Pamplona

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the safety and potential benefits of VHB937 in people aged 50 to 85 years with early Alzheimer's disease, including those diagnosed with Mild Cognitive Impairment due to Alzheimer's or mild Alzheimer's disease. This Phase II, multicenter, randomized, double-blind, placebo-controlled study aims to assess how VHB937 affects memory, thinking abilities, daily activities, and brain changes, while also studying how the body processes and responds to the treatment. The study includes an initial 72-week double-blind phase followed by an extension period. Participants will receive either VHB937 solution for infusion or a placebo solution through infusion during the 72-week double-blind phase. The study compares these two groups to evaluate the effects and safety of VHB937 in early Alzheimer's disease. After the double-blind phase, participants may continue in an extension period for further observation. Treatment involves regular infusions under controlled conditions throughout the study. During the study, participants and their study partners will attend visits for assessments including memory and cognitive tests, evaluations of daily functioning, brain imaging, and biomarker analysis from cerebrospinal fluid or PET scans. Researchers will monitor safety, record any side effects, and track changes using the Clinical Dementia Rating scale (CDR) over 72 weeks. The study requires a reliable partner to accompany participants to visits, and overall participation includes monitoring during treatment and the extension phase to thoroughly assess VHB937's effects and safety.

Researchers are evaluating CPV-104, a new medicine designed to regulate the complement system, which can be overactive in rare kidney diseases like C3 glomerulopathy (C3G). This is the first time CPV-104 is being tested in people. The study includes both healthy adults and adult patients with C3G to assess safety, tolerability, how the body processes the medicine, and immune system reactions. The study is a phase 1, first-in-human trial with two parts: Part 1 involves healthy volunteers receiving a single dose, while Part 2 involves C3G patients receiving multiple doses. The trial has two parts: Part 1 (Single Ascending Dose with healthy volunteers) is double-blind, randomized, and placebo-controlled, where healthy adults receive a single intravenous (IV) dose of CPV-104 or placebo. Part 2 (Multiple Ascending Dose with C3G patients) is open-label and single-arm, with patients receiving four weekly IV doses of CPV-104. Safety data is regularly reviewed by a Safety Review Committee before advancing to higher doses or new groups. All doses are given by healthcare professionals. Participants will undergo close monitoring throughout the study, including checks for side effects, blood and urine tests, ECGs, vital signs, and blood samples to measure drug levels and antibodies. For C3G patients, kidney function will also be observed, although the main focus is safety rather than effectiveness. The study tracks serious and severe drug reactions up to Day 29 for healthy volunteers and Day 50 for C3G patients to ensure safety. The total study length varies by part and cohort.

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 creating a European registry and sample sharing network called EUREKA to collect all new cases of systemic AL amyloidosis from referral centers across Europe. This project aims to use advanced molecular technologies and big data analysis, including artificial intelligence, to better understand the disease mechanisms. The study focuses on improving early diagnosis, guiding treatment decisions, describing the disease course in patients, and detecting minimal residual disease after therapy. The registry will gather patient data along with biological samples for detailed molecular analysis of disease-causing light chains and plasma cells. A dedicated site will support the consortium with data analysis using advanced computational methods. This approach intends to refine technologies that detect residual disease with high sensitivity in patients who have achieved complete hematologic response to treatment. Participants will be followed over time at participating centers, with data collected on their clinical outcomes. The main outcome measure is mortality at 24 months from diagnosis. Patients will provide informed consent, and their disease progression and treatment responses will be monitored to understand the natural history of AL amyloidosis in the current era of effective therapies.

Researchers are evaluating VVD-130037, a new investigational drug, in people with advanced solid tumors. This Phase 1 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of VVD-130037 alone and combined with chemotherapy drugs docetaxel or paclitaxel, or with the immunotherapy drug pembrolizumab. The study focuses on participants whose cancers have progressed despite previous standard treatments and includes specific groups such as those with squamous non-small cell lung cancer or head and neck squamous cell carcinoma. The study consists of two parts: a dose escalation phase where participants receive VVD-130037 alone or in combination with docetaxel, paclitaxel, or pembrolizumab to determine safe dosage and observe dose-limiting toxicities. Cycle lengths are 21 days for single agent and docetaxel/pembrolizumab combinations and 28 days for the paclitaxel combination. The dose expansion phase involves further evaluation of safety, adverse events, serious adverse events, and laboratory abnormalities over up to approximately four years. Participants will undergo evaluations including tumor measurements based on RECIST criteria, performance status checks, and organ function tests. Safety is closely monitored during the early dose-limiting toxicity periods and throughout the study. Researchers will collect data on side effects, lab results, and overall clinical status to understand how the treatments affect participants over time. The study includes regular follow-up visits and assessments to ensure participant safety and gather comprehensive treatment information.

