Kaminokawa

Researchers are evaluating the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome, a condition marked by reduced levels of the Nav1.1 protein due to mutations in the SCN1A gene. Zorevunersen is an investigational antisense oligonucleotide designed to increase the expression of the sodium channel Nav1.1 protein by boosting the production of its messenger RNA. This Phase 3, multicenter, randomized, double-blind, sham-controlled study aims to assess the potential of zorevunersen for disease modification by measuring changes in major motor seizure frequency and other health outcomes. The study has two treatment periods. In Treatment Period 1, participants assigned to zorevunersen receive the drug by intrathecal administration on Day 1, Day 57, Day 169, and Day 281 with doses of 70 mg initially and then 45 mg later. The sham group undergoes a procedure mimicking drug administration without receiving the drug. In Treatment Period 2, those initially on zorevunersen receive 45 mg doses on Day 393, Day 477, and Day 589. Participants initially in the sham group are then given zorevunersen doses of 70 mg on Day 393 and Day 477, and 45 mg on Day 589. Participants will be closely monitored throughout the study with a primary focus on seizure changes measured at Week 28. Secondary assessments include behavior, cognition, clinical status, and quality of life. The study includes an initial 8-week baseline period and a 6-week observation period to confirm seizure frequency and stability of other treatments. Patients may continue to an open-label extension study to receive zorevunersen if eligible. The study involves children aged 2 to under 18 years and tracks safety and tolerability alongside efficacy outcomes.

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Researchers are evaluating the effectiveness and safety of KarXT in Japanese adults aged 18 to 65 who are experiencing acute psychotic episodes due to schizophrenia. The study focuses on adults diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) and confirmed by a psychiatric interview. Participants must have a specific range of symptom severity measured by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scale. Participants are randomly assigned to receive either KarXT or a placebo during a 5-week double-blind phase where neither the participants nor the researchers know which treatment is given. After this, there is a 52-week open-label extension where all participants receive KarXT. The doses are specified and administered on set days throughout the study. Throughout the study, researchers monitor changes in schizophrenia symptoms using the PANSS score at week 5 and track any treatment-emergent adverse events up to week 52 during the open-label extension. The study involves regular assessments to ensure safety and effectiveness over both the short and long term, with total participation lasting up to 57 weeks.

This research aims to evaluate the long-term safety and tolerability of brivaracetam in children and adolescents with epilepsy. It includes pediatric participants who previously took part in neonatal or long-term follow-up studies, as well as new participants from Japan with partial-onset seizures. The study also includes evaluation of pharmacokinetics in Japanese participants. It is a Phase 3, open-label, single-arm, multicenter study focusing on pediatric epilepsy patients treated with brivaracetam as an additional therapy. Participants will receive brivaracetam orally twice daily, either as tablets available in 10 mg, 25 mg, or 50 mg strengths, or as an oral solution with a concentration of 10 mg/ml. The treatment is administered in two equal doses each day. The study includes those previously enrolled in related studies and new enrollees from Japan, with treatment and monitoring continuing over an extended period to assess long-term safety. During the study, researchers will monitor participants from the initial evaluation visit through safety visits that may last up to five years. They will track any adverse events related to treatment, including serious events and those causing discontinuation of the drug. Assessments include clinical evaluations, laboratory tests, and electroencephalogram readings, with ongoing safety monitoring to understand how well participants tolerate the medication over time.

Researchers are evaluating ivonescimab as a first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors show high PD-L1 expression. This phase 3 randomized, double-blinded study compares ivonescimab with pembrolizumab to assess overall survival and progression-free survival in this patient group. Participants will receive either ivonescimab or pembrolizumab as intravenous injections. The study is designed to monitor these treatments over time to determine which may provide better outcomes in controlling metastatic NSCLC in patients with high PD-L1 levels. The study includes patients with measurable non-brain lesions and no prior systemic treatment for metastatic NSCLC. During the trial, patients will be closely followed for up to approximately 36 months to measure overall survival and progression-free survival. Researchers will assess the safety and effectiveness of the treatments through regular evaluations, including monitoring for disease progression and survival status. This long-term follow-up ensures comprehensive understanding of treatment impact over time.

