Contemporary clinical trials最新文献

{"title":"Nurse AMIE randomized controlled trial to address symptom management among rural advanced Cancer patients: Addressing malignancies in everyday life","authors":"Kathryn H. Schmitz ,&nbsp;Stephen Baker ,&nbsp;Samantha J. Werts-Pelter ,&nbsp;Shawn Doerksen ,&nbsp;Charity G. Patterson ,&nbsp;Mohammed Ahmed ,&nbsp;Ray Scalise ,&nbsp;Alex Vincent ,&nbsp;Caitlyn Desroches ,&nbsp;Michele Sobolewski ,&nbsp;Rebecca Celebre ,&nbsp;Sara Garrett ,&nbsp;Nicole Stout ,&nbsp;William A. Calo ,&nbsp;Shannon Fisher ,&nbsp;Erica Schleicher ,&nbsp;Brett Gordon ,&nbsp;Praveen Kumar","doi":"10.1016/j.cct.2025.108005","DOIUrl":"10.1016/j.cct.2025.108005","url":null,"abstract":"<div><h3>Background</h3><div>Assessing and managing symptoms has a survival benefit for patients with advanced cancer. However, rural cancer patients have difficulty accessing services to address symptoms. Technology may offer one solution; however, little work has been done to specifically leverage technology-based solutions to deliver high quality supportive care in rural settings.</div></div><div><h3>Methods</h3><div>Nurse AMIE (Addressing Malignancies in Individuals Everyday) is a 2-year, Phase III randomized controlled efficacy trial to investigate the use of a tablet-based symptom management and supportive care intervention to improve overall survival among 344 advanced cancer patients living in rural areas. Participants are randomized on a 1:1 basis to the Nurse AMIE intervention or a usual care group that receives a binder with written supportive care materials. Intervention participants are asked to access the Nurse AMIE application daily using the study-provided tablet to answer symptom questionnaires regarding their level of pain, fatigue, sleep, and distress. After receiving an empathic response from Nurse AMIE, participants are offered a guideline concordant self-care intervention to address their symptoms. The trial is powered to detect a 19 % difference in overall survival between groups at 2 years. Secondary outcomes include symptom severity, function, quality of life, patient-reported outcomes, and cost-effectiveness.</div></div><div><h3>Conclusions</h3><div>Nurse AMIE is the first trial to apply and rigorously assess the effect of ongoing symptom assessment and management on overall survival among rural, advanced cancer patients. Results from the Nurse AMIE trial will provide evidence of the efficacy of delivering a high-quality, technology-based supportive care program among underserved rural populations.</div><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> registration number <span><span>NCT05221606</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 108005"},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable buprenorphine during transition out of prison: A pilot partially randomized preference trial protocol","authors":"Justin Berk ,&nbsp;Max Cook ,&nbsp;Megan Martin ,&nbsp;Joshua D. Lee ,&nbsp;Daphne Koinis-Mitchell ,&nbsp;Lauren Brinkley-Rubinstein ,&nbsp;Mari-Lynn Drainoni ,&nbsp;Josiah Rich","doi":"10.1016/j.cct.2025.108004","DOIUrl":"10.1016/j.cct.2025.108004","url":null,"abstract":"<div><h3>Background</h3><div>Individuals involved in the criminal legal system represent one of the most disproportionately affected populations in the opioid overdose crisis. Despite evidence of medications for opioid use disorder (MOUD) reducing overdose mortality, illicit opioid use, and recidivism, most correctional facilities do not offer these treatments. Sublocade and Brixadi, two distinct, branded, formulations of extended-release buprenorphine (XR-B), offer a promising approach to improving MOUD treatment adherence and reducing post-release overdose deaths.</div></div><div><h3>Methods</h3><div>This hybrid pilot study will utilize a partially randomized preference trial (PRPT) design to compare the preliminary effectiveness, feasibility, acceptability and other outcomes between Sublocade and Brixadi initiation. We aim to enroll 60 incarcerated individuals with opioid use disorder who are interested in XR-B and have a scheduled release within 120 days. Participants will choose their preferred injectable treatment or, if ambivalent, be randomly assigned. All participants will receive monthly XR-B injections pre-release and continue for three months post-release, with additional administrative follow-up for another three months. The primary outcome is post-release treatment retention; other outcomes will be assessed using the Proctor taxonomy. Data will be collected using clinical assessments, surveys, and administrative databases.