Riverdale

This research aims to evaluate the safety, tolerability, and impact on albuminuria of the drug MZE829 in adults who have proteinuric chronic kidney disease and carry the APOL1 high-risk genotype. This Phase 2 open-label study focuses on participants with specific genetic markers associated with kidney disease to better understand treatment effects. Participants will receive MZE829 in the form of oral capsules. The study involves monitoring the participants over a 12-week period to assess the drug's safety and how well patients tolerate it. Researchers will also measure changes in albuminuria, which reflects kidney function. During the study, participants will be closely monitored for any adverse events from the first day through week 12. Safety assessments and laboratory tests will be performed to track the drug’s effects. The main goal is to determine how safe and tolerable MZE829 is, along with its impact on kidney disease markers over the treatment duration.

The trial investigates the safety, tolerability, effectiveness, and how the body processes and responds to osivelotor in people with sickle cell disease (SCD). This Phase 2/3, multicenter study involves adults and adolescents with SCD, aiming to find the best dose and compare osivelotor to a placebo. The study also includes a long-term extension to assess ongoing safety and blood-related effects. Osivelotor is given orally as tablets. The study has three parts: Part A focuses on determining a safe and effective dose in adults; Part B compares osivelotor to placebo in adults and adolescents over 48 weeks; and the Open Label Extension (OLE) offers continued treatment to those who completed Part B to monitor long-term safety and responses. Participants will be monitored throughout the study periods with assessments of safety, tolerability, and treatment effects. These include evaluations at 12 weeks (Part A), 48 weeks (Part B), and approximately 24 months after the last participant joins (OLE). Researchers will track blood values, side effects, and disease-related events to understand how the drug works and its impact on SCD over time.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating a new approach to prevent cardiovascular events in patients at increased risk due to age and conditions like type 2 diabetes, prediabetes, or metabolic syndrome but without known symptomatic cardiovascular disease. The study compares a Cleerly Coronary Artery Disease (CAD) Staging System-based care strategy with standard risk factor-based care to see if the former can better reduce cardiovascular events. The Cleerly system uses imaging to visualize and quantify coronary artery disease and guides personalized treatment and education based on this assessment. The trial uses the Cleerly CAD Staging System device, which employs a proprietary algorithm to detect and stage coronary artery disease and generate a risk score to guide treatment decisions. Participants receive either this stage-based care or the usual care based on traditional risk factors. The study is prospective, randomized, and pragmatic, designed to follow patients over an average of 3.5 years to compare cardiovascular event outcomes between these two care approaches. Participants will be monitored through cardiovascular event tracking throughout the study period. Data collected includes imaging results, risk scores, and treatment adherence to evaluate the impact of the care strategies. The primary outcome is the comparison of cardiovascular event risk between the Cleerly stage-based care and risk factor-based care groups. The study also includes ongoing safety monitoring and personalized management by a cardiologist-led team via digital communication devices.

Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) are rare sleep disorders causing excessive daytime sleepiness, making it difficult for people to stay alert during daily activities like school, work, or driving. NT1 often includes sudden muscle weakness called cataplexy triggered by strong emotions, while NT2 does not have cataplexy. People with IH feel tired even after long sleep and may have trouble waking up. This study aims to evaluate the safety, tolerability, and effects of ORX750, a drug designed to mimic orexin, a brain protein that helps keep people awake, in individuals with NT1, NT2, and IH. Participants will be randomly assigned to receive either ORX750 capsules or matching placebo capsules in this Phase 2a trial. The study will compare the drug against placebo to learn about its safety, how the body processes it, and its potential to reduce sleepiness and improve symptoms in these conditions. Participants must stop all other narcolepsy or hypersomnia medications and follow study requirements throughout the trial. During the study, researchers will monitor participants for treatment-related side effects, changes in laboratory tests, vital signs, heart electrical activity (ECG), and any suicidal thoughts or behaviors up to day 35. The main outcomes focus on safety and tolerability of ORX750. The study includes adults aged 18 to 65 years with specific diagnoses of NT1, NT2, or IH and tracks their response and health closely during the trial period.

