A Multi-phase Dose-Escalation followed by an Open-label Randomized Crossover Study of Oral ASTX030 (Cedazuridine and Azacitidine Given in Combination) Versus Subcutaneous Azacitidine in Subjects with Myelodysplastic Syndromes (MDS) Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML)
Study ASTX030-01 is being conducted in subjects with myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MPN) including chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who are candidates to receive treatment with single agent azacitidine based on local country approvals and/or local institutional standard practice.Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3.• Phase 1 is an open-label Dose Escalation Stage (Stage A) followed by a Dose Expansion Stage (Stage B) of oral ASTX030 (cedazuridine in combination with azacitidine). Multiple doses/formulations will be evaluated. New formulations will generally be investigated in Phase 1 Stage A. Approximately 54 (Stage A) and 24-64 (Stage B) subjects will be treated in Phase 1. As of Amendment 1, an assessment of food effect (12 subjects) on the PK of ASTX030 was implemented for Phase 1 Stage B and is described below and in Section 5.3.1.As of Amendment 2, each additional dose level/formulation selected by the DSRC forevaluation in Phase 1 Stage B will be evaluated in approximately 12-24 additional subjects or as determined by the DSRC (ie, if emerging data indicates that this dose level/formulation does not achieve parity with SC azacitidine, fewer subjects may be evaluated).• Phase 2 is a randomized open-label crossover study comparing oral ASTX030 to SCazacitidine administered using the once daily × 7 days dosing schedule for each 28-day cycle as detailed in Section 1.3.1. It is expected that up to approximately 60 subjects will be treated at the RP2D depending on the number of doses/formulations tested in Phase 2.• Phase 3 is a randomized open-label crossover study comparing oral ASTX030 FDC tablet(s) to SC azacitidine administered using the once daily × 7 days dosing schedule for each 28-day cycle as detailed in Section 1.3.1. Depending on the intrapatient variability observed during Phase 2, it is expected that between approximately 75 and 115 subjects will be randomized in Phase 3.This study is designed to assess the safety and tolerability, pharmacokinetics, and clinical activity of ASTX030 and identify an oral dose combination of ASTX030 that yields azacitidine systemic exposure that approximates parity to that of SC azacitidine alone (based on total cycle azacitidine AUC0-24).
A Multi-Phase Study Examining Hospital to Home Transitions for Children with Medical Complexity
The overarching objective of this study is to make it easier for parents of children with medical complexity (CMC) to take care of their children after discharge home from the hospital and reduce the chance of post-hospitalization morbidity (meaning bad outcomes such as readmissions) after discharge. CMC, or those with multiple chronic conditions, progressive conditions, or technology dependence, are at high risk for post-hospitalization morbidity. This study will take place in 3 phases at 2 sites: Bellevue Hospital Center (BHC) and Hassenfeld Children’s Hospital (HCH). We will recruit parents of CMC with a prior or current admission at these two sites, as well as pediatricians who care for these children in the inpatient setting for the following 3 aims: - In Aim 1, we will interview parents of CMC and pediatricians to understand their views on what makes it challenging, and what can make it easier, for parents to understand and follow the instructions they get from the hospital about how to take care of their CMC after leaving the hospital. We will also ask pediatricians what may make it difficult to provide relevant education to families. We hypothesize that we will identify several contributing factors.- In Aim 2, we will design a tool to make it easier for parents to understand and follow the discharge instructions for their CMC. We will use structure of existing tool, findings from Aim 1, and extensive interviews and testing of the tool with parents and pediatricians as we design the new tool. We hypothesize that we will successfully design a tool that will be usable by both parents and pediatricians.- In Aim 3, we will use a randomized controlled trial (RCT) to study the impact of the tool on parent comprehension and adherence (or how well they can follow) their child's discharge instructions, as well as its impact on post-discharge morbidity (such as readmissions and emergency department visits). Parents will be randomized to either receive usual hospital care and instructions or the intervention/tool (in addition to the usual care and instructions). We will also ask parents who receive the intervention about its usability. We hypothesize that, compared to subjects who receive usual care, subjects in the intervention group will have higher comprehension and adherence, and their children will have lower post discharge morbidity. Parents will find the intervention to be usable.
