Berlin

Researchers are evaluating whether the introduction of dedicated hospital-based HIV teams can improve HIV testing rates among patients with HIV indicator conditions across ten European countries. This real-world, multicenter, stepped-wedge cluster randomized effectiveness-implementation trial spans four years and involves hospitals in the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. The study aims to address the current gap in HIV testing and improve early diagnosis by comparing testing rates before and after the implementation of HIV teams. The intervention involves creating local HIV teams led by HIV specialists, supported by nurses and data collectors. These teams focus on auditing and providing feedback to healthcare professionals to encourage HIV testing when indicated, reducing stigma, educating staff on HIV prevention and care, and improving linkage to local prevention services. The HIV teams use electronic health records to identify patients with HIV indicator conditions and integrate their activities into routine hospital care. Participants' data are collected retrospectively from routine care and prospectively at the healthcare professional level. Researchers measure changes in HIV testing rates, new HIV diagnoses, and variations across countries and specialties. They also assess the HIV diagnosis and care cascade, healthcare professionals' knowledge and stigma levels, and implementation outcomes such as resource use and cost-effectiveness. Monitoring includes feedback loops and evaluation of barriers and facilitators to implementation, aiming to improve HIV testing and care sustainability in hospitals.

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

Researchers are conducting a phase II, multicenter, open-label trial to investigate the combination of Fruquintinib and Tislelizumab in patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) metastatic colorectal cancer who do not have active liver metastases. The study aims to evaluate the effectiveness of this combination in comparison to a control treatment for this specific group of patients. Participants will be randomly assigned to one of two treatment groups. The experimental group will receive oral Fruquintinib (5 mg daily for 21 days in each 28-day cycle) along with intravenous Tislelizumab (400 mg every 42 days). The control group will be treated with oral Trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus intravenous Bevacizumab (5 mg/kg every 14 days). Treatment continues until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging to monitor disease status and safety evaluations. Follow-up will continue for up to 18 months after the last patient enrolls or until death, withdrawal, or loss to follow-up. The main outcome measure is the efficacy of Fruquintinib combined with Tislelizumab in this patient population over a 54-month period.

Researchers are evaluating remibrutinib (LOU064) in adolescents aged 12 to under 18 years who have chronic spontaneous urticaria (CSU) that is not well controlled by H1-antihistamines. This Phase 3 trial aims to assess the effectiveness, how the drug is processed in the body, and safety of remibrutinib compared to a placebo. The study also intends to gather long-term data on how well remibrutinib works and its safety over several years after treatment ends. The trial includes three periods. First, the core period is a 24-week double-blind phase where about two-thirds of participants receive remibrutinib and one-third receive placebo, with about 10 site visits over approximately 32 weeks. Next is an optional open-label extension lasting from one to three years, where participants who completed the core period may receive remibrutinib or enter an observational treatment-free phase depending on their symptoms. Participants may cycle through treatment and observational periods up to six times. Finally, an optional long-term treatment-free follow-up can last up to three years with one site visit and up to four phone calls. During the study, participants undergo assessments including changes in urticaria activity scores (UAS7), itching severity (ISS7), and hive severity (HSS7) measured from baseline to 12 weeks. Regular visits monitor safety, symptoms, and drug effects. The study tracks these measures to understand remibrutinib's impact on CSU symptoms and overall safety profile during and after treatment, with total participation potentially lasting several years.

This research aims to evaluate the effects of litifilimab (BIIB059), a monoclonal antibody, in adults with active subacute or chronic cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE). Participants have active skin symptoms of CLE that have not improved with antimalarial therapy or had difficulties continuing that treatment. The study focuses on reducing skin disease activity using several scores including CLA-IGA-R and CLASI, while also assessing safety, immune response, and quality of life. Participants will be randomly assigned to receive either litifilimab or a placebo injection under the skin every four weeks during a 24-week double-blind period where neither participants nor researchers know which treatment is given. After this, all participants will receive litifilimab injections every four weeks for an additional 28 weeks. Those who complete the treatment may join a long-term extension study or enter a follow-up safety period lasting up to 24 weeks. Total participation may last up to 80 weeks. Throughout the study, researchers will monitor skin disease activity using the CLA-IGA-R erythema score and the CLASI-A activity score to see how many participants improve. They will also assess safety, tolerability, immune system effects, and participants' quality of life using questionnaires. These evaluations occur regularly during both treatment periods and follow-up to understand the impact of litifilimab on CLE symptoms and overall health.

