Tag: Clinical trial

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First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe

Fractyl Health has received regulatory approval in the Netherlands to start the first-ever clinical trial for a gene therapy to treat type 2 diabetes. The upcoming Phase I/II clinical trial will test the safety and preliminary efficacy of RJVA-001, a gene therapy designed to locally deliver GLP-1 receptor agonist drugs with the goal of reducing the side effects associated with oral administration. 

“GLP-1 medicines have changed what is possible in obesity and type 2 diabetes, but they require chronic, high-dose systemic exposure that many patients cannot or do not sustain,” said Harith Rajagopalan, MD, PhD, co-founder and CEO of Fractyl Health. “RJVA-001 takes a different path: a potential one-time, pancreas-targeted gene therapy designed to enable the body to produce GLP-1 in response to meals: physiology, not pharmacology.” 

Based in Burlington, Massachusetts, Fractyl Health develops novel approaches to treating obesity and type 2 diabetes. The company’s lead program, an endoscopic procedure to maintain weight loss after discontinuing GLP-1 treatment for obesity, is currently being evaluated in a pivotal clinical trial. 

RJVA-001 leverages an engineered version of the human insulin promoter to trigger the production of GLP-1 in pancreatic beta cells when glucose levels rise after eating. The gene therapy is delivered using a minimally invasive endoscopic infusion directly into the pancreas, which is guided by ultrasound. 

The Phase I/II study will evaluate the safety, tolerability, and preliminary efficacy of