Providence

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are evaluating a phase II, randomized, double-blind, placebo-controlled study involving 48 adults aged 18 to 70 years who have recently been diagnosed with acute HIV infection. The study aims to assess whether adding a combination of HIV-specific broadly neutralizing antibodies (bNAbs) to standard antiretroviral therapy (ART) is safe and whether this combination can delay the return of detectable HIV viral levels, reduce viral reservoirs, and improve HIV-specific immune responses compared to ART with placebo. Participants receive either the combination bNAbs or placebo along with ART at the start of the study. The bNAbs include VRC07-523LS given as a 10 mg/kg intravenous infusion over 15 to 30 minutes and PGT121.414.LS given as a 5 mg/kg intravenous infusion over 30 to 60 minutes, both administered once at entry. ART consists of daily oral tablets containing bictegravir, emtricitabine, and tenofovir alafenamide. The study includes multiple steps: initial treatment with ART and antibody or placebo infusions (Step 1), analytic treatment interruption (ATI) to monitor viral rebound (Step 2 and Step 3), and ART restart when criteria are met (Step 4). Throughout the study, participants undergo regular visits with laboratory tests to monitor HIV viral load, CD4+ T-cell counts, safety labs, and pregnancy tests when applicable. Researchers track the occurrence of significant adverse events related to the study antibodies and measure the time it takes for HIV viral levels to rebound after stopping ART. Participants must adhere to contraceptive requirements and use barrier methods to prevent HIV transmission during ATI. The total study duration includes treatment, interruption, and follow-up phases lasting up to 24 weeks or longer depending on individual progress.

Researchers are evaluating the safety and effectiveness of a treatment called RD2 Ver.02 compared to a control in managing transsphincteric and intersphincteric anal fistulas. The study focuses on complication rates at 6 months, recurrence at 12 months, and infection rates within 6 months after treatment. This clinical trial is conducted in a blinded, randomized manner to carefully compare outcomes between the two groups. Participants will be randomly assigned to one of two groups. Both groups will have blood drawn for blinding purposes, the fistula will be cleaned and the internal opening sutured closed, followed by a water leak test to ensure sealing. In the treatment group, the patient's own coagulating blood (RD2 Ver.02) will be applied into the fistula tract to help healing, while the control group will receive saline applied in the same way. The treatment is delivered using a semi-flexible cannula to apply the substances inside the fistula. During the study, participants will undergo assessments including blood draws, fistula evaluations, and imaging such as pelvic MRI before enrollment. Researchers will measure healing rates, complication rates, and infection incidence up to 6 months and recurrence at 12 months. Safety and effectiveness will be monitored throughout, with follow-up visits to track outcomes and any adverse events.

Researchers are evaluating AZD8421, a CDK2 inhibitor, alone and combined with other targeted anti-cancer drugs in female patients with ER+ HER2- advanced breast cancer and metastatic high-grade serous ovarian cancer. This Phase I/IIa study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of AZD8421. The study includes patients previously treated with CDK4/6 inhibitors or platinum-based chemotherapy, focusing on those with progressing metastatic or locoregionally recurrent disease. The study includes two main parts: AZD8421 monotherapy and combination therapy. Monotherapy evaluates AZD8421 alone to find the recommended Phase II dose in patients with advanced breast or ovarian cancer. Combination therapy tests AZD8421 with a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) and camizestrant, an oral SERD, in breast cancer patients previously treated with CDK4/6 inhibitors. Treatment safety and drug behavior are closely monitored throughout. Participants will undergo assessments for dose limiting toxicities and adverse events from treatment start through an approximately 18-month safety follow-up. Researchers will also monitor laboratory tests, vital signs, ECGs, and reasons for stopping AZD8421 due to toxicity. The study requires measurable or assessable tumor lesions and performance status evaluations, ensuring patients meet specific health criteria. Total participation duration includes treatment and extended safety monitoring.

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.

