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Atherosclerotic plaques are fatty build-ups in arteries that can develop silently over time but may eventually narrow or block blood vessels. This condition can lead to serious cardiovascular events like heart attacks or strokes, resulting in many deaths annually. While controlling risk factors such as diabetes and high blood pressure helps reduce risk, some people still develop dangerous plaques. Research shows that plaques with thin caps, soft centers, or tiny new blood vessels are more likely to rupture. New imaging techniques aim to detect these vulnerable plaques earlier for better treatment. This research evaluates a special 3D ultrasound probe and machine designed to capture many images of carotid artery plaques, potentially visualizing whole plaques more accurately than current 2D ultrasound. Participants will receive an infusion of a microbubble contrast agent called SonoVue® to help highlight blood vessels within plaques. Initial 2D ultrasound images locate plaques, followed by contrast-enhanced ultrasound (CEUS) images and then 3D imaging with the new probe. The 3D scan takes 2-5 minutes and may involve multiple image acquisitions. During the study, participants will be cannulated for contrast infusion and undergo ultrasound imaging of their carotid arteries. Researchers will analyze images to detect new tiny blood vessels inside plaques. The main outcome measured is the detection of carotid plaque neovascularization at baseline. The study includes adults over 18 who have already participated in a related trial and have carotid plaques visible on ultrasound. Safety measures include monitoring for contrast allergies and pregnancy status.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of WVE-007, a stereopure siRNA oligonucleotide, in adults living with overweight or obesity. This Phase 1 study focuses on adults aged 18 to 60 years who have a body mass index (BMI) between 28 and 35 kg/m2, aiming to understand how the drug behaves and is tolerated when given in increasing single doses. Participants will receive ascending single subcutaneous doses of WVE-007 or placebo under a randomized, double-blind, placebo-controlled design. The study carefully monitors the effects of these doses to assess safety and how the body processes the drug. The treatment period includes administration of the drug and observation for any reactions or effects, with dose adjustments as planned. Throughout the study, participants will undergo medical history reviews, physical exams, and clinical lab tests to monitor health status and any adverse events from the first day through the end of the study. The main measurement is the proportion of participants experiencing adverse events. This study helps inform the safety profile and biological activity of WVE-007 in adults with overweight or obesity over the course of the trial.

This research focuses on pediatric participants aged 6 to 17 years with obesity or overweight conditions. Its aim is to establish a framework to evaluate the safety and effectiveness of drug treatments for managing chronic weight issues in this population. The study is part of a Phase 3 Master Protocol that includes multiple interventions and will report results when all intervention-specific arms finish. Participants may receive either Orforglipron, a drug given orally, or a placebo, also taken by mouth. Different intervention-specific arms may begin independently as new treatments become available for testing. The study sets clear entry criteria for newly enrolled participants across these intervention arms. During the study, researchers will monitor participants from baseline up to 72 weeks, focusing on the number of participants allocated to each intervention arm. They will also track safety and treatment effectiveness. Participation involves regular assessments of weight, health status, and any side effects, ensuring a thorough evaluation of the chronic weight management interventions over time.

Researchers are evaluating the effectiveness and safety of pirtobrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study focuses on two parts: Part 1 tests three different doses of pirtobrutinib in participants who have had 1 to 3 prior treatments, including a covalent Bruton tyrosine kinase (BTK) inhibitor. Part 2 evaluates pirtobrutinib alone in participants who have not received prior treatment but have a specific genetic deletion called 17p. This is a phase 2, open-label, randomized study. Pirtobrutinib is given orally to participants in both study parts. Participants in Part 1 receive one of three dose levels, while those in Part 2 receive pirtobrutinib monotherapy. Part 1 participation lasts about 3 years, and Part 2 participation can last up to 2 years. The study compares the effects of different doses and treatment histories to better understand pirtobrutinib’s impact on CLL/SLL. Throughout the study, researchers monitor participants' overall response to treatment from the start up to 3 years. They assess safety and side effects, and participants are required to be able to swallow oral medication and have a performance status that allows them to participate. The study includes regular evaluations to determine how well the treatment controls the disease and to track any adverse events over the course of the study periods.

Researchers are studying how combining two medicines, cagrilintide and NNC0480-0389, affects stomach-related side effects in women who are overweight or obese. This Phase 1 trial compares the combination of these drugs to cagrilintide alone. Both medicines are new and being tested to help people with type 2 diabetes and overweight or obesity. The trial medicines are not yet approved for use outside of clinical trials. Participants will receive weekly injections under the skin. In one study period, they will get both cagrilintide and NNC0480-0389, and in the other period, they will receive cagrilintide with a placebo that looks like NNC0480-0389 but has no active medicine. The study lasts about 4.5 months, with each participant going through both treatment periods to compare effects. During the study, researchers will monitor participants closely for stomach-related side effects such as nausea, vomiting, and diarrhea from the first dose until the end of treatment. They will also check medical history, physical exams, vital signs, ECGs, and lab tests to ensure safety. The main outcome is to count treatment-emergent adverse events related to these side effects over the treatment periods.