A Multicenter Open-Label Study of RMC-6236 in Patients with Advanced Solid Tumors Harboring Specific Mutations in RAS
A Multicenter Open-Label Study of RMC-6236 inPatients with Advanced Solid Tumors Harboring Specific Mutations in RAS
A Multicenter Randomized Double-blind 2-Part Phase 2 Study to Evaluate the Efficacy and Safety of GS-1427 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
The purpose of this study is to learn more about the study drug, GS-1427. This will include: Testing if 3 different doses of GS-1427 work to treat moderate to severe Ulcerative Colitis (UC) Testing if GS-1427 is safe for people with UC Testing how the body processes and responds to GS-1427
A Multicenter Randomized Double-Blind Placebo-Controlled Non-inferiority Crossover Study Evaluating the Safety and Immunogenicity of the Herpes Zoster Subunit Vaccine in Patients with Systemic Lupus Erythematosus
This randomized, double-blind, placebo-controlled, non-inferiority crossover study will evaluate the HZ/su vaccine in SLE patients in order to evaluate safety and immunogenicity in patients with variable baseline clinical activities, ages and immunosuppressant exposures. We hypothesize that HZ/su administration will be non-inferior to placebo with respect to the risk of moderate or severe SLE flare(s) occurring within 24 weeks of receiving the first dose of the assigned treatment. In addition, we hypothesize that immunogenicity of the vaccine in SLE patients will be at least 50% of levels observed in healthy subjects from prior large clinical trials.
A Multicenter Randomized Double-blind Placebo-controlled Parallel-group Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants with Moderately to Severely Active Systemic Lupus Erythematosus
The purpose of this study is to assess if a drug called dapirolizumab pegol (DZP), used in addition to standard systemic lupus erythematosus (SLE) medication, can improve disease symptoms over a period of 48 weeks. We also want to see if DZP is safe for people with SLE.
A multicenter randomized double-blind risankizumab-controlled parallel-group study to evaluate the efficacy and safety of bimekizumab in adult study participants with active psoriatic arthritis
The purpose of this research study is to evaluate the efficacy (how well something works) and safety of bimekizumab in study participants with active psoriatic arthritis (PsA) in comparison to risankizumab.
A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and PerSiStence with Inflammatory Bowel DiSease Therapy ASSIST Study
The proposed study is a multicenter, randomized, controlled, clinical trial to be conducted over 12 months. Participants in the intervention arm will verify medication adherence using the Tappt web-based system. Additionally, they will complete a two-item assessment of symptoms monthly. Participants randomized to the control group will receive standard care. All participants are required to complete questionnaires at baseline, 12 weeks, 26 weeks, and 52 weeks.
A PHASE 0/I STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF XRD-0394 IN COMBINATION WITH RADIATION THERAPY IN PATIENTS WITH HIGH GRADE GLIOMAS
This is an open-label, dose-finding study of XRD-0394 in subjects with newly diagnosed and recurrent high grade gliomas receiving radiation therapy, with and without concurrent temozolomide based on O6-Methylguanine-DNA methyltransferase (MGMT) status for patients with newly diagnosed high grade gliomas.
A Phase 1 Clinical Trial of CA-4948 in Combination with Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma
This phase I trial tests the safety, side effects, and best dose of emavusertib (CA-4948) in combination with gemcitabine and nab-paclitaxel in treating patients with pancreatic ductal adenocarcinoma that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). CA-4948 is in a class of medications called kinase inhibitors. It works by blocking the action of abnormal proteins called interleukin-1 receptor-associated kinase 4 (IRAK4) and FMS-like tyrosine kinase 3 (FLT3) that signal cells to multiply. This may help keep cancer cells from growing. The usual approach for patients with pancreatic ductal adenocarcinoma is treatment with chemotherapy drugs gemcitabine and nab-paclitaxel. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Giving CA-4948 in combination with gemcitabine and nab-paclitaxel may shrink or stabilize metastatic or unresectable pancreatic ductal adenocarcinoma.