A Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Fazirsiranin the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease with METAVIR Stage F2 to F4 Fibrosis
This is a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of fazirsiran (TAK-999, previously called ARO-AAT) in the treatment of subjects aged 12 to 75 years (inclusive) with AATD-LD moderate to advanced fibrosis and compensated cirrhosis.The study will enroll subjects with PiZZ AATD-LD with METAVIR stage F2, F3, or F4 liver fibrosis. Approximately 126 up to 140 subjects are planned to be randomized 1:1 to receive either placebo or fazirsiran administered subcutaneously (SC). Subject randomization will be stratified according to METAVIR stage (F2 or F3 vs F4). The F4cc population will be capped at 25% of the total subjects with the remaining 75% being comprised of F2 and F3 subjects.
A RANDOMIZED DOUBLE BLIND PLACEBO-CONTROLLED STUDY OF THE EFFECTS OF STELLATE GANGLION BLOCK ON NEURAL ACTIVITY AND SYMPTOMS IN PARTICIPANTS WITH POST-TRAUMATIC STRESS DISORDER
We are doing this research study to learn more about how a Stellate Ganglion Block (SGB) procedure changes activity in the brain in subjects with Post-traumatic Stress Disorder (PTSD). PTSD is a mental health disorder that some people develop after witnessing or experiencing a traumatic event. People who have PTSD re-experience the traumatic event and feel the same fear and discomfort that they associated with the trauma long after the danger has gone.
A Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients with Primary Sclerosing Cholangitis (VISTAS)
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, single, inferentially seamless, adaptive design clinical study that will be conducted in 3 parts.The primary and secondary objectives and endpoints will be evaluated in participants with PSC who have a baseline score of =4 on the Adult Itch-Reported Outcome (ItchRO), as assessed during the single-blind placebo run-in period during the core study.
A Randomized Open-label Phase 3 Study of Adjuvant Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician s Choice in Patients with Triple Negative Breast Cancer That Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy
This is an international, multicenter, open-label, randomized, Phase 3 study inpatients with TNBC who have received neoadjuvant chemotherapy with or without checkpoint inhibitor (CPI) therapy, with a finding of invasive disease in the breast or axillary lymph nodes after surgery.Patients must have had adequate excision and surgical removal of all clinical evidence of disease in the breast and/or lymph nodes as well as radiotherapy as indicated in the eligibility criteria prior to screening.Approximately 1514 patients will be enrolled at approximately 300 sites globally.Triple negative breast cancer status must be confirmed per current American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines for humanepidermal growth factor receptor 2 (HER2) testing. Estrogen receptor (ER) and progesterone receptor (PgR) expression must be < 10%. Patients who have known ER-positive (= 10%), PgR-positive (= 10%), HER2-positive breast cancer—as defined by current ASCO/CAP guidelines, or germline breast cancer gene (BRCA) mutation—are not eligible to participate inthe study. TNBC diagnosis from postsurgical tissue sample is preferred and will be used for eligibility determination in case of discordant expression results from pretreatment diagnostic biopsy.A tumor tissue block (preferably) from diagnostic pretreatment core biopsy or at least 10-15 freshly sectioned unstained slides will be required. Tumor specimen from the surgical resection will also be mandatory (tumor tissue block preferable, or at least 20-25 freshly sectioned unstained slides). Tumor PD-L1 status will be assessed retrospectively in a central laboratory using the PD-L1 immunohistochemistry (IHC) 22C3 assay. Tumor tissues will also be analyzed retrospectively for Trop-2 levels and other potential exploratory biomarkers.Eligible patients will be randomly assigned (1:1) to one of the following 2 arms for treatment:Arm A: SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles for 8 cycles and pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cyclesArm B: TPC; TPC will be limited to one of the following treatment regimens determined prior to randomization:Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cyclesPembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles andcapecitabine 1000 mg/m2 orally twice daily on Days 1 through 14 of 21-day cycles for up to 8 cyclesNo other treatment regimen is allowed and no crossover to SG is permitted. Treatment in both arms will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.Randomized patients will be stratified according to the following factors:Prior anti–programmed cell death ligand 1 [aPD-(L)1] therapy (yes versus no)Prior anthracycline-based therapy (yes versus no)Pathologic nodal status at time of surgery (ypN0 versus ypN+)Geographic region (US versus East Asia versus Rest of World)The study will be conducted in 3 parts: screening, treatment period, and long-term follow-up.
A Randomized Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wildtype Recurrent Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy
This is a randomized, open-label, active-controlled, parallel-group, multicenter, interventional, Phase 3 study of amivantamab and FOLFIRI compared with cetuximab or bevacizumab (investigator’s choice) and FOLFIRI in participants who have recurrent, unresectable or metastatic CRC that is KRAS/NRAS and BRAF WT.Participants must have received and radiographically progressed on or after fluoropyrimidine- and oxaliplatin-based chemotherapy, with or without anti-VEGF treatment, and must not have received prior irinotecan-based chemotherapy in the metastatic setting, anti-EGFR therapy, or anti-MET therapy.The screening period will be up to 28 days prior to randomization. The treatment period will begin on Cycle 1 Day 1 and continue as 28-day cycles. Participants will receive study treatment until radiographic disease progression by BICR or other discontinuation criteria are met. Participants will then be followed for survival, subsequent anticancer treatment, and disease status. Participant safety and study conduct will be monitored throughout the study.Following the final analysis of OS, participants who continue to benefit from study treatment, as determined by the investigator, may continue to receive access to study treatment(s), either via an open-label or long-term extension rollover study or any other post-trial access program, when available and permitted by local regulations.