</div></div><div><h3>Discussion</h3><div>This study explores differences in XR-B formulations during the high-risk time of transition out of prison. It combines a hybrid implementation science and preference trial design—two methodologies that can help address the specific challenges of research in carceral environments. By understanding implementation of XR-B in a prison setting, findings can provide valuable insights to guide other facilities in adopting this life-saving treatment.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108004"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationale and design of a race-conscious, school-linked, pilot randomized controlled trial to improve physical activity and dietary behaviors of Black adolescent daughter/mother dyads","authors":"Monique Reed ,&nbsp;Tristan Banks ,&nbsp;Shannon Halloway ,&nbsp;Kendra Julion ,&nbsp;Spyros Kitsiou ,&nbsp;Michael Schoeny ,&nbsp;Barbara Swanson ,&nbsp;Christy Tangney ,&nbsp;Kashica Webber-Ritchey ,&nbsp;JoEllen Wilbur ,&nbsp;Kaitlin Wilhelm ,&nbsp;Charleen Yeager ,&nbsp;Wrenetha Julion","doi":"10.1016/j.cct.2025.107996","DOIUrl":"10.1016/j.cct.2025.107996","url":null,"abstract":"<div><h3>Background</h3><div>Black adolescent females are at increased risk for obesity-related morbidity and mortality as adults compared to non-Hispanic White adolescent females. Few interventions to prevent obesity in Black adolescent females have leveraged the relationship of the daughter/mother dyad. Studies that include mothers tend to use theoretical frameworks that do not explicitly build on this important relationship and have not included mothers' active participation. Additionally, these studies do not include girls older than 12 years. In response, we developed Black Girls Move, a school-linked obesity prevention intervention that addresses these limitations in the extant literature.</div></div><div><h3>Method</h3><div>This pilot randomized controlled trial examines the feasibility, acceptability, and impact of Black Girls Move (BGM), a 12-week obesity prevention intervention. Within four schools, 96 dyads will be randomized to either BGM or daughters-only comparison condition (DOCC) (12 per condition). All daughter/mother dyads (BGM and DOCC) complete self-report measures (i.e., PA, diet, family theoretical measures, racial identity, daughter/mother relationship, social cognitions) at baseline, post-intervention, and 3-months post-intervention. BGM incorporates content and processes derived from Public Health Critical Race Praxis, Family Systems Theory, and Social Cognitive Theory. Specific aims are to determine the feasibility of BGM compared to DOCC on change in PA and dietary intake, and the impact of BGM compared to daughters-only on racial identity, daughter/mother relationship, and social cognitions.</div></div><div><h3>Implications</h3><div>Our long-term goal is to decrease disparities in obesity and associated co-morbidities in Black women. The findings may inform a Phase III efficacy trial of BGM in Black daughter/mother dyads.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 107996"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Written Exposure Therapy for Suicide Prevention (WET-SP): Design and methodology of a randomized controlled trial among military service members psychiatrically hospitalized for suicide risk","authors":"Jaclyn C. Kearns ,&nbsp;Ian H. Stanley ,&nbsp;Denise M. Sloan ,&nbsp;Stacey Young-McCaughan ,&nbsp;Hannah C. Tyler ,&nbsp;Jennifer M. Hein ,&nbsp;Casey L. Straud ,&nbsp;Thomas E. Joiner ,&nbsp;James W. Pennebaker ,&nbsp;M. David Rudd ,&nbsp;Alan L. Peterson ,&nbsp;Brian P. Marx ,&nbsp;for the STRONG STAR Consortium","doi":"10.1016/j.cct.2025.108001","DOIUrl":"10.1016/j.cct.2025.108001","url":null,"abstract":"<div><div>Military service members admitted to inpatient psychiatry for self-injurious thoughts and behaviors (SITBs) represent an at-risk group for continued SITBs and rehospitalizations in the post-hospital discharge period. Yet, there is a paucity of evidence-based interventions designed to be delivered on inpatient psychiatric units to reduce the risk of post-discharge SITBs. To address this gap, our group developed Written Exposure Therapy for Suicide Prevention (WET-SP), which is based on the written disclosure paradigm. This paper describes the design, methodology, and protocol of a randomized controlled trial. The primary objective of this study is to evaluate the efficacy of a novel, brief, scalable, cognitive behavioral therapy—WET-SP—in reducing the incidence and severity of SITBs in active duty military service members, veterans, and their adult military beneficiaries following a psychiatric hospitalization due to suicide ideation, suicide plans, or a suicide attempt.