Researchers are evaluating the effects of orforglipron, an oral medication taken once daily, compared to a placebo in adolescents with obesity or those who are overweight with related health issues. This Phase 3 study aims to assess the medicine's safety, how it is processed in the body, and how well it works over a period lasting about 18 months. Participants include adolescents aged 12 to 17 years who have struggled to lose weight despite previous diet and exercise programs. Participants will be randomly assigned to receive either orforglipron or a placebo, both taken by mouth once daily. The study will monitor changes in body mass index (BMI) from the start of the trial to week 72. Those in the study must meet specific criteria related to their BMI percentiles and presence of weight-related conditions such as hypertension, type 2 diabetes, prediabetes, dyslipidemia, obstructive sleep apnea, or certain liver diseases. During the study, participants will be regularly evaluated through medical assessments that include measuring BMI and monitoring overall health and safety. Researchers will track how the body responds to orforglipron and observe any side effects. The study's total length of participation is approximately 18 months, allowing close follow-up to understand long-term effects and treatment outcomes.

Researchers are evaluating the effectiveness and safety of Afimkibart (RO7790121) as both an induction and maintenance treatment for people with moderately to severely active Crohn's disease in this Phase III, multicenter, double-blind, placebo-controlled study. The goal is to understand how well Afimkibart works compared to placebo in managing symptoms and disease activity over time. Participants will receive either Afimkibart or a matching placebo. Afimkibart is given both as an intravenous infusion and as a subcutaneous injection. This treat-through study means participants continue on the assigned treatment throughout the study period, allowing evaluation of both initial and ongoing therapy effects. During the study, participants will be regularly assessed to measure clinical remission using the Crohn's Disease Activity Index (CDAI) and to check for endoscopic response at week 52. Researchers will monitor safety and treatment effects throughout, with the entire participation lasting up to one year. Assessments include clinical evaluations and endoscopic examinations to track disease changes and treatment impact.

Researchers are studying an experimental drug called ALN-CIDEB in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which are chronic liver conditions caused by excess fat in the liver. The main goal is to assess the safety and tolerability of ALN-CIDEB. The study also explores potential side effects, how the drug affects liver fat content, and the levels of the drug and its byproducts in the blood over time. Participants will receive either ALN-CIDEB or a placebo according to the study protocol. The study includes two parts: Part A focuses on adults with MASLD aged 18 to 55, and Part B involves adults with MASH aged 18 to 65. Treatment dosing schedules and administration details follow the protocol guidelines. The study is randomized, double-blind, and placebo-controlled, designed to evaluate drug safety, pharmacokinetics, and pharmacodynamics. Throughout the study, participants will be monitored for treatment-emergent adverse events up to 48 weeks, including their incidence and severity. Assessments include liver fat content measured by MRI-PDFF and controlled attenuation parameter (CAP) via FibroScan. Stability of other medications is ensured before and during the study. Researchers will also track participants' clinical and laboratory data related to liver function and metabolic health to understand the drug's effects and safety profile.

Researchers are evaluating the safety, effectiveness, and tolerability of upadacitinib in adolescents and adults with severe alopecia areata (AA), a condition where the immune system attacks hair follicles causing hair loss on the head, face, or other body parts. This phase 3 study involves about 1500 participants worldwide and compares upadacitinib to a placebo to assess treatment impact on severe AA. Participants are randomly assigned to one of three groups receiving either upadacitinib or placebo oral tablets once daily for up to 160 weeks. There is a chance for re-randomization at weeks 24 and 52 based on Severity of Alopecia Tool (SALT) scores. Those completing initial studies may join an extension study to receive upadacitinib for up to an additional 108 weeks. Follow-up occurs for 30 days after the last dose. Throughout the study, participants attend regular visits at hospitals or clinics for medical assessments, blood tests, side effect monitoring, and questionnaires. Researchers measure the percentage of participants achieving a SALT score of 20 or less at week 24 and track adverse events up to 164 weeks. The study may involve a higher treatment burden compared to usual care due to frequent visits and evaluations.

Researchers are investigating the dosing and effects of andexanet alfa and its interaction with enoxaparin in healthy adults aged 18 to 55 years. This Phase I, randomized, single-blind, placebo-controlled study aims to better understand how andexanet alfa works alone and in combination with anticoagulant drugs rivaroxaban, apixaban, and enoxaparin. The study includes multiple modules focusing on the reversal effects of andexanet on these anticoagulants and the timing when andexanet no longer affects enoxaparin. Participants will receive treatments including intravenous bolus and infusion of andexanet alfa, oral tablets of rivaroxaban or apixaban, subcutaneous injections of enoxaparin, and placebo given in various forms depending on the module. The study has four modules divided into two parts: Part A focuses on andexanet dosing, and Part B evaluates restarting anticoagulation with enoxaparin. In Module 3, only an andexanet bolus is given without infusion. The study involves a screening and enrollment period of up to 28 days, followed by a stay at the study site for safety baseline labs from Day -3 to Day -1, treatment from Day 1 to Day 2, safety follow-up from Day 3 to Day 5, and a final follow-up visit within 30 days after the last treatment. Outcomes measured include anti-Factor Xa activity, thrombin generation potential, and time to onset of coagulation. Safety labs and assessments will be performed throughout to monitor participants' health and treatment effects.