Researchers are evaluating the effectiveness and safety of mexiletine hydrochloride in men with spinal and bulbar muscular atrophy, a condition causing muscle weakness due to lower motor neuron lesions. This clinical trial aims to determine if mexiletine hydrochloride can improve motor function, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) score. The study is a multicenter, randomized, placebo-controlled, double-blind trial conducted in phases 2 and 3. Participants will be randomly assigned to receive either mexiletine hydrochloride or a placebo. Mexiletine hydrochloride is given orally at a dose of 300 mg daily, divided into three doses after meals, for 12 weeks. The placebo is administered in the same way and schedule. During the study, participants visit the hospital every 4 weeks for evaluations and monitoring. Throughout the trial, researchers will assess participants' ALSFRS-R scores at 4 weeks to measure motor function improvements. Participants will also undergo regular evaluations at each 4-week visit to monitor safety and treatment effects. The total duration of participation is approximately 3 months, during which adherence and any side effects will be closely observed.

Advanced airway procedures, such as tracheal intubation, are critical and high-risk events for children in intensive care units (ICUs) and emergency departments (EDs). This study evaluates the current practices for these procedures in pediatric intensive care units (PICU), cardiac ICUs (CICU), neonatal ICUs (NICU), emergency departments, and delivery rooms. It is part of a multi-center collaborative network called NEAR4KIDS, aiming to understand and benchmark airway safety practices across multiple centers. The study collects baseline data on airway management events, including tracheal intubations, laryngeal mask placements, emergency tracheostomies, and cricothyrotomies, in various pediatric care settings. It also considers failed or unplanned extubations requiring re-intubation as new intubation events. These data will be used to develop and assess quality improvement interventions to enhance patient safety and care quality. Participants are monitored throughout their hospital stay, averaging about four weeks, to track the number of tracheal intubation associated events (TIAEs). The study involves continuous data collection and comparison across centers to evaluate the impact of quality improvement efforts on airway management safety. Events occurring in operating suites are excluded from this evaluation.

Researchers are evaluating the safety and effectiveness of JNJ-90301900 (NBTXR3) combined with radiation therapy, with or without cetuximab, in elderly patients who have locally advanced head and neck squamous cell carcinoma (LA-HNSCC) and are not eligible for platinum-based chemotherapy. This Phase 3, global, open-label, randomized study focuses on treatment-naive participants aged 60 and older with this specific type of cancer. The study compares two treatment approaches: one group receives JNJ-90301900 (NBTXR3), an investigational drug made of inert hafnium oxide particles designed to enhance the effect of radiation, combined with intensity-modulated radiation therapy (IMRT) delivering 70 Gray over 35 fractions in 7 weeks, plus the option of cetuximab; the other group receives radiation therapy with or without cetuximab according to the investigator's choice. Participants receive their assigned treatments during the study period. Participants will be closely monitored through 30 months after the first randomized participant to assess progression-free survival based on independent central review. Researchers will evaluate treatment safety and effectiveness, including regular assessments of cancer progression and patient health status. The study includes detailed eligibility screening and ongoing follow-up to ensure patient well-being throughout the trial.

Researchers are investigating whether a combination of antiplatelet drugs works as well as intravenous tissue plasminogen activator (rt-PA) in treating small ischemic strokes known as lacunar strokes. This phase 4 trial aims to determine if the dual antiplatelet therapy is not inferior to the current standard rt-PA treatment and if it reduces bleeding complications compared to rt-PA. Participants will receive either a low-dose rt-PA treatment (0.6 mg/kg alteplase) or a dual antiplatelet therapy consisting of aspirin 200 mg and clopidogrel 300 mg. Treatment is given during the hyperacute phase of stroke, within 4.5 hours of symptom onset. The study compares these two approaches to assess their effectiveness and safety. During the study, participants will be monitored for neurological status three months after their stroke. Assessments may be conducted in person, by phone, or by mail. The main outcome measured is the proportion of participants achieving an excellent outcome three months post-stroke. Safety and treatment effects will be closely observed throughout the trial.

Researchers are conducting a long-term follow-up study to monitor the safety and effectiveness of gene-modified (GM) T-cell therapy in both children and adults who have previously received this treatment in Celgene or Celgene alliance partner-sponsored trials. This study focuses on participants with a history of neoplasms and aims to track outcomes for up to 15 years after the last GM T-cell infusion. No new investigational treatments will be given during this follow-up study. Participants who received at least one GM T-cell infusion in prior studies and have either ended or completed the follow-up in those parent trials will be invited to enroll. The study will observe participants across an extended period without administering additional therapies. Throughout the study, researchers will assess the incidence of delayed adverse events, the persistence of the gene-modified T cells, vector integration sites, and the occurrence of replication-competent lentiviruses for up to 15 years post-infusion. For pediatric participants, physical growth and sexual maturation will also be monitored up to 15 years or until reaching Tanner Stage 5. Additional measures include tracking disease progression and overall survival among those originally diagnosed with cancer.