Researchers are investigating the safety and effectiveness of crizanlizumab compared to a placebo in adolescents and adults aged 12 years and older who have Sickle Cell Disease and experience frequent vaso-occlusive crises (VOCs). This phase III, multicenter, randomized, double-blind study includes patients who have had between 4 and 12 healthcare professional-managed VOCs in the past year. Participants may or may not be taking hydroxyurea or hydroxycarbamide therapy alongside the study treatment. Participants will be randomly assigned in a 2:1 ratio to receive either crizanlizumab at a dose of 5 mg/kg or a placebo, both given as intravenous infusions. The randomization is stratified based on whether they are using hydroxyurea/hydroxycarbamide and by geographic region (South America, North America, and sub-Saharan Africa). Crizanlizumab and placebo are provided in single-use vials for infusion. Treatment will be monitored over a planned period of at least 52 weeks. Throughout the study, participants will be closely monitored for the number of VOCs that require healthcare professional management, including those handled in a healthcare facility or remotely, over one year. Medical history, laboratory tests, and other assessments will be used to document VOCs and evaluate safety. Participants who are on hydroxyurea/hydroxycarbamide or erythropoietin stimulating agents must maintain stable doses during the study. The study aims to assess both the rate of VOCs and the overall safety profile of crizanlizumab in this patient population.

Researchers are evaluating the effects of survodutide in adults aged 18 years and older who have a confirmed liver condition called non-alcoholic steatohepatitis (NASH) or metabolic-associated steatohepatitis (MASH). Eligible participants must have a body mass index (BMI) of 27 kg/m2 or higher, or at least 25 kg/m2 if they are Asian. The study excludes those with other chronic liver diseases or a history of significant alcohol use. The main goal is to see if survodutide can improve liver function and delay progression of liver damage over time. Participants are randomly assigned to receive either survodutide or a placebo, with twice the chance of receiving survodutide. Both treatments are given as weekly injections under the skin using a pre-filled syringe. Alongside treatment, all participants receive regular counseling to encourage healthy diet and exercise habits. The study lasts up to four and a half years, with frequent visits or remote video calls during the first year and five months, then quarterly visits thereafter. During the study, doctors monitor participants' health, including body weight and liver function using imaging tests at certain visits. Participants complete symptom questionnaires to help assess their condition. Researchers track outcomes such as survival, need for liver transplant, worsening liver disease, and liver-related complications. Safety and any side effects are closely watched throughout the study period to understand the treatment's impact.

Researchers are evaluating the effects of survodutide on adults living with obesity who have a liver disease called non-alcoholic steatohepatitis (NASH) or metabolic associated steatohepatitis (MASH), along with moderate or advanced liver fibrosis. The study focuses on whether survodutide can improve liver function and reduce liver damage in these participants. This Phase III trial aims to assess both the effectiveness and safety of survodutide over a long-term period. Participants are randomly assigned to one of two groups: one receiving weekly injections of survodutide and the other receiving placebo injections that look like the medicine but contain no active drug. The doses of survodutide are gradually increased until the target dose is reached. All participants receive counseling to support healthy diet changes and regular exercise throughout the study. The study lasts up to 7 years, with frequent visits to the study site or remote video calls. In the first year, visits occur every 2 weeks, then every 4 to 6 weeks, and later every 3 months alternating between in-person and remote. Throughout the study, researchers monitor participants' health, liver condition through imaging and biopsies, body weight, digestive system effects, and questionnaires about symptoms and quality of life. The main outcomes include liver fibrosis improvement, resolution of MASH without worsening fibrosis, and long-term safety and efficacy measures.

Researchers are evaluating the pharmacokinetics of the tablet formulation Pociredir in adults with Sickle Cell Disease (SCD). The study is designed as a Phase 1, open-label trial that compares the drug's behavior in the body when taken in either a fasted or fed state. The goal is to understand how the presence or absence of food affects the drug's absorption and processing in participants with SCD. The study includes two cohorts: a Fasted Cohort with up to approximately 12 participants who will fast before and after dosing, and a Fed Cohort with up to approximately 12 participants who will consume a high-fat breakfast before dosing. Participants will be admitted to the clinical site the day before dosing, receive a single dose of Pociredir on Day 1, and remain in the clinic for up to 4 days. Water intake is also regulated around dosing. Pharmacokinetic samples will be collected up to 72 hours after dosing to measure various plasma concentration parameters. Participants will undergo screening up to 28 days before dosing and will have in-patient confinement from Day -1 to Day 3, followed by outpatient visits on Days 4 and 8-11 for study completion. Researchers will monitor plasma concentrations of Pociredir and key pharmacokinetic outcomes such as maximum concentration, area under the curve, time to maximum concentration, half-life, clearance, and volume of distribution. Safety and adherence will be observed through clinic visits and laboratory testing during the study period.