Zutphen

Researchers are evaluating the safety and effectiveness of brenipatide at different dose levels compared with placebo in adults with uncontrolled moderate to severe asthma. This Phase 2 study aims to better understand how brenipatide may affect asthma symptoms and exacerbations over one year of treatment. Participants in this study are adults aged 18 to 75 years with a history of asthma and recent severe exacerbations. Participants will be randomly assigned to receive either one of two doses of brenipatide or a placebo, all administered by subcutaneous injection. The treatment period lasts 52 weeks, during which participants receive their assigned injections and are monitored regularly. The study includes a screening period before treatment and a follow-up period after treatment to assess ongoing safety and effects. During the study, participants will attend visits to complete questionnaires, lung function tests such as forced expiratory volume in one second FEV1, and assessments of asthma control and medication use. Researchers will monitor asthma exacerbation rates, rescue medication use, and the presence of anti-drug antibodies. The total study duration including screening, treatment, and follow-up is approximately 65 weeks.

Researchers are evaluating AZD0292, a bispecific IgG1k monoclonal antibody, for preventing exacerbations in bronchiectasis patients who are chronically colonized with Pseudomonas aeruginosa PsA. This Phase IIb study compares two dosage regimens of AZD0292 administered intravenously with placebo in participants aged 12 years and older. The study mainly focuses on non-cystic fibrosis bronchiectasis patients with frequent pulmonary exacerbations due to chronic PsA colonization, which negatively affects lung function, quality of life, and survival. Additionally, patients with cystic fibrosis bronchiectasis colonized with PsA are included as an exploratory group. Participants will receive either high-dose or low-dose AZD0292 starting on Day 1 via IV infusion, or placebo administered similarly. Subsequent doses will follow a schedule of assessments. This randomized, double-blind, placebo-controlled, parallel study aims to assess the efficacy, safety, and pharmacokinetics of AZD0292 over a variable follow-up period ranging from a minimum of 28 weeks up to 52 weeks. The trial also includes monitoring for adverse events and immune responses to the treatment. During the study, participants will undergo evaluations including lung function tests, quality of life questionnaires, and monitoring of exacerbation rates. Blood samples will be collected to measure drug concentration and antibody development. Safety assessments will continue through the treatment period and for up to 24 weeks after the last dose. The primary outcome is the annualized rate of exacerbations over the follow-up time, and secondary measures include severe exacerbation rates, time to first exacerbation, and changes in quality of life scores. Total participation spans from screening through the treatment and follow-up phases.

Researchers are evaluating the effects of Dato-DXd combined with osimertinib or Dato-DXd alone compared to platinum-based doublet chemotherapy in people with EGFR-mutated locally advanced or metastatic non-small cell lung cancer NSCLC whose disease progressed after prior osimertinib treatment. This Phase III, open-label, randomized study aims to compare progression-free survival among these treatments to better understand options for this condition. Participants are randomly assigned to one of three groups Dato-DXd plus osimertinib, Dato-DXd alone, or platinum-based doublet chemotherapy. Dato-DXd is given as an intravenous infusion every 3 weeks, osimertinib is taken orally daily, and chemotherapy involves pemetrexed combined with carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance pemetrexed. Treatments continue until disease progression, unacceptable side effects, or other reasons to stop. Throughout the study, participants undergo regular assessments including radiological scans to monitor tumor response using RECIST v1.1 criteria, safety evaluations, and health status measurements. After stopping treatment, an end-of-treatment visit occurs within 35 days, followed by safety follow-up 28 days after the last dose. The study primarily measures progression-free survival over up to 2.5 years, with additional outcomes including overall survival, response rates, quality of life, and pharmacokinetics monitored for up to 3.5 years.

