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Researchers are evaluating the safety, tolerability, and effectiveness of CYB003, a Deuterated Psilocin Analog, compared to a placebo when added to current antidepressant treatment in adults with moderate to severe Major Depressive Disorder (MDD). This Phase III trial focuses on participants aged 18 to 85 years who have had inadequate response to a stable antidepressant dose, aiming to better understand how CYB003 might improve depressive symptoms. Participants receive oral doses of CYB003 or matching placebo along with manualized psychological support provided by trained facilitators. The treatment period includes multiple dosing sessions with monitoring and assessments throughout. Placebo is used as a comparator to evaluate the combined safety and efficacy of CYB003 in this population. During the study, participants undergo evaluations using the Montgomery-Åsberg Depression Rating Scale (MADRS) at several time points, including screening, baseline, and multiple days up to the end of treatment at Day 42. Researchers monitor symptoms, side effects, and overall safety. Participants provide informed consent and are assessed regularly to track changes in depression severity and any adverse events over the course of the study.

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 investigating the safety and effects of 4D-150 gene therapy in adults aged 50 and older with neovascular (wet) age-related macular degeneration (AMD) who are already receiving anti-VEGF treatment and have shown a clinical response. This Phase 1/2 trial includes dose-escalation and randomized, controlled, masked expansion phases, aiming to evaluate 4D-150 administered by intravitreal injection in one eye, with additional substudies assessing dosing in the second eye and vector shedding. Participants will receive a one-time dose of 4D-150 by injection into the study eye, followed by monthly assessments for 24 months to monitor safety and effectiveness. Those who receive 4D-150 will then enter a long-term follow-up period up to 5 years to assess ongoing safety and the duration of treatment effects. Substudies include one for contralateral eye dosing and another to characterize vector shedding, with participants monitored regularly for safety through one year and continuing long-term follow-up through year 5. Throughout the study, participants will undergo tests of visual and retinal function and structure, with assessments performed monthly initially and safety monitored for up to five years. Researchers will track treatment-emergent adverse events, serious adverse events, and any significant changes in safety parameters. Participants must comply with study procedures and visits, and males receiving 4D-150 will be advised to use barrier methods during intercourse for six months to prevent fluid transmission.

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 investigating why some men with Benign Prostatic Hyperplasia (BPH) do not respond to the common treatment drug Finasteride. The study focuses on identifying molecular and epigenetic changes, particularly in the SRD5A2 gene, that may predict resistance to this therapy. The goal is to use noninvasive methods like prostate MRI and gene expression analysis to help predict which patients will benefit from Finasteride and which may need alternative treatments. Men eligible for this study will start Finasteride treatment and be monitored every 6 months for changes in urinary symptoms. Prostate MRIs will be performed at the beginning and after 3 years to assess size and inflammation changes. Additionally, prostate tissue samples will be tested for gene expression and methylation patterns of SRD5A2, along with hormone levels measured in blood samples. Participants will have regular clinic visits to evaluate urinary symptom scores and treatment response over 12 months. Researchers will measure improvements in lower urinary tract symptoms and track prostate changes through imaging and laboratory tests. The study aims to clarify Finasteride responsiveness and improve personalized treatment options for men suffering from BPH.

Researchers are evaluating the use of two different creams for treating low-risk skin cancers, specifically superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). 5-Fluorouracil cream is FDA approved and commonly used for these conditions with a typical treatment period of 4 weeks. This study aims to compare this standard treatment with a compounded cream containing a 1:1 ratio of 5-fluorouracil and calcipotriene, which has been effective in clearing pre-skin cancers and preventing new skin cancers from developing. Participants will be randomly assigned to apply either the standard 5-fluorouracil cream twice daily for 28 days or the combination cream twice daily for 7 to 14 days, with evaluation at 7 days to determine if treatment should continue up to 14 days. The creams are applied to the lesion plus 0.5 cm of surrounding skin. This pilot randomized single-blinded trial will assess how well each treatment clears the cancer lesions. Participants will be monitored for lesion clearance at 3 months and then followed for up to 3 years with visits at 6 months and additional follow-ups consistent with standard care. If lesions remain or are unclear, biopsies will be performed and standard care provided. The study will track cancer lesion clearance and treatment response over time to compare the two regimens’ effectiveness.

Researchers are investigating the effects of XYOSTED as a testosterone replacement therapy in adolescent males aged 12 to under 18 years who have primary or secondary hypogonadism. This Phase 3/4, open-label, multicenter study aims to evaluate how well XYOSTED supports puberty continuation or induction, as well as its dosage, safety, and testosterone level outcomes. Participants have a confirmed deficiency or absence of endogenous testosterone and will be assessed for pubertal development and hormone levels before starting treatment. Participants will receive XYOSTED injections with dosages tailored to their weight and targeted Tanner Stage of puberty. Dose adjustments will be made regularly based on serum total testosterone levels measured at specific intervals after dosing, with evaluations approximately every three months to reach desired testosterone levels. After completing the 52-week primary study, participants may join a 24-month long-term safety extension with clinic visits every six months for ongoing clinical, laboratory, and pharmacokinetic assessments. During the study, participants will undergo thorough clinical examinations including pubertal staging, multiple testosterone measurements, and monitoring for safety and pharmacokinetics throughout treatment and extension periods. Researchers will track changes in testosterone levels from enrollment through week 53 and monitor overall safety. The study includes detailed follow-up and dose management to support pubertal development and assess long-term effects of XYOSTED therapy in this population.

Researchers are evaluating whether a new imaging probe called [64Cu]FBP8, used with combined cardiac PET and MRI scans, can detect blood clots inside the heart in people with cardiac amyloidosis and atrial fibrillation or atrial flutter. This pilot Phase 3 study involves twenty adults with transthyretin or light chain cardiac amyloidosis. The main goal is to see if [64Cu]FBP8 PET/MRI can identify intracardiac thrombi in over 90% of cases confirmed by a transesophageal echocardiogram (TEE). Secondary analyses will explore links between these clots, left atrial function, and amyloid buildup in the heart's left ventricle. Participants will receive an injection of the [64Cu]FBP8 tracer followed by simultaneous cardiac PET and MRI imaging to detect thrombi. The study compares these imaging results with TEE findings, which serve as the reference standard. Both retrospective participants who had a TEE within 14 days and prospective participants scheduled for an upcoming TEE will be included. This design helps ensure accurate comparison between the new imaging method and the current standard. During the study, participants will undergo PET/MRI scans after tracer injection, and researchers will collect imaging data to assess thrombus presence. Safety considerations include screening for implants, recent major cardiac events, and ability to lie still during imaging. The main outcome measure is detecting intracardiac thrombus within one day after the imaging procedure. Overall participation includes informed consent, imaging procedures, and follow-up assessments to evaluate the probe's accuracy and relationships with heart function and amyloid burden.