Guimaraes

Researchers are evaluating different weekly doses of Alpha1-Proteinase Inhibitor Alpha1-PI administered under the skin compared to the standard doses given through an intravenous IV infusion in adults with Alpha-1 Antitrypsin Deficiency AATD. This Phase 3 study aims to understand how the body processes these doses and to assess their safety and tolerability. Participants will be randomly assigned to treatment groups, and both participants and study doctors will know which treatment is given. The study involves two treatment arms. One group receives 8 weeks of IV treatment with 60 mgkgweek of Liquid Alpha1-PI followed by 8 weeks of subcutaneous SC treatment with 90 mgkgweek of Alpha-1 15. The other group receives 8 weeks of IV treatment with 120 mgkgweek of Liquid Alpha1-PI followed by 8 weeks of SC treatment with 180 mgkgweek of Alpha-1 15. These treatments are given weekly, and the study compares the effects of these doses over a total of 16 weeks. Participants will attend regular visits for monitoring and assessments during both the IV and SC treatment periods. Researchers will measure how much Alpha1-PI remains in the body over the weekly dosing interval, along with safety and tolerability. Blood tests, lung function tests, and other evaluations will be conducted throughout the study. The total participation duration is about 16 weeks, during which safety and effectiveness data will be collected and analyzed.

Researchers are evaluating the safety and effectiveness of KarXT combined with KarX-EC in adults aged 55 to 90 who experience agitation linked to Alzheimers Disease. This phase 3 trial aims to understand how these treatments impact agitation symptoms in this population. The study is sponsored by Bristol-Myers Squibb and uses rigorous methods to compare the investigational drugs against a placebo. Participants will receive either the combination of XanomelineTrospium Chloride capsules KarXT KarX-EC or a placebo, with doses given on specified days. The study is randomized, double-blind, and placebo-controlled, ensuring objective assessment of treatment effects over a 14-week period. The trial includes a parallel group design where participants are assigned to either the experimental treatment group or placebo group. During the study, participants will be assessed for changes in agitation using the Cohen-Mansfield Agitation Inventory and other related scales at week 14. Researchers will monitor safety through adverse event reports, clinical labs, vital signs, ECGs, and specific rating scales up to week 18. Caregivers will assist by attending visits and reporting on participant status. Total participation involves regular visits and assessments over the course of the trial.

Researchers are evaluating the effectiveness, safety, and tolerability of oral icotrokinra in treating adults and adolescents with moderately to severely active ulcerative colitis UC, a chronic condition where the large intestine lining becomes inflamed and develops ulcers. This Phase 3 clinical trial aims to compare icotrokinra with a placebo to better understand its impact on UC symptoms and remission rates. Participants will be divided into study groups receiving either icotrokinra or a placebo orally each day starting from Week 0 of the induction phase. After 12 weeks, responses will be assessed and participants who respond to icotrokinra or placebo enter a maintenance phase lasting up to Week 40. Adolescents receive open-label icotrokinra throughout the study, with an option for a long-term extension after completing the maintenance phase. During the trial, participants will undergo regular evaluations including clinical response, endoscopic assessments, and symptom monitoring at key points such as Weeks 12 and 40. Researchers will track remission rates, symptom improvements, quality of life, and safety outcomes. The study involves both double-blind and open-label phases and continues until January 2032, with close monitoring to understand how participants respond over time.

Researchers are evaluating the clinical efficacy, safety, and tolerability of XEN1101 as an additional treatment for people with focal-onset seizures in a Phase 3 randomized, double-blind, placebo-controlled study. This trial aims to compare two doses of XEN1101 with a placebo to see how well the medication can reduce seizure frequency in patients who continue their current antiseizure medications. The study involves adults diagnosed with focal epilepsy who have tried at least two antiseizure medicines without achieving seizure freedom. About 360 participants will be randomly assigned to receive either 25 mg or 15 mg of XEN1101 or a placebo once daily with an evening meal. The study includes up to 9.5 weeks of baseline monitoring to track seizure frequency followed by 12 weeks of blinded treatment. Participants maintaining the study drug can then join an open-label extension to continue treatment or enter an 8-week follow-up after treatment ends. Throughout the study, participants will keep accurate seizure diaries and continue their stable antiseizure medications. Researchers will measure the median percentage change in seizure frequency from baseline through the 12-week treatment period, along with secondary outcomes like the proportion of participants with at least a 50 reduction in seizures and patient-reported improvement. Safety will be monitored from screening until 56 days after the last dose. Overall, participants are involved for the baseline, treatment, and follow-up phases lasting several months.

Researchers are evaluating the antitumor activity of amivantamab combined with lazertinib or with chemotherapy in participants who have common EGFR-mutated locally advanced or metastatic non-small cell lung cancer NSCLC. This Phase 2b open-label study aims to understand how well these combinations work as first-line or second-line treatments for this type of lung cancer. Participants will be assigned to one of two groups one group will receive amivantamab combined with lazertinib orally in 28-day cycles, and the other group will receive amivantamab combined with platinum-based chemotherapy carboplatin and pemetrexed given by intravenous infusion in 21-day cycles. Treatment will continue until disease progression, withdrawal, death, or investigator decision to stop treatment. During the study, participants will undergo regular assessments including monitoring for progression-free survival up to 4 years and 6 months. Additional evaluations include tracking dose changes, adverse events, overall survival, response rates, and time to treatment discontinuation. Safety and clinical outcomes will be closely observed throughout the treatment period and follow-up.

