Ann Arbor

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.

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 studying patients with endogenous Cushing syndrome to understand how often adrenal insufficiency occurs when treated with osilodrostat combined with glucocorticoid replacement therapy. They are also assessing new steroid biomarkers to monitor if osilodrostat dosing is appropriate, along with evaluating the safety, durability, and clinical improvement during treatment. This study follows a block-and-replace approach to manage hormone levels. The study includes two phases. In Phase 1 (titration), participants start with a low dose of osilodrostat and then add methylprednisolone replacement doses. Osilodrostat dosing is increased as needed to reach target cortisol levels, with frequent check-ins and lab tests every 4 to 12 weeks. Once cortisol goals are met, participants move to Phase 2 (maintenance), where they continue their doses and are followed for 48 weeks with periodic hormone tests to monitor treatment effects. Participants provide informed consent and undergo regular monitoring including blood and urine tests to measure cortisol and steroid profiles. Study staff maintain close contact during the titration phase to watch for signs of adrenal insufficiency. Throughout the maintenance phase, participants have hormone levels checked every 3 to 6 months or as needed. The main outcome measured is the percentage of participants experiencing adrenal insufficiency during the titration phase, lasting about 24 weeks.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are investigating ways to prevent cytomegalovirus (CMV) infection in children and adolescents who have received a kidney transplant and weigh less than 40 kilograms. This Phase 1 study aims to understand how the drug letermovir behaves in the body over time and to evaluate its safety and tolerability in this young population. Participants receive letermovir orally, either as tablets or pellets, or through a gastrostomy or nasogastric tube if pellets are used. The treatment is given once daily for seven consecutive days. This study is open-label and single-arm, meaning all participants receive the same treatment, and the study monitors them closely throughout this period. During the study, participants will have blood samples collected before the first dose and at several points up to 24 hours after dosing on Day 7 to measure how the drug is processed by the body. Researchers will also monitor kidney function stability, CMV DNA levels, and any side effects to assess safety. The study focuses on children and adolescents younger than 18 years and weighing between 2.5 and less than 40 kilograms, with a total participation time covering at least seven days of treatment and associated assessments.

Researchers are evaluating the effectiveness, safety, and tolerability of subcutaneous ianalumab in adults with diffuse cutaneous systemic sclerosis. This Phase 2 study compares ianalumab with a placebo in participants diagnosed according to established classification criteria, focusing on those with active disease and specific autoantibodies. The goal is to better understand ianalumab's impact on this condition over a long treatment period. The study includes several phases: up to 6 weeks for screening, followed by a 52-week initial treatment period where participants receive either ianalumab or placebo by subcutaneous injection. After this, there is a second 52-week open-label treatment period where all participants receive ianalumab. Finally, a post-treatment follow-up period lasts at least 20 weeks and can extend up to 2 years after the last dose. Participants will undergo various assessments throughout the study, including evaluations of their skin condition using the rCRISS25 response at week 52. Safety and tolerability will also be closely monitored. The study involves regular visits for clinical evaluations, laboratory tests, and monitoring of disease activity and antibody status, with the total participation potentially lasting over two years including follow-up.

Researchers are evaluating a new community health worker-led program called Strengthening COnnections to Overcome Pain (SCOOP) that aims to help older adults living in rural areas manage chronic pain and reduce loneliness. The study focuses on whether participating in SCOOP decreases pain interference with daily activities and loneliness, and it also measures how engaged participants are with the program. The trial includes adults aged 60 years and older who experience chronic musculoskeletal pain and feelings of loneliness. Participants in the SCOOP group will watch brief weekly videos over 7 weeks that teach pain management and social connection strategies. They will also have weekly coaching sessions with a community health worker who will support them in setting behavior goals related to managing pain and improving social connections. Participants will be screened for unmet social needs and connected to appropriate resources during these sessions. During the study, participants will complete two telephone interviews about their health, mental health, and functioning—one at the start of the study and another 2 months later. Researchers will track engagement by counting the number of sessions completed within 8 weeks from the start. The total study involvement includes the intervention period and follow-up assessments to understand the program's impact on pain, loneliness, and participant engagement.

