During the study, participants will undergo regular assessments to monitor disease progression using imaging criteria RECIST version 1.1, evaluate survival, treatment response, and duration of response. Safety and side effects will be tracked through adverse event reporting and patient questionnaires on symptoms and physical function. Blood samples will be collected to study drug levels and immune reactions. Participants will be followed until disease progression, death, or for up to approximately 44 months for key outcomes, with overall survival monitored for up to about 80 months.

Researchers are evaluating clemizole hydrochloride EPX-100 as an additional treatment for children and adults with Dravet syndrome DS, a severe form of epilepsy. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to assess the safety and effectiveness of clemizole hydrochloride in reducing seizures. The study includes participants with confirmed DS who continue to have seizures despite other treatments and have a documented SCN1A genetic mutation. Participants first undergo a 4-week Observational Period to establish baseline seizure activity. Then, they enter a 16-week Double-Blind Period where they receive either clemizole hydrochloride or a placebo as an oral solution. Following this, eligible participants who complete the double-blind phase may continue to an Open-Label Extension Period, receiving clemizole hydrochloride for up to 3 years. During the study, participants are regularly monitored for changes in countable motor seizures per 28 days and other seizure-related outcomes. Assessments include clinical evaluations and seizure tracking, with safety monitored throughout the trial. The primary outcome focuses on seizure reduction over 16 weeks, while secondary outcomes evaluate seizure frequency, seizure-free days, and clinical impressions of improvement. Participants are followed for up to approximately 172 weeks, ensuring long-term safety and efficacy data are collected.

Researchers are evaluating the effectiveness and safety of pitolisant in treating excessive daytime sleepiness EDS in patients aged 6 years and older with Prader-Willi syndrome. This Phase 3, randomized, double-blind, placebo-controlled, global study also aims to assess how pitolisant affects irritable and disruptive behaviors, hyperphagia, and other behavioral problems such as social withdrawal, stereotypic behavior, hyperactivity, noncompliance, and inappropriate speech. The study includes up to a 45-day screening and baseline period followed by a double-blind treatment phase where participants are randomly assigned to receive either pitolisant tablets or placebo once daily in the morning. In-person visits occur on Days 29, 57, and 77 during this period. Afterward, participants may choose to enter an optional open-label extension period with pitolisant, which includes visits on Days 113, 260, and 441. Follow-up visits are scheduled 15 and 30 days after the final dose in both the double-blind and extension phases. Participants will be closely monitored through various assessments including patient-reported sleep impairment scales, caregiver and clinical impressions of sleepiness and behavior, and questionnaires measuring hyperphagia and other behavioral issues. Safety is monitored by tracking treatment-emergent adverse events throughout the study. The total participation duration may extend over a year for those in the open-label extension, with multiple visits and follow-ups to evaluate the study outcomes comprehensively.

Researchers are evaluating the investigational drug volixibat for treating itching pruritus caused by Primary Biliary Cholangitis PBC, a liver disease. This Phase 2 clinical trial aims to learn more about volixibats effects on itching and its potential impact on PBC disease progression. The study is sponsored by Mirum Pharmaceuticals, Inc. Participants are randomly assigned to one of several groups receiving either volixibat capsules at doses of 20mg or 80mg twice daily, or placebo capsules without the active drug, also taken twice daily. The trial includes two parts, with some participants receiving volixibat 20mg twice daily and others receiving matching placebo capsules. The study is double-blind, meaning neither participants nor researchers know which treatment is given. During the study, participants itching levels are monitored using the Adult Itch Reported Outcome questionnaire over 28 weeks. Researchers also assess quality of life, fatigue, sleep disturbance, liver function tests, bile acid levels, and adverse events. Participants will attend regular visits for assessments, and the main outcome measured is the change in daily itch scores from baseline to week 28. The study excludes healthy volunteers and focuses on adults aged 18 years and older with confirmed PBC.

This research aims to evaluate whether administering XEMBIFY every two weeks alongside Standard Medical Treatment SMT over a one-year period can reduce the number of major bacterial infections each year in adults with low antibody levels hypogammaglobulinemia who have B-cell Chronic Lymphocytic Leukemia CLL, Multiple Myeloma MM, or Non-Hodgkin Lymphoma NHL. The study compares this treatment to a placebo plus SMT to determine its impact on infection rates. Participants are randomly assigned to one of two groups. One group receives a loading dose of XEMBIFY subcutaneously at 150 mgkgday for five consecutive days starting in Week 1, followed by biweekly doses of 300 mgkg until Week 51. The other group receives a placebo injection on the same schedule. Both groups continue to receive the standard medical treatments and supportive care they require throughout the study. During the study, participants will have regular assessments including monitoring the frequency of infections, hospitalizations, and antibiotic use. Researchers will measure the annual rate of major bacterial infections and track the time to first infection among other outcomes up to Week 51. Participants are observed closely throughout the treatment year to evaluate safety and effectiveness, with the entire study lasting approximately one year per participant.

Researchers are evaluating the efficacy and safety of pegtibatinase treatment compared with placebo in people aged 12 to 65 years who have classical homocystinuria HCU due to cystathionine beta synthase deficiency. This phase 3, randomized, blinded, placebo-controlled study includes participants who continue to have elevated total homocysteine tHcy levels despite receiving standard care. The goal is to better understand the impact of pegtibatinase on reducing tHcy levels in this population. Participants will be randomly assigned to receive either pegtibatinase or a placebo administered subcutaneously twice weekly during a 24-week blinded treatment period. Before treatment, participants undergo a screening process lasting up to 10 weeks, including an initial screening and a pre-treatment diet standardization period of up to 6 weeks to stabilize protein intake and supplement use. After the treatment period, a 4-week safety follow-up is conducted for those not continuing in the long-term extension study. During the study, participants diet and compliance with HCU-related treatments are closely monitored using a specialized diet tool. Study visits, including some home visits for drug administration and possible remote visits, occur regularly. The primary measurement is the change in plasma tHcy levels from baseline during weeks 6 to 12, with secondary measurements extending to weeks 16 to 24. Safety and treatment adherence are continually assessed throughout the study duration, which can last up to 38 weeks in total.

Researchers are conducting an observational study to understand the safety of BIIB141, also called omaveloxolone or SKYCLARYS, in people with Friedrichs Ataxia FA who took this drug during pregnancy andor breastfeeding. The study aims to assess any risks to the mother and baby, including major and minor birth defects, maternal complications, and health effects on the baby up to one year after birth. This research will collect health information without changing participants regular medical care. Participants include women with FA exposed to omaveloxolone anytime from shortly before conception through pregnancy and breastfeeding up to one year after their baby is born or until weaning. The study involves collecting both new and past data from participants routine healthcare visits. The study will last at least 10 years to gather comprehensive information about pregnancy outcomes and infant health. During the study, researchers will monitor various outcomes such as the number of major and minor birth defects, gestational diabetes, pre-eclampsia, fetal loss, premature birth, infant growth and development, hospitalizations, and infections. Participants will join after consenting and remain in the study for up to one year after their childs birth unless they choose to leave earlier. The study collects data from routine care visits and does not involve administering any treatment.