Researchers are evaluating the efficacy and safety of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease COPD who are receiving inhaled maintenance therapy. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study focuses on adults aged 40 to 80 years who have experienced multiple COPD exacerbations in the year prior to enrollment. The trial aims to assess tezepelumabs impact compared to placebo on COPD exacerbations and lung function. Participants will receive monthly subcutaneous injections of one of two doses of tezepelumab or a matching placebo. Treatment duration ranges from a minimum of 52 weeks to a maximum of 76 weeks. Following the treatment period, participants will undergo a 12-week off-treatment safety follow-up to monitor any lasting effects. Throughout the study, participants will be regularly assessed for COPD exacerbations, lung function changes measured by forced expiratory volume FEV1, and quality of life using questionnaires such as the St. Georges Respiratory Questionnaire and COPD Assessment Test. Blood samples will be collected to measure drug levels and immune responses. Safety and efficacy will be closely monitored, with total participation lasting up to approximately 88 weeks including follow-up.

Researchers are studying patients with stage II primary invasive cutaneous melanoma to compare the effects of two different surgical excision margins 1cm versus 2cm. The goal is to determine if narrower margins are as safe as wider margins in preventing melanoma recurrence and if they can improve patients quality of life. This trial also looks at the impact of these excision sizes on health services and society. Participants will be randomly assigned to receive either a 1cm or 2cm wide local excision margin around the primary melanoma lesion. Both groups will undergo sentinel lymph node biopsy and may have reconstruction surgery if needed. The surgery must be done within 120 days of diagnosis and within 28 days of randomization. During the study, participants will be followed for up to 60 months to measure disease-free survival as the primary outcome. Additional assessments include local recurrence, distant disease-free survival, melanoma-specific and overall survival, quality of life questionnaires, neuropathic pain evaluations, adverse event monitoring, and health economic analysis. Follow-up questionnaires and safety checks will occur at multiple time points up to 24 months after surgery, with longer-term monitoring continuing up to 120 months.

Researchers are studying bronchiectasis in adults and adolescents aged 12 to under 18 who produce sputum and have experienced flare-ups. The trial aims to evaluate whether the medicine BI 1291583 can help reduce these flare-ups compared to a placebo. Participants are randomly assigned to receive either BI 1291583 or a placebo in a phase III, double-blind study. Participants take one tablet of either BI 1291583 or placebo once daily for up to 1 year and 6 months. The study includes two groups one receiving the active medication and the other receiving placebo tablets that look identical but contain no medicine. The study period lasts up to 1 year and 8 months, during which participants attend up to 10 site visits and receive about 13 phone calls. During the study, participants regularly record their bronchiectasis symptoms in a smartphone diary. Study doctors monitor participants health, note any flare-ups, and check for unwanted effects. Researchers compare the number of flare-ups between the two groups as the primary measure. Secondary measures include time to first flare-up, quality of life changes, lung function changes, and rates of severe flare-ups.

Researchers are evaluating the follow-up care for patients with stage III non-small cell lung cancer NSCLC. The study compares overall survival over three years between patients who receive follow-up surveillance using 18F-Fluorodeoxyglucose Positron Emission TomographyComputerized Tomography 18F FDG PETCT and those who undergo conventional CT scan surveillance. This is to determine if the addition of 18F FDG PETCT scans improves early detection of cancer recurrence and impacts survival and quality of life. Participants are randomly assigned to two groups the intervention group receives usual care plus additional whole-body 18F FDG PETCT scans at 6, 12, 18, 24, and 36 months during follow-up, while the control group receives regular follow-up with physical exams and CT scans at least every six months for two years, then yearly until three years. After the 36-month period, all patients continue usual care with CT scans. The PETCT scans follow a specific low-dose protocol covering the skull to the mid-femoral region. During the study, participants complete quality of life questionnaires at each visit and may optionally participate in interviews and blood sample collection to assess secondary outcomes. Researchers measure overall survival at three years, recurrence detection, event-free survival, cost-effectiveness, and health-related quality of life. The study involves monitoring medical resource use and patient experiences, with results analyzed using survival curves and statistical tests over the three-year follow-up period.