Birmingham

Researchers are evaluating a new hospital incubator pad that provides stochastic vibrotactile stimulation SVS as a complementary treatment for apnea of prematurity AOP, a common condition in preterm infants where breathing stops for 20 seconds or more. This study aims to establish the safety, effectiveness, and clinical risks and benefits of this device, which could improve management of AOP beyond the current standard therapy of caffeine citrate. The study focuses on newborns born before 33 weeks gestational age and younger than 38 weeks postmenstrual age at enrollment. The study compares two groups one receiving standard therapy with caffeine citrate plus continuous SVS stimulation via the Prapela SVS incubator pad, and a control group receiving standard therapy with an inert pad that looks identical but does not vibrate. Treatment with the SVS pad continues until the infant is apnea-free for three days and less than two weeks from anticipated discharge, or until the clinician decides to stop. If apnea returns after stopping, treatment may be restarted. Follow-up surveys will be conducted by telephone at 1 and 2 years of age to assess neurological development. Participants will be monitored closely with clinical evaluations and questionnaires completed by clinicians to assess risks and benefits. The primary outcome is the change in apnea rate during 7 to 28 days of intervention, with secondary outcomes assessed at earlier time points. The study is randomized and single-masked, with safety and efficacy data gathered to support possible FDA clearance and future use of the SVS incubator pad as an adjunctive therapy to improve outcomes in preterm infants with AOP.

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with 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, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are evaluating the safety, tolerability, and early effects of 4D-710, an investigational gene therapy, in adults with cystic fibrosis CF lung disease who cannot use or tolerate existing CFTR modulator therapies. A sub-study also includes adults with advanced CF lung disease or frequent lung flare-ups who are currently on CFTR modulator therapy. This Phase 12 open-label trial aims to find appropriate dosing and assess potential benefits for these patient groups. Participants receive a single inhaled dose of 4D-710, which is a gene therapy designed to deliver a corrected version of the CFTR gene to lung cells. The study includes a dose exploration phase for those ineligible for modulator therapy, a dose expansion phase at selected doses, and a sub-study for participants on modulator therapy receiving various doses. Each participant undergoes one administration of the therapy during the trial. Throughout the study, participants are monitored for adverse events over a 60-month period. Evaluations include lung function tests, oxygen saturation measurements, and tracking of pulmonary exacerbations. Participants maintain their existing treatments if applicable, and researchers assess safety and early signs of effectiveness. The total study duration extends up to approximately nine years, including long-term observation after dosing.

Researchers are evaluating the use of psilocybin, a 5-HT2A receptor agonist, for helping adults with tobacco use disorder quit smoking. This phase 2, multi-site, double-blind, randomized clinical trial involves 66 participants across four experienced research sites. The study aims to compare psilocybin with niacin, an active placebo, both combined with cognitive behavior therapy CBT, to assess smoking cessation effectiveness and related cognitive changes over 12 months. Participants will be randomly assigned to receive either oral psilocybin or oral niacin in two sessions spaced one week apart. Psilocybin doses are 30 mg in the first session and either 30 mg or 40 mg in the second, depending on responses to a mystical experience questionnaire. Niacin doses are 150 mg in the first session and either 150 mg or 200 mg in the second, following the same dosing schedule. Both groups receive CBT alongside the medication sessions to support quitting smoking. During the study, participants will undergo assessments including cognitive control tasks and questionnaires about smoking urges at screening and shortly after a target quit date. Smoking abstinence will be biochemically confirmed and measured for up to 12 months. Safety and health status will be monitored through interviews, physical exams, ECGs, and lab tests. The trial also investigates psychological factors that may influence quitting success, with overall participation lasting about one year.

Researchers are evaluating the effectiveness of delgocitinib cream applied twice daily compared to a cream vehicle for treating adults with mild to severe lichen sclerosus LS, a skin condition affecting mostly females in the anogenital area. The study is conducted in two parts Part 1 enrolls female participants to determine the best dose, and Part 2 includes both female and male participants to further assess the chosen dose and safety in males. Participants receive different dosing regimens of delgocitinib cream or cream vehicle applied twice daily during a 12-week initial treatment period, followed by a 40-week continuation treatment period. Different groups receive varying doses or sequences of delgocitinib cream and cream vehicle to compare effects. A substudy evaluates male participants separately to assess safety and efficacy. During the trial lasting between 55 and 60 weeks, participants undergo regular assessments including clinical evaluations of LS severity using IGA-LS scores, pain and itch numerical rating scales, and quality of life indexes. Safety is monitored through adverse event tracking and laboratory tests. The main outcome measured is the number of participants achieving a specific improvement in LS severity at Week 12, with additional evaluations continuing through Week 52.

Opioid overdose deaths have reached record highs in the United States, especially among patients discharged from emergency departments ED. This research aims to evaluate a bundled intervention combining telehealth, peer support, buprenorphine treatment, and linkage to addiction programs to increase treatment uptake, reduce repeat opioid overdoses, and lower mortality in patients with opioid use disorder OUD after ED discharge. The study is supported by the HEAL Initiative and focuses on patients with recent opioid overdoses who face barriers to treatment after leaving the ED. The study includes two phases. In phase 1, 30 patients discharged from the ED will receive daily peer support via telehealth during the first week, then less frequently over 12 weeks, alongside buprenorphine prescribed by physicians. In phase 2, about 160 participants will be randomized to either the same bundled intervention or usual care, which includes ED-initiated buprenorphine and referral lists but no ongoing peer support. The intervention lasts 3 months post-ED discharge, and participants in all groups will complete follow-up surveys at 1 and 3 months. Participants will be involved in baseline assessments, receive the intervention or usual care after ED discharge, and complete self-report questionnaires through electronic surveys at 1 and 3 months. Peer supporters will remind participants to complete surveys. The study will measure treatment retention, adherence to buprenorphine, and successful linkage to addiction treatment programs at 1 and 3 months after ED discharge. These outcomes will help assess the feasibility and impact of this bundled approach to reduce opioid overdose risks and improve care continuity.

Researchers are evaluating the safety and efficacy of the study drug LY4065967 for treating diabetic peripheral neuropathic pain DPNP. This trial is part of a larger chronic pain master protocol designed to accelerate the development of new treatments for chronic pain conditions. The study focuses on adults with DPNP related to type 1 or type 2 diabetes. Participants will be randomly assigned to receive either LY4065967 or a placebo, both taken orally. The study is double-blinded, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts eight weeks, during which participants take the assigned study drug daily. Throughout the trial, participants will report their pain intensity and other symptoms at the start and after eight weeks using various scales, including the Numeric Rating Scale and Brief Pain Inventory. Researchers will also monitor sleep quality, emotional functioning, and the use of rescue medication. Safety and tolerability will be assessed, and the study concludes in July 2027.

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.