Researchers are evaluating AZD8421, a CDK2 inhibitor, alone and combined with other targeted anti-cancer drugs in female patients with ER+ HER2- advanced breast cancer and metastatic high-grade serous ovarian cancer. This Phase I/IIa study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of AZD8421. The study includes patients previously treated with CDK4/6 inhibitors or platinum-based chemotherapy, focusing on those with progressing metastatic or locoregionally recurrent disease. The study includes two main parts: AZD8421 monotherapy and combination therapy. Monotherapy evaluates AZD8421 alone to find the recommended Phase II dose in patients with advanced breast or ovarian cancer. Combination therapy tests AZD8421 with a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) and camizestrant, an oral SERD, in breast cancer patients previously treated with CDK4/6 inhibitors. Treatment safety and drug behavior are closely monitored throughout. Participants will undergo assessments for dose limiting toxicities and adverse events from treatment start through an approximately 18-month safety follow-up. Researchers will also monitor laboratory tests, vital signs, ECGs, and reasons for stopping AZD8421 due to toxicity. The study requires measurable or assessable tumor lesions and performance status evaluations, ensuring patients meet specific health criteria. Total participation duration includes treatment and extended safety monitoring.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of IMP1734, a PARP1 selective inhibitor, in participants with advanced solid tumors. The study aims to assess preliminary efficacy and find the best dosing for future clinical development. This first-in-human trial is conducted in two parts, focusing on patients with recurrent, advanced, or metastatic solid tumors including metastatic prostate, ovarian, breast, and other solid tumors with specific genetic mutations. The trial has two main phases: Part 1 involves dose escalation of IMP1734 as a monotherapy to determine the maximum tolerated or achievable dose in solid tumors. Part 2 focuses on dose optimization to select the optimal dose for further clinical use. Treatment involves oral administration of IMP1734, with dose escalation steps and combination dose escalations in specific cancers like metastatic prostate cancer, ovarian, and breast cancer. Participants will undergo regular assessments to monitor safety through adverse event tracking, pharmacokinetic and pharmacodynamic evaluations, and tumor response measurements using criteria like RECIST1.1, CA125, or PSA. The study includes monitoring for serious adverse events from consent until 30 plus 7 days after the last dose. Dose-limiting toxicities are assessed during the first treatment cycle. Participants are expected to have adequate organ function, a life expectancy of at least 12 weeks, and will be followed closely during the trial to evaluate the drug's safety and potential anti-tumor activity.

Researchers are evaluating the safety and effectiveness of pulsed field ablation (PFA) therapy for treating persistent atrial fibrillation (PersAF) that does not respond to medication. The study compares PFA targeting pulmonary veins plus extra-PV sources identified by electrographic flow (EGF) mapping against PFA targeting pulmonary veins plus the left atrial posterior wall (PVI + PWA). The goal is to establish safety and to show that the new method is not less effective than the current approach in patients with symptomatic, drug-refractory PersAF. Participants will receive treatment using several devices, including the FARAPOINT Pulsed Field Ablation System, the OptiMap System for electrogram analysis, and the FARAWAVE NAV Catheter combined with the Opal HDx Mapping System for detailed heart mapping. All subjects will undergo electroanatomical mapping of the entire left atrium, followed by pulsed field ablation of the pulmonary veins, with additional ablation of either EGF-identified sources or the posterior wall, depending on the assigned treatment group. During the study, participants will be monitored for safety outcomes at 60 days and effectiveness outcomes at 365 days. They will receive a LUX-Dx insertable cardiac monitor to track heart rhythm continuously. Researchers will collect clinical data, imaging, and follow-up assessments to evaluate treatment impact and safety. The study includes ongoing follow-up visits to ensure thorough monitoring of heart function and study outcomes over one year.

The purpose of this study is to assess the long-term safety and tolerability after an intravitreal injection (a shot of medicine into the eye) of JNJ-81201887 administered in parent clinical studies.