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 108001"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing a response-over-continuous-intervention (ROCI) randomised trial: Implementation in the Phase 2C part (duration ranging) of the PARADIGM4TB trial","authors":"Tra My Pham ,&nbsp;Angela M. Crook ,&nbsp;Katie Rolfe ,&nbsp;Patrick P.J. Phillips ,&nbsp;Suzanne M. Dufault ,&nbsp;Matteo Quartagno ,&nbsp;on behalf of UNITE4TB Work Package 2","doi":"10.1016/j.cct.2025.108002","DOIUrl":"10.1016/j.cct.2025.108002","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Treatments for tuberculosis (TB) are often long and complicated. Standard 2-arm non-inferiority trials have been used to evaluate shorter durations of treatment regimens. The new response-over-continuous-intervention (ROCI) trial design has recently been proposed as a practical alternative for optimising some continuous aspect (e.g. treatment duration) of treatment administration.</div></div><div><h3>Methods</h3><div>We demonstrate the use of simulation for designing a ROCI trial in the TB setting. We use the Phase 2C part (duration ranging) of the PARADIGM4TB trial as a case study to illustrate the simulation procedure and the important design considerations to be explored in simulation. Phase 2C of PARADIGM4TB aims to optimise durations of novel treatment regimens, compared to a 6-month standard-of-care treatment regimen, with the aim to support advancement to Phase 3 trials.</div></div><div><h3>Results</h3><div>A ROCI design randomising 200 patients to 5 equally spaced duration arms of the novel treatment regimen (with an additional 40 patients randomised to the standard-of-care treatment regimen) is sufficient to achieve reasonable power to identify the optimal duration in a range of scenarios. Modelling the duration-response curve with a fractional polynomial model of degree 1 improves power to select shorter durations compared with pairwise comparisons. A design with 5 durations of the novel regimen is preferred to a design with 3 durations, because of the improved operating characteristics in scenarios where the duration-response curve is not flat.</div></div><div><h3>Conclusions</h3><div>The ROCI design is an appealing design option for TB treatment trials. The design of ROCI trials can be done by conducting simulation studies to explore key design considerations.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 108002"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telehealth engagement and treatment strategies for adults living with alcohol use disorder: A sequential multiple assignment randomized trial protocol","authors":"Erin E. Bonar ,&nbsp;Kelley Kidwell ,&nbsp;Lyndsay Chapman ,&nbsp;Maureen A. Walton ,&nbsp;Kai Zheng ,&nbsp;Carrie Bourque ,&nbsp;Deborah Manderachia ,&nbsp;Olivia E. Robinson ,&nbsp;Alaa A. Eissa ,&nbsp;Shayla E. Dailey ,&nbsp;Frank Dolecki Jr ,&nbsp;Olivia D. Teasdale ,&nbsp;Alanah NanCoff ,&nbsp;Emily E. Chizek ,&nbsp;Tyleah S. Tyner ,&nbsp;Alesha L. Miller ,&nbsp;Lewei (Allison) Lin","doi":"10.1016/j.cct.2025.108003","DOIUrl":"10.1016/j.cct.2025.108003","url":null,"abstract":"<div><h3>Background</h3><div>Treatment rates for alcohol use disorder (AUD) among adults in the United States (US) are low. Healthcare systems with electronic health records (EHRs) could identify those experiencing AUD and conduct outreach followed by treatment to reduce drinking and/or AUD symptoms. Here, we describe the protocol for a sequential, multiple assignment, randomized trial (SMART) of multiple technology-driven adaptive interventions (ADIs) to increase AUD care and improve outcomes among adults within a large healthcare system.</div></div><div><h3>Methods</h3><div>We plan to enroll 400 adults in this two-stage SMART. Potential participants identified by alcohol indicators in the EHR are screened for eligibility criteria: current drinking, AUD, and lack of current AUD psychotherapy treatment. Participants are randomized to Stage 1 interventions: 1 brief motivational interviewing (MI)-focused phone session, or 4 weeks of interactive therapeutic messaging delivered via a patient-portal like system. Non-responders at a 4-week post-test are re-randomized to an enhanced dose of their Stage 1 intervention (i.e., additional phone session or 4 weeks of messaging) or to an 8-session MI-Cognitive Behavioral Therapy (MI-CBT) protocol via video/phone. Outcomes (e.g., drinking, treatment utilization) are measured at 4-, 8-, and 12-months post-enrollment.