Researchers are evaluating the safety and effectiveness of a dietary supplement called resistant potato starch in reducing musculoskeletal symptoms in people with stage 0-III breast cancer or those at high risk of breast cancer. These individuals are planning to receive treatment with aromatase inhibitors, drugs commonly used to treat or prevent breast cancer. Musculoskeletal symptoms such as joint pain or stiffness often occur with aromatase inhibitor use, and this study explores whether resistant potato starch, which may promote beneficial gut bacteria, can help reduce these symptoms. Participants will take resistant potato starch by mouth during their aromatase inhibitor therapy, which they plan to receive for at least 24 weeks. The study allows concurrent treatments including gonadotropin-releasing hormone antagonist therapy, anti-osteoclast therapy, anti-HER2 therapy, ribociclib, and PARP inhibitors. The focus is on adherence to the resistant potato starch dosing over up to 24 weeks. During the study, participants will be monitored for how well they follow the resistant potato starch dosing schedule and any musculoskeletal symptoms they experience. Researchers will measure the proportion of participants who take at least 70% of the supplement doses as planned. Study involvement includes signing informed consent and regular assessments related to joint pain and treatment tolerance, with a total participation period of at least 24 weeks.

Researchers are evaluating the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome, a condition marked by reduced levels of the Nav1.1 protein due to mutations in the SCN1A gene. Zorevunersen is an investigational antisense oligonucleotide designed to increase the expression of the sodium channel Nav1.1 protein by boosting the production of its messenger RNA. This Phase 3, multicenter, randomized, double-blind, sham-controlled study aims to assess the potential of zorevunersen for disease modification by measuring changes in major motor seizure frequency and other health outcomes. The study has two treatment periods. In Treatment Period 1, participants assigned to zorevunersen receive the drug by intrathecal administration on Day 1, Day 57, Day 169, and Day 281 with doses of 70 mg initially and then 45 mg later. The sham group undergoes a procedure mimicking drug administration without receiving the drug. In Treatment Period 2, those initially on zorevunersen receive 45 mg doses on Day 393, Day 477, and Day 589. Participants initially in the sham group are then given zorevunersen doses of 70 mg on Day 393 and Day 477, and 45 mg on Day 589. Participants will be closely monitored throughout the study with a primary focus on seizure changes measured at Week 28. Secondary assessments include behavior, cognition, clinical status, and quality of life. The study includes an initial 8-week baseline period and a 6-week observation period to confirm seizure frequency and stability of other treatments. Patients may continue to an open-label extension study to receive zorevunersen if eligible. The study involves children aged 2 to under 18 years and tracks safety and tolerability alongside efficacy outcomes.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of IMP1734, a PARP1 selective inhibitor, in participants with advanced solid tumors. The study aims to assess preliminary efficacy and find the best dosing for future clinical development. This first-in-human trial is conducted in two parts, focusing on patients with recurrent, advanced, or metastatic solid tumors including metastatic prostate, ovarian, breast, and other solid tumors with specific genetic mutations. The trial has two main phases: Part 1 involves dose escalation of IMP1734 as a monotherapy to determine the maximum tolerated or achievable dose in solid tumors. Part 2 focuses on dose optimization to select the optimal dose for further clinical use. Treatment involves oral administration of IMP1734, with dose escalation steps and combination dose escalations in specific cancers like metastatic prostate cancer, ovarian, and breast cancer. Participants will undergo regular assessments to monitor safety through adverse event tracking, pharmacokinetic and pharmacodynamic evaluations, and tumor response measurements using criteria like RECIST1.1, CA125, or PSA. The study includes monitoring for serious adverse events from consent until 30 plus 7 days after the last dose. Dose-limiting toxicities are assessed during the first treatment cycle. Participants are expected to have adequate organ function, a life expectancy of at least 12 weeks, and will be followed closely during the trial to evaluate the drug's safety and potential anti-tumor activity.