Birmingham

Researchers are evaluating a new hospital incubator pad that uses stochastic vibrotactile stimulation (SVS) to help treat apnea of prematurity (AOP), a condition where preterm infants stop breathing for 20 seconds or longer or have shorter pauses with low oxygen levels. AOP is common in babies born before 34 weeks and causes significant health challenges and costs. The study aims to establish the safety, effectiveness, and risk/benefit of this novel device as a complementary treatment to the current standard therapy, caffeine citrate, which has been the only approved treatment for over 20 years but does not fully prevent apnea events. The trial involves two groups: the intervention group receives standard care with caffeine citrate plus continuous SVS stimulation using the Prapela SVS incubator pad, while the control group receives standard care with caffeine citrate and an inert, non-vibrating pad to mask caregivers. Treatment continues until the infant has been apnea-free for 3 days and less than 2 weeks from expected discharge or until the clinician decides to stop. After treatment ends, patients are observed for 24 hours, and treatment can be restarted if apnea returns. Follow-up surveys on neurological development will be conducted by phone at 1 and 2 years of age. During the study, researchers will monitor the number of apnea events over 7 to 28 days of intervention, aiming for a 30% or greater reduction. Clinicians will complete questionnaires assessing the risk and benefit of the device at the end of each experimental period. The study will collect safety and efficacy data to support FDA marketing clearance and to improve clinical outcomes for preterm infants with AOP.

Researchers are investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the safety, effectiveness, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

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 evaluating 4D-710, an investigational gene therapy, in adults with cystic fibrosis (CF) lung disease who cannot use or tolerate CFTR modulator therapy. This Phase 1/2, multicenter, open-label trial also includes a sub-study assessing 4D-710 in adults with advanced CF lung disease or frequent lung flare-ups despite using CFTR modulators. The study aims to assess the safety, tolerability, and early effectiveness of this gene therapy in these populations. The trial involves a single dose of 4D-710, which is a gene therapy using a specialized virus to deliver a modified CFTR gene. Participants receive this treatment once, and those in the sub-study must be on a stable CFTR modulator regimen for at least 60 days before screening and continue it during a 24-month observation period. The study monitors participants with CF lung disease ranging from moderate to advanced stages. During the study, participants undergo regular evaluations including lung function tests, oxygen level checks, and monitoring for adverse effects. Researchers track the occurrence and severity of any side effects over a 60-month period. The study also includes assessments of lung health, medication adherence, and clinical status to understand the therapy's impact and safety over time.

Researchers are evaluating the use of psilocybin, a 5-HT2A receptor agonist, to help people quit smoking in this multi-site, double-blind, randomized clinical trial. This study focuses on adults with tobacco use disorder who have struggled to quit smoking despite multiple previous attempts. The trial aims to compare the effects of psilocybin against niacin as a placebo, with both groups also receiving cognitive behavioral therapy (CBT) to support smoking cessation. Previous studies have shown promising results for psilocybin, but this study will provide a more rigorous test across diverse participant groups and multiple research sites. Participants will be randomly assigned to receive two sessions of either oral psilocybin (30 mg initially and then 30 or 40 mg one week later) or oral niacin (150 mg initially and then 150 or 200 mg one week later). Both groups will receive CBT alongside the drug sessions. Niacin is used as an active placebo to mimic some physical effects without the psychedelic impact. The treatment sessions are one week apart, and the study involves 66 participants across four research sites experienced in psilocybin research. Throughout the 12-month study, participants will be closely monitored for smoking cessation using biochemical tests to confirm abstinence from smoking. Researchers will assess the primary outcome of biologically-confirmed 7-day point-prevalence abstinence at 12 months. Additional cognitive and psychological evaluations will explore how psilocybin may influence smoking behavior and withdrawal anticipation. Participant health will be carefully monitored through interviews, physical exams, ECGs, and lab tests to ensure safety during the trial.