Researchers are evaluating the safety, tolerability, and levels of the study drug SYX-5219 in healthy volunteers and people with moderate to severe atopic dermatitis (AD). This multi-part, Phase 1, first-in-human study includes participants aged 18 to 65 years. The study aims to understand how SYX-5219 behaves in the body and to assess its safety in different dosing scenarios, including single and multiple doses as well as food effects. The study is divided into three parts. Part 1 involves single ascending doses (SAD) and a food effect evaluation in up to 48 healthy volunteers, who receive oral capsules of SYX-5219 or placebo. Part 2 tests multiple ascending doses (MAD) in up to 24 healthy volunteers with multiple oral doses given over a treatment period. Part 3 enrolls up to 45 participants with confirmed active AD to receive SYX-5219 or placebo daily for up to 42 days. This part is conducted at multiple global sites. Participants will undergo safety and exploratory efficacy assessments during treatment and follow-up periods. Researchers will monitor adverse events from the date of consent through various time points depending on the study part, including up to 10 days after dosing in Part 1 and up to 56 days in Part 3. Assessments include laboratory tests, vital signs, ECGs, and clinical evaluations to gather information on safety, tolerability, and drug levels in blood and urine throughout the study duration.

Researchers are evaluating the safety and effectiveness of rilzabrutinib compared to placebo in adults with active Immunoglobulin G4 Related Disease (IgG4-RD). This Phase 3, randomized, double-blind study aims to measure the time until the first IgG4-RD clinical disease flare during a 52-week treatment period. Additional goals include assessing disease control, flare-free rates, use of glucocorticoid rescue, and monitoring safety through adverse events, laboratory tests, and electrocardiograms. Participants will be randomly assigned to receive either oral rilzabrutinib tablets or placebo for 52 weeks. Glucocorticoids may be used as rescue medication if needed. The study includes a screening period lasting 4 to 6 weeks before treatment begins, followed by the 52-week double-blind treatment phase, and a 2-week follow-up after treatment. An optional open-label extension lasting up to 108 weeks is also available for participants. During the study, participants will attend 16 visits for assessments, which may include clinical evaluations, imaging tests such as CT, MRI, PET, or ultrasound to monitor disease activity, and laboratory tests. Researchers will track time to disease flare and collect data on flare-free rates, safety parameters, and medication use. Participants' vaccination status and contraceptive use will be monitored according to local guidelines, and overall study participation could last up to 60 weeks or longer if joining the extension phase.

Researchers are studying metastatic colorectal cancer (mCRC) patients to evaluate a new treatment called arfolitixorin combined with fluorouracil, oxaliplatin, and bevacizumab. This clinical trial aims to find the safest and most effective dose of arfolitixorin, which is a form of folate that may work better than the current standard leucovorin by being active immediately without needing conversion in the body. The study is divided into two parts: a Phase 1b dose-finding phase and a Phase 2 randomized dose optimization phase. In the first part, up to five doses of arfolitixorin will be tested to identify the highest well-tolerated dose and the best administration duration. In Phase 2, patients will be randomly assigned to one of two doses (the maximum tolerated dose or a lower dose) while continuing treatment with fluorouracil, oxaliplatin, and bevacizumab every two weeks via intravenous infusion. Treatment will continue as long as patients benefit and tolerate it. The study will take place at several sites in Germany. Participants will undergo baseline assessments and have imaging scans (CT or MRI) at specified intervals to monitor tumor response and disease progression. Health will be checked through physical exams and lab tests of blood and urine. After stopping treatment, follow-ups will occur every 90 days for up to 24 months or until enough survival events are recorded. The study will measure safety, tolerability, and tumor response to evaluate the potential benefits and risks of arfolitixorin in this patient population.

Researchers are studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.