A Randomized Double-Blind Placebo-Controlled Study to Evaluate the Safety Tolerability Pharmacokinetics of AHB-137 with Single Ascending Doses and Multiple Doses in Healthy Volunteers and Initial Efficacy in Chronic Hepatitis B Patients
This phase I study is designed to evaluate the safety, tolerability, and pharmacokinetics ofAHB-137 in healthy participants and initial efficacy in CHB patients.A Safety Review Committee (SRC) will perform ongoing reviews of safety and tolerabilitybased on available study data collected throughout the study.The study will be conducted in four Parts:Part A: SAD in healthy participants (double blinded)Part B: MD in healthy participants (double blinded)Part C: MD in CHB patients (open label)Part D: MD in CHB patients (double blinded; multiple sites)
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 parallel-group double-blind placebo-controlled multicenter Phase III trial to investigate the efficacy and safety of secukinumab 300 mg and 150 mg administered subcutaneously versus placebo both in combination with a glucocorticoid taper regimen in patients with giant cell arteritis (GCA) (GCAptAIN)
The purpose of the study is to demonstrate the efficacy and safety of secukinumab 300 mg and 150 mg administered subcutaneously in adult patients with newly diagnosed or relapsing giant cell arteritis (GCA). The study will take about 2 years and during that time, patients will visit the Study Doctor about 26 times. At the study visits, the following procedures should happen: Blood tests, other study specific assessments and study treatment injection. Patients will receive on of the following treatments: Group 1: secukinumab 300 mg (2 mL PFS) s.c. at Baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4 in addition to prednisone with dosing tapered over a period up to 26 weeks. Patients have a two in three possibility of getting this treatment.Group 2: placebo to secukinumab 300 mg (2 mL PFS) s.c at Baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4 in addition to prednisone with dosing tapered over a period up to 52 weeks. Patients have a one in three possibility of getting placebo, which has no active ingredients
A RANDOMIZED PHASE II TRIAL OF ADJUVANT NIVOLUMAB WITH OR WITHOUT CABOZANTINIB IN PATIENTS WITH RESECTED MUCOSAL MELANOMA
The study is designed to help patients with different stages of mucosal melanoma, a type of skin cancer. There are three groups, or arms, in thestudy. In the first two arms, patients who had surgery to remove the cancer are registered and then randomly assigned to one of two treatmentgroups. In the first group, patients receive a combination of Nivolumab and Cabozantinib after surgery. In the second group, patients receiveNivolumab and a placebo (a harmless pill with no medicine). Before assigning the treatment, patients are tested to see if they have high or lowlevels of a protein called PD-L1. Other factors like where the cancer started, whether it has spread to nearby lymph nodes, and if the patient had radiation therapy are also considered. For patients whose cancer couldn't be completely removed or has spread to other parts of the body, they are assigned to the third arm, called the advanced arm. In this group, patients receive treatment with Nivolumab and Cabozantinib. The same factors mentioned earlier are used todetermine the treatment plan for these patients. The duration of treatment depends on the arm. In the first two arms, treatment is given for 1 year or until the cancer gets worse or the treatmentcauses serious side effects. In the advanced arm, treatment continues for 2 years or until the cancer gets worse or the treatment causes seriousside effects. Patients will be checked regularly after treatment. Every 3 months, their condition will be monitored to see if the cancer is gettingworse. After that, they will be followed up every 6 months for up to 5 years from when they joined the study or until they pass away, whicheverhappens first.
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 Trial of Cryoprobe Versus Forceps for Transbronchial Biopsy (FROSTBITE-II)
Prospective, multi-center, randomized controlled trial inpatients undergoing bronchoscopy with transbronchialbiopsy for evaluation of diffuse parenchymal lungdisease, lung transplant or pulmonary parenchymallesions
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.
A sham-controlled pilot trial of focused ultrasound modulation of the globus pallidus interna in schizophrenia
The primary objectives of this study are to examine the tolerability of pulsed low-intensity focused ultrasound (PLIFUS) and its effects on brain function measured via fMRI functional connectivity and symptom response in individuals with schizophrenia. A neuronavigated single-element piezoelectric device will be utilized to noninvasively deliver transcranial PLIFUS sonication to the right globus pallidus interna, a brain region implicated in schizophrenia. We aim to enroll N=12 participants with schizophrenia in a random order, sham-controlled crossover trial of a single session of PLIFUS counterbalanced with a single sham sonication session, one week apart. After the participant provides written informed consent, a medical and psychiatric evaluation will be performed to determine eligibility for inclusion in the study, followed by a structural MRI to guide neuro-navigation. The first intervention visit will include a 10 minute PLIFUS sonication or sham sonication, preceded and followed by fMRI and an exit medical examination. Psychiatric symptoms will be assessed immediately prior to sonication/sham, during sonication/sham and 5 minutes, 30 minutes, 60 minutes, 1 day and 7 days after sonication/sham. The second intervention visit will consist of sonication or sham preceded and followed by fMRI in addition to symptom assessments and post-sonication/sham medical evaluation. Participants will be closely monitored during and after procedures for tolerability and adverse effects, including 1 and 7 day follow-up visits. The goal of this pilot study is to establish feasibility and tolerability and to determine whether the sonication procedure produces effects on the imaging biomarker and on symptoms prior to proceeding to therapeutic trials using repeated administration. If PLIFUS effects on fMRI and symptom ratings are not detected in the first 4 completers, subsequent participants will receive 3 sessions over 5 days.
A single arm open-label multicenter phase II study of 177Lu-DOTATATE radionuclide in adults with progressive or high-risk meningioma
This single arm, open-label study will evaluate the efficacy of Lutathera (177Lu-DOTATATE) administered intravenously every 8 weeks for a total of 4 doses in patients with progressive WHO I-III or residual high-risk 68Ga-DOTATATE PET-MRI positive meningioma. 68Ga-DOTATATE MRI scans will be obtained before and 6 months after initiation of treatment .
A Single-Arm Phase 2 Study Of Daratumumab In Previously Treated Stk11/Lkb1 Mutated Non-Small Cell Lung Cancer
This is a single arm, signal finding study of daratumumab in metastatic NSCLC patients with an STK11/LKB1 mutation. Patients will have received previous standard of care treatment including chemotherapy, immunotherapy and targeted therapy. We plan to enroll a total of 14 patients. Patients will be treated with the standard subcutaneous dosing of daratumumab (weekly for 8 administrations, then every 2 weeks for 8 administrations then every 4 weeks until progression). All follow-up visits and imaging will be performed as per standard of care. This is a signal finding stud