Los Angeles

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 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 (Z)-endoxifen as a potential treatment for premenopausal women with estrogen receptor-positive (ER+) and HER2-negative breast cancer. This phase 2 open-label study includes two parts: a pharmacokinetic (PK) phase to understand how the body processes the drug and a treatment phase to assess the drug's effects on tumor growth. The study aims to see if (Z)-endoxifen can slow or stop tumor growth by measuring changes in a biomarker called Ki-67. Participants are premenopausal women who meet specific cancer and health criteria. Participants in the PK part will take (Z)-endoxifen capsules daily at varying doses (20 mg, 40 mg, or 80 mg). Some will also receive a monthly injection of goserelin, a drug that temporarily stops estrogen production in the ovaries. The treatment cohort will receive both (Z)-endoxifen and goserelin. Tumor tissue samples will be collected by breast biopsy after about 4 weeks to assess the Ki-67 biomarker. Participants showing tumor response may continue treatment for up to 24 weeks or until they undergo surgery. Throughout the study, participants will have blood draws to measure drug levels and tumor markers, breast biopsies, imaging scans, and safety assessments. The main outcomes include measuring (Z)-endoxifen levels after 4 weeks, the rate of Ki-67 reduction, and tumor response after 24 weeks. Study participation lasts up to 6 months, including treatment, surgery, and a follow-up visit one month after surgery.

The imaging analysis will consist in obtaining quantitative measurements of lesion uptake on the pre- and post-LuPSMA RLT (lesion and whole-body SUVmax, SUVmean and tumor volume) at each time point on all PET/CT scans. PET metrics at the lesion- and whole-body level will be compared among different PET radiopharmaceuticals at the same time point, and changes over time will be assessed. All patients will be followed-up at our institution and clinical outcome will be correlated to the imaging analysis assessment.

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 the biodistribution of a radioactive agent called 99mTc-PSMA-I&S in men with prostate cancer, including those with recurrent disease. This exploratory early phase 1 study focuses on patients undergoing pelvic lymph node dissection and aims to validate findings using histopathology when possible. The study also explores how well the agent accumulates in tumor lesions and determines the best timing for radio-guided surgery after administration. Participants receive the 99mTc-PSMA-I&S agent through an intravenous injection. The first five patients undergo multiple SPECT/CT scans at various time points ranging from 3 to 46 hours after the injection, followed by a second dose before their surgery. Subsequent patients receive one dose before surgery. This technique may help surgeons detect prostate cancer spread to lymph nodes using a gamma probe during surgery. During the study, doctors will monitor the distribution of the radioactive agent in normal and cancerous tissues by measuring uptake values at different times. Participants undergo imaging scans, surgical procedures, and tissue analysis when available. The study assesses how the agent's uptake correlates with prostate-specific membrane antigen expression and aims to identify the optimal time point for surgery guidance. Safety and study compliance are also monitored throughout the participation period.

Researchers are studying a new treatment combination for adults with advanced breast cancer that is estrogen receptor positive, HER2 negative, and GRPR positive. The trial aims to find the recommended dose of the drug [177Lu]Lu-NeoB when given with ribociclib and fulvestrant to participants who have experienced early relapse after endocrine therapy or whose disease has progressed after endocrine therapy combined with a CDK4/6 inhibitor. This Phase 1 study includes a dose escalation part and a backfill part to assess safety, tolerability, and preliminary effectiveness. Participants will receive [177Lu]Lu-NeoB once every 28-day cycle for six cycles, ribociclib daily on days 1 to 21 of each cycle, and fulvestrant on specific days beginning at cycle 1. Pre- or perimenopausal women and men will also receive goserelin. The trial includes imaging with the radioactive agent [68Ga]Ga-NeoB at screening, possibly at cycle 2 day 15, and again 4 to 8 weeks after the last dose of [177Lu]Lu-NeoB to help locate cancer lesions. During the study, participants visit the clinic regularly for treatment, safety checks, and tumor assessments. Safety follow-up continues for 8 weeks after treatment ends, with extended monitoring every 12 to 24 weeks for up to 5 years to track side effects, adverse events, and treatment interruptions. Researchers will closely observe any dose-limiting toxicities and evaluate overall safety and effectiveness throughout the study period.

Researchers are conducting an open-label, multi-center, non-randomized pivotal Phase 3 study to evaluate the effectiveness and safety of PET imaging using [18F]PI-2620 for detecting tau protein buildup in people with Alzheimer's disease and control subjects. The study compares PET imaging results during life with brain tissue analysis obtained after death through autopsy, aiming to improve diagnosis of tau-related brain changes. Participants will receive an intravenous injection of the radioligand [18F]PI-2620 at a dose of 185 MBq 20%. The PET imaging will be performed to visualize tau deposits in the brain. This study focuses on assessing the diagnostic accuracy of this imaging method by comparing it to post-mortem histopathology findings. Throughout the study, participants will undergo PET scans and assessments to determine the presence and extent of tau pathology. The primary outcome measure is the ability of visual assessment of [18F]PI-2620 PET images to correctly distinguish tau neurofibrillary pathology associated with Alzheimer's disease, confirmed at autopsy within about one year. Safety and tolerability during imaging procedures will also be monitored, with a total participation period depending on the timing of brain autopsy after death.

Researchers are assessing the safety and effects of Ritlecitinib, a study medicine, for treating hidradenitis suppurativa (HS), a condition causing long-lasting, painful red skin lumps. This phase 2 study focuses on adults with moderate to severe HS who have not responded well to or cannot tolerate antibiotics. The goal is to compare experiences and outcomes between those receiving Ritlecitinib and those receiving a placebo. Participants will be randomly assigned to take either Ritlecitinib or a placebo pill once daily at home. The treatment involves an initial loading dose of Ritlecitinib for 8 weeks, followed by an 8-week maintenance dose, totaling 16 weeks of treatment. The placebo group will receive a matching pill with no active medicine. Over approximately 24 weeks, including screening and follow-up, participants will attend around 10 clinic visits for health evaluations, including physical exams, blood and urine tests, vital signs, chest X-rays, ECGs, hearing tests, and questionnaires. They will also track their medication intake and HS symptoms daily using an electronic diary on a mobile phone. The study will measure how many patients achieve at least a 50% improvement in HS symptoms by week 16 to evaluate treatment response and safety.