</div></div><div><h3>Conclusions</h3><div>This innovative SMART evaluates critical technology-driven ADI strategies within an AUD engagement and care model. We will identify the most effective initial strategy (phone session vs. portal messaging) and, among non-responders, we will assess the most effective follow-up strategy (additional Stage 1 dose vs. MI-CBT). Outcomes will inform the utility of scalable ADIs to engage and improve outcomes for patients with untreated AUD.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> #<span><span>NCT05594238</span><svg><path></path></svg></span>. University of Michigan HUM00210546.</div><div>NCT registration: <span><span>NCT05594238</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"156 ","pages":"Article 108003"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-in-1 adaptive design with dose optimization accounting for ranked dose response","authors":"Man Jin ,&nbsp;Pingye Zhang","doi":"10.1016/j.cct.2025.107999","DOIUrl":"10.1016/j.cct.2025.107999","url":null,"abstract":"<div><div>In oncology clinical trials, seamless 2-in-1 adaptive designs allow mid-trial adaptations on the development pathways to expedite drug development. In this paper, we propose a 2-in-1 adaptive design that allows the expansion of a Phase 2 trial, starting with multiple doses, into a Phase 3 confirmatory trial with one selected dose that demonstrates promising efficacy. The rank of the selected dose will be accounted for in the statistical testing. Simulations have been performed to assess the Type I error and power. The proposed 2-in-1 design can offer attractive operating characteristics, particularly when treatment effect is delayed.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 107999"},"PeriodicalIF":2.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating health insurance selection for in vitro fertilization (IVF) benefits: A study protocol","authors":"Olumayowa Dayo ,&nbsp;Victoria Turcotte ,&nbsp;Breanna Reyes ,&nbsp;Ricardo E. Flores Ortega ,&nbsp;Bonnie N. Kaiser ,&nbsp;Gregory A. Aarons ,&nbsp;Sara B. McMenamin ,&nbsp;H. Irene Su ,&nbsp;Sally A.D. Romero","doi":"10.1016/j.cct.2025.107998","DOIUrl":"10.1016/j.cct.2025.107998","url":null,"abstract":"<div><h3>Introduction</h3><div>A large public university added health insurance coverage of 50 % co-insurance for up to two cycles of in vitro fertilization (IVF) to eligible faculty and staff.</div></div><div><h3>Methods</h3><div>We describe the design and conduct of a randomized controlled trial to evaluate the effectiveness of a health insurance educational intervention on health insurance literacy and IVF benefit utilization. The intervention materials included 1) Key insurance terms; 2) Examples of premiums and deductibles across the insurance plan options; 3) Examples of how premiums and deductibles affect out-of-pocket costs; and 4) A guide to find in-network providers/facilities. The primary outcome is health insurance literacy. Secondary outcomes are IVF services and insurance benefit utilization, out-of-pocket costs, and financial hardship related to fertility care. We will integrate mixed methods data to explore whether the intervention was effective, feasible, acceptable, and appropriate.</div></div><div><h3>Results</h3><div>Among 394 faculty and staff screened, 217 (55 %) reproductive-aged (18 to 50 years) employees consented, completed the baseline survey and were randomized in a 2:1 fashion. Participants were female (81 %), married (63 %), and worked as a staff employee (72 %). At baseline, approximately 39 % reported an infertility diagnosis, and 28 % had undergone prior IVF treatment. Participants reported feeling slightly confident when using their health insurance plans and moderately confident being proactive when using their health insurance.</div></div><div><h3>Discussion</h3><div>Our goal is to improve health insurance literacy and utilization of health insurance benefits for IVF care, thereby expanding family-building options for reproductive-aged individuals.</div><div>Trial registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span> Identifier: <span><span>NCT05663645</span><svg><path></path></svg></span></div><div><span><span>https://clinicaltrials.gov/study/NCT05663645</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 107998"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of an occupational intervention for quality of work life in ADHD: A randomized controlled trial protocol","authors":"Chloé Voyer ,&nbsp;Marc Corbière ,&nbsp;Patrizia Villotti ,&nbsp;Alina N. Stamate ,&nbsp;Geneviève Sauvé","doi":"10.1016/j.cct.2025.107997","DOIUrl":"10.1016/j.cct.2025.107997","url":null,"abstract":"<div><h3>Background</h3><div>While psychosocial interventions for ADHD in children are well-established, there is a gap in addressing ADHD symptoms that persist into adulthood, particularly those impacting occupational functioning. Adults living with ADHD often face challenges in the workplace related to time management, regulating attention, task prioritization, and meeting deadlines.