A Randomized Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
This is a phase 3 study testing and comparing if study medicine amivantamab (monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI (chemotherapy) is more beneficial than another medicine called cetuximab (Monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI for patients whose colorectal cancer has spread from the primary location and that the tumor has KRAS/NRAS and BRAF wild-type genes. Patients will be divided into two groups. One group will receive amivantamab together with mFOLFOX6 or FOLFIRI, and the other group will receive cetuximab and mFOLFOX6 or FOLFIRI. All participants will have special scans taken to see if the study treatment is changing their tumor size and that the cancer is not progressing. The study team will collect blood samples from all patients to see how their bodies are responding to these medicines and whether antibodies to the study medicine are formed. Genetic testing will be done on blood and tumor samples in the hope of further helping patients. All patients will be monitored for side effects and safety throughout the study.
A RANDOMIZED PHASE II TRIAL OF ADJUVANT NIVOLUMAB WITH OR WITHOUT CABOZANTINIB IN PATIENTS WITH RESECTED MUCOSAL MELANOMA
A RANDOMIZED PHASE II TRIAL OF ADJUVANT NIVOLUMAB WITH OR WITHOUT CABOZANTINIB IN PATIENTS WITH RESECTED MUCOSAL MELANOMA
A randomized phase II trial of adjuvant trastuzumab emtansine (T-DM1) followed by subcutaneous trastuzumab versus paclitaxel in combination with subcutaneous trastuzumab for Stage I HER2-positive breast cancer (ATEMPT 2.0)
This is a randomized phase II adjuvant study for women and men with Stage I HER2-positive invasive breast cancer. At least 500 eligible patients will be randomized 3:1 to trastuzumab emtansine (T-DM1), followed by subcutaneous (SC) trastuzumab (Herceptin Hylecta) (n = 375) or paclitaxel plus trastuzumab SC (TH) (n = 125). Patients may have any hormone receptor status, may be either pre- or post-menopausal, and must be systemic treatment-naïve for this cancer. HER-2 positivity will be confirmed by central testing in all patients. Patients will bestratified by Age (
A randomized phase III study of neoadjuvant chemotherapy followed by surgery versus surgery alone for patients with High Risk RetroPeritoneal Sarcoma (STRASS 2)
In this study, patients will fill out Health-Related Quality of Life (HRQoL) questionnaires when they visit the hospital for their scheduled appointments. These questionnaires will follow the EORTC guidelines. The main copies will be sent to the hospitals, and if more copies or translations are needed, they can be requested from the EORTC contact person. Clinical report forms will ask if the HRQoL questionnaires were completed, and if they weren't, the reasons will be noted. Patients will receive the questionnaires from the doctor or a study nurse before their check-ups, and they should complete them on their own in their own language during the visit. A designated person, like a research nurse, will help make sure that patients fill out the questionnaires correctly and completely. The study will check how well patients follow through with completing the questionnaires at each visit, and this will be reviewed every six months and included in reports.
A Research Study to See if Kidney Damage in People with Chronic Kidney Disease and Type 2 Diabetes Living with Overweight or Obesity Can Be Reduced by CagriSema Compared to Semaglutide Cagrilintide and Placebo
The purpose of this study to see if CagriSema can lower kidney damage in people with with chronic kidney disease (CKD), type 2 diabetes (T2D), and overweight or obesity. We will also compare the effect of CagriSema to semaglutide and cagrilintide, when they are taken alone, and to placebo. Type 2 diabetes is a disease where the blood sugar is not well controlled. This is because the bodydoes not react well to insulin and does not produce enough insulin. Having T2D can cause many different health problems, for example CKD. If untreated, CKD is likely toworsen over the years. Keeping a well-controlled blood sugar and body weight may reduce the risk ofgetting the disease or worsening of the disease. Thus, apart from keeping a well-controlled blood sugarand body weight, people with CKD also need treatment to prevent or lower the kidney damage andkeep their kidneys from getting worse. CagriSema is an investigational drug that’s a combination of two other drugs: cagrilintide andsemaglutide. Cagrilintide is an investigational medicine under development. Semaglutide is FDA-approved to treat people with type 2 diabetes and overweight. Semaglutide is a medicine similar to a hormone called glucagon-like peptide-1 (GLP-1) that is made in your body after a meal. Semaglutide makes you feel full and less hungry and helps your body to regulate its blood sugar levels. Both medicines can lower blood sugar and body weight, and they may do so more when taken together than alone.