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, how the body processes, and effects on body weight of the investigational drug CRB-913 in participants with obesity. This Phase 1b study includes two parts: Part 1 focuses on healthy adults to measure drug levels in the blood after a single dose, while Part 2 involves obese participants to assess safety and weight effects using different doses compared to placebo. Part 2 is blinded so that participants, doctors, and the sponsor do not know who receives the drug or placebo. In Part 1, healthy adults receive a single dose of CRB-913 tablets to study how much of the drug enters the bloodstream and how long it stays. In Part 2, obese participants take one of three doses of CRB-913 or placebo once daily for 12 weeks. After treatment ends, participants are monitored for 28 days. The study includes a randomized, double-blind, placebo-controlled design for Part 2. Participants will attend study visits for drug administration, safety assessments, and blood tests to measure drug levels and effects on body weight. Researchers will monitor for side effects and adverse events from the first dose through 28 days after final dosing. The total participation time includes the 12-week treatment period plus the 28-day follow-up phase to evaluate safety and drug behavior in the body.

Opioid overdose deaths have reached record highs in the United States, especially among patients after emergency department (ED) discharge. This research aims to test a bundled intervention designed to increase treatment uptake, reduce repeat opioid overdoses, and prevent overdose deaths in patients with opioid use disorder (OUD) who have experienced nonfatal opioid overdoses. The study includes patients discharged from the ED with recent opioid overdoses and focuses on improving care with a combination of telehealth, peer support, medication, and community treatment linkage. The intervention includes peer support specialists contacting patients daily in the first week after ED discharge, then twice a week in the second week, and weekly for 12 weeks via telehealth. Physicians will prescribe buprenorphine doses ranging from 4mg to 24mg daily. Peers will also help motivate and connect participants to community-based addiction treatment programs for ongoing care. The study has two phases: an initial phase enrolling 30 patients to assess feasibility and acceptability, followed by a randomized phase with 160 patients split between the bundled intervention group and a usual care group that receives ED-initiated buprenorphine and a list of community programs without additional peer support. Participants will be monitored for treatment retention, adherence to buprenorphine, and successful linkage to addiction treatment programs at 1 month and 3 months after ED discharge. The study will also track repeat opioid overdoses and emergency visits. Assessments include regular peer contact, medication monitoring, and engagement with community services. The total participation time spans at least 3 months post-ED discharge, with outcomes focusing on improving treatment uptake and reducing opioid overdose risks.

Researchers are evaluating the safety and effectiveness of the drug LY4065967 for treating diabetic peripheral neuropathic pain (DPNP). This study is part of a larger chronic pain master protocol aimed at speeding up the development of new treatments for chronic pain. Participants have diabetic peripheral neuropathy mainly affecting their lower limbs and have had this condition for at least six months. The study compares oral LY4065967 to a placebo, with participants randomly assigned to either group. The trial is a Phase 2, randomized, placebo-controlled clinical trial. Treatments are given by mouth, and participants continue their usual diabetes care with stable treatment for at least 90 days before screening. During the study, researchers monitor changes in average pain intensity using a numeric rating scale from baseline to week 8. Participants undergo assessments including blood sugar control (HbA1c), body mass index measurement, and safety monitoring for heart and vitamin B12 status. The trial is designed for adults aged 18 years and older and includes close observation to ensure participant safety throughout the study period.

Researchers are studying whether combining calderasib, a targeted therapy for the KRAS G12C mutation, with subcutaneous pembrolizumab can treat non-small cell lung cancer (NSCLC). The study aims to determine if people receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a phase 3, randomized, open-label, multicenter clinical trial focusing on participants with advanced or metastatic nonsquamous NSCLC carrying the KRAS G12C mutation. Participants will receive one of two treatment combinations. One group will take calderasib orally along with subcutaneous pembrolizumab and berahyaluronidase alfa injections. The other group will receive subcutaneous pembrolizumab combined with chemotherapy drugs pemetrexed and a platinum-based drug, either carboplatin or cisplatin, administered by intravenous infusion. These treatments are given as first-line therapy, and the study evaluates their safety and effectiveness. During the study, researchers will monitor participants for progression-free survival, especially focusing on those with at least 1% PD-L1 tumor proportion score, for up to approximately 48 months. Participants will undergo regular assessments to track cancer progression and response to treatment. Safety and efficacy data will be collected throughout the study to understand how well the treatments work and their side effects over time.