Researchers are evaluating camizestrant, an oral selective estrogen receptor degrader, compared to standard endocrine therapy in patients with early-stage ER-positive, HER2-negative breast cancer. This Phase III open-label study focuses on individuals at intermediate or high risk for disease recurrence who have completed locoregional therapy and at least 2 years, up to 5 years, of standard adjuvant endocrine therapy. The goal is to assess if camizestrant improves invasive breast cancer-free survival and other related outcomes. Participants are randomly assigned to receive either camizestrant or continue with standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors such as exemestane, letrozole, anastrozole, or tamoxifen. Treatment duration for both groups is planned for 60 months 5 years. The study allows prior use of CDK46 inhibitors and excludes patients with specific medical conditions or prior use of similar investigational agents. During the study, patients will be regularly monitored for invasive breast cancer-free survival, invasive disease-free survival, distant relapse-free survival, overall survival, and safety measures, including adverse events and changes in laboratory and vital signs. Quality of life assessments related to symptoms like arthralgia, hot flushes, and vaginal dryness will also be conducted. Follow-up for participants will continue for up to 10 years from the last patients randomization.

Researchers are evaluating Risvutatug rezetecan Ris-Rez, a new medicine targeting specific proteins B7-H3 on cancer cells to reduce the growth and spread of relapsed small cell lung cancer SCLC. This Phase 3 study compares Ris-Rez to the standard treatment, topotecan, to see how well Ris-Rez shrinks or eliminates tumors and whether it helps participants live longer. The study also monitors safety and side effects of both treatments to understand their tolerability. Participants will be randomly assigned to receive either Ris-Rez or topotecan. Ris-Rez is a biological treatment given to target the cancer cells, while topotecan is a drug used as the active comparator. The study involves multiple assessments over time, including treatment response and disease progression, lasting up to approximately 139 weeks for some measures. During the study, participants will undergo regular evaluations including imaging scans to assess tumor response, laboratory tests to monitor organ function and side effects, ECGs to check heart function, and assessments of physical activity levels using ECOG performance status. Researchers will also measure overall survival, progression-free survival, adverse events, and participant experiences with the treatments. The total participation duration lasts up to about 113 weeks for overall survival and up to 139 weeks for other secondary outcomes.

Researchers are evaluating how well icotrokinra works and how safe it is for people with moderately to severely active Crohns disease, a condition that causes long-term inflammation in the intestines. This study is a Phase 2b3 trial that aims to understand both the effectiveness and safety of icotrokinra in treating this condition. Participants will receive icotrokinra or a matching placebo orally every day during the induction period lasting up to 12 weeks. Those who respond to the treatment at Week 12 may continue with different dosing options of icotrokinra or placebo during a maintenance phase up to Week 40. Following this, eligible participants can join a long-term extension study to further monitor treatment effects. During the study, participants will undergo evaluations of their clinical response, remission, and endoscopic response at Weeks 12 and 40 using established disease activity scores. Researchers will monitor safety by tracking adverse events up to 4 weeks after the last dose. The study includes regular assessments through endoscopy, patient-reported outcomes, and laboratory tests to measure how the disease and treatment effects progress.

Researchers are evaluating the safety and effectiveness of Ifinatamab Deruxtecan I-DXd compared with treatments chosen by physicians for adults with relapsed extensive-stage small cell lung cancer SCLC. This Phase 3 randomized study aims to see if I-DXd can improve objective response rates and prolong overall survival compared to other standard treatments. The study also examines other factors such as patient-reported outcomes, immunogenicity, B7-H3 protein expression, and pharmacokinetics of I-DXd. Participants are randomly assigned to one of two groups. One group receives I-DXd at a dose of 12 mgkg intravenously on Day 1 of each 21-day cycle until unacceptable side effects, disease progression, or withdrawal. The other group receives one of three treatmentstopotecan, lurbinectedin, or amrubicinbased on the doctors choice and local guidelines, continuing until treatment criteria for stopping are met. No placebo is used, and the study is open-label. During the study, participants will have tumor assessments and survival monitored up to about five years. Evaluations include measuring tumor response by independent review and investigators, progression-free survival, duration of response, quality of life questionnaires, safety monitoring for adverse events, and tests of drug levels in the blood. Participants will be followed for disease progression, treatment effects, and survival throughout the study period, which may last several years.

Researchers are evaluating zolbetuximab combined with pembrolizumab and chemotherapy for adults with stomach or gastroesophageal junction GEJ cancer that is locally advanced, unresectable, or metastatic. This study focuses on cancers that do not have the HER2 protein but do express Claudin 18.2 and PD-L1 proteins. The goal is to find out how long people live after receiving zolbetuximab with pembrolizumab and chemotherapy compared to a placebo with the same treatments. Participants will receive treatment in 6-week cycles. The study treatment includes zolbetuximab or a placebo given by infusion every 2 or 3 weeks, combined with pembrolizumab infusions every 3 or 6 weeks. Chemotherapy options include CAPOX capecitabine tablets twice daily and oxaliplatin infusion or mFOLFOX6 infusions of oxaliplatin, folinic acid, and 5-fluorouracil. After several cycles, participants may receive parts of the chemotherapy alone. Treatment continues until the cancer worsens, side effects prevent continuation, or another cancer treatment is needed. Pembrolizumab may be given for up to 2 years. During the study, participants will visit the clinic for treatment and health checks, including scans to monitor cancer changes. Researchers will watch for medical problems related to zolbetuximab and other treatments. Tumor samples may be collected if treatment stops because of cancer progression. After stopping treatment, participants will have continued health checks and scans every 9 to 12 weeks, plus telephone check-ins every 3 months. The frequency of visits depends on each persons health and treatment status.