Researchers are evaluating the safety and preliminary effectiveness of SAR445877, given alone or with other anticancer treatments, in adults aged 18 and older who have advanced, hard-to-remove, or metastatic solid tumors. This Phase 1/2 study includes multiple groups and aims to find appropriate doses and understand how well the treatment works, including combinations with cetuximab, ADG126, or bevacizumab. The study involves about 542 participants, including those in a Japan-specific group, reflecting a wide range of advanced solid tumor types. The study has two main parts. Part 1 focuses on dose escalation to identify safe and effective doses of SAR445877 given either every two weeks or weekly, alone or combined with other therapies. Part 2 involves expanding and optimizing doses to assess safety and early effectiveness in various tumor types and treatment combinations. Participants receive SAR445877 and other drugs by infusion. Treatment continues until disease progression, unacceptable side effects, or other reasons for stopping treatment. Participants will undergo screening for up to 28 days before starting treatment, then receive ongoing therapy with regular monitoring. Assessments include scans and tests to measure tumor response, safety evaluations for side effects including dose-limiting toxicities, and follow-up visits after treatment ends. The study tracks outcomes during treatment cycles and for up to two years in the expansion phase, with safety follow-up lasting 30 days after the last dose. Overall, the participation duration varies depending on individual course and response.

Researchers are evaluating the safety and effectiveness of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as initial treatments for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC) whose tumors express PD-L1. This Phase III, randomized, double-blind, global study focuses on patients whose tumors meet the PD-L1 expression threshold of 1% or higher and do not have certain genetic mutations or rearrangements that would require other targeted therapies. Participants receive either rilvegostomig or pembrolizumab intravenously on the first day of each 21-day treatment cycle. Both groups also receive platinum-based chemotherapy drugs such as carboplatin or cisplatin, administered intravenously up to four cycles, along with pemetrexed given intravenously on Day 1 of each cycle. The study monitors these treatments as first-line therapy for metastatic non-squamous NSCLC. During the study, participants undergo regular assessments including imaging scans to measure tumor size and response, as well as evaluations of organ and bone marrow function. Researchers track overall survival and progression-free survival for up to approximately five years. Safety is closely monitored throughout, and patients are followed long-term to assess outcomes related to treatment effectiveness and tolerability.

Researchers are conducting a master protocol study called CAMPFIRE to efficiently carry out multiple clinical trials testing new drugs in children and young adults with cancer. This master protocol allows for adding new studies as new cancer drugs become available, focusing on the treatment of measurable or evaluable tumors in participants aged 1 to 39 years. The goal is to evaluate various drugs under a unified research plan to improve treatment options for young cancer patients. The study involves several investigational drugs administered either intravenously or orally, including Ramucirumab, Cyclophosphamide, Vinorelbine, Gemcitabine, Docetaxel, Abemaciclib, Irinotecan, and Temozolomide. Each drug is tested under specific clinical trials within the master protocol, with treatment schedules and dosing tailored to each drug. Participants receive these treatments following standard clinical procedures, with adjustments based on individual study protocols and treatment responses. Participants will be closely monitored throughout the trial, with assessments including performance status evaluations, laboratory tests to check organ and blood function, and pregnancy testing for females of childbearing potential. Researchers will track how many participants receive each treatment during the first four weeks and observe the duration of treatment benefits. Safety evaluations, adherence to contraceptive measures, and recovery from prior therapies are also part of the study monitoring. Participation duration and additional assessments depend on the specific trial and treatment plan assigned.

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Researchers are evaluating the mobile game Viral Combat to see how well it works and how acceptable it is for people aged 15 to 34 who are receiving pre-exposure prophylaxis (PrEP) care for HIV prevention in clinical settings in New England and Mississippi. The study includes interviews with healthcare workers, clinic administrators, and patients to help improve the game and make sure it fits the needs of diverse populations and clinics. This trial is a multisite randomized controlled study comparing Viral Combat to a control group playing a non-PrEP related game. Participants will receive either the Viral Combat mobile game, which is designed to support adherence to PrEP through information, motivation, and behavior techniques, along with adherence-based text messages, or a control condition involving a non-PrEP related mobile game. The study involves 200 participants divided between clinics in Jackson, Mississippi, and sites in Providence and Boston, Massachusetts. The trial includes formative evaluation interviews before the game testing and summative evaluation interviews after the trial to assess factors related to the game's implementation. During the study, participants' adherence to PrEP will be measured using biological tests for tenofovir concentration in blood samples, clinical records, and self-reports. Researchers will also look at factors such as knowledge, motivation, and self-efficacy related to the intervention. Interviews with participants and clinic staff will provide insights for future use and distribution of Viral Combat. The total participation involves the intervention period and assessment of outcomes at 24 weeks.