</div></div><div><h3>Methods</h3><div>This study will evaluate the efficacy of a workplace intervention designed to improve the quality of work life in adults living with possible ADHD. A single-blind randomized controlled trial will compare an 8-week virtual psychosocial intervention to an active control group, with quality of work life as the primary outcome. Secondary outcomes will include self-reported measures related to work such as job satisfaction, psychological needs and well-being, self-esteem, self-efficacy, cognitive functioning, self-compassion, and quality of work relationships. Outcomes will be assessed at baseline, post-intervention, and at 3, 6, 9, and 12-month follow-up. In parallel, an optional awareness raising video will engage workplace stakeholders to improve ADHD literacy, reduce stigma, and offer neuroinclusive management strategies. Intention-to-treat analyses will use linear mixed-effects models.</div></div><div><h3>Discussion</h3><div>A participatory research approach was used to co-design the intervention material with workplace managers, community representatives, service providers and adults with lived experience. The research team will disseminate findings in scientific journals, conferences, and by sharing bilingual intervention materials with service providers and adults living with ADHD. This study fills a gap in addressing ADHD in the workplace, with findings that will inform intervention practices and improve workplace inclusion.</div><div><em>Trial registration:</em> This study was registered at ClinicalTrials.gov (<span><span>NCT06774378</span><svg><path></path></svg></span>) on January 17, 2025.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"155 ","pages":"Article 107997"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a monoclonal antibody against respiratory syncytial virus, clesrovimab, in infants and children: Comprehensive rationale and study design for the late-stage clinical trials","authors":"Anushua Sinha ,&nbsp;Radha A. Railkar ,&nbsp;Luis Castagnini ,&nbsp;Andrea Guerra ,&nbsp;Andrea Likos ,&nbsp;Jeannine Lutkiewicz ,&nbsp;Brian M. Maas ,&nbsp;Xiaowei Zang ,&nbsp;Brad A. Roadcap ,&nbsp;Yoonyoung Choi ,&nbsp;Georges J. Nahhas ,&nbsp;Carmen S. Arriola ,&nbsp;Louis Bont ,&nbsp;Paolo Manzoni ,&nbsp;Octavio Ramilo ,&nbsp;Flor M. Muñoz ,&nbsp;Lyn Finelli ,&nbsp;Andrew W. Lee","doi":"10.1016/j.cct.2025.107995","DOIUrl":"10.1016/j.cct.2025.107995","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. Clesrovimab is a half-life–extended, RSV neutralizing monoclonal antibody for the prevention of RSV disease in infants. This article describes the methodology that enabled the acceleration of two pivotal late-stage clinical trials, CLEVER (MK-1654-004; <span><span>NCT04767373</span><svg><path></path></svg></span>) and SMART (MK-1654-007; <span><span>NCT04938830</span><svg><path></path></svg></span>), for the evaluation of clesrovimab.</div></div><div><h3>Methods</h3><div>CLEVER is a placebo-controlled phase 2b/3 study in healthy preterm and full-term infants, evaluating the efficacy and safety of clesrovimab for the prevention of RSV-associated medically attended lower respiratory tract infection (RSV-MALRI) and RSV-associated hospitalization. SMART is a phase 3 palivizumab-controlled study evaluating the safety, tolerability, and efficacy of clesrovimab, compared with palivizumab, for the prevention of RSV-associated MALRI and RSV-associated hospitalization in infants and children at increased risk of severe RSV disease. Dose selection in these studies was informed using a model-based meta-analysis of phase 1 and 2 clesrovimab trial data. Program acceleration was enabled by designing CLEVER seamlessly, to rapidly progress from phase 2b to phase 3. Additionally, efficacy was extrapolated to the SMART population, based on pharmacokinetic bridging between CLEVER and SMART.</div></div><div><h3>Conclusion</h3><div>The methodology of the accelerated late-stage development of clesrovimab, including the model-informed dose selection approach, the seamless enrollment in the phase 3 portion of CLEVER, and the extrapolation of efficacy from the population in CLEVER to the population in SMART, may be used to inform future trial designs where acceleration is needed to address an unmet medical need.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"157 ","pages":"Article 107995"},"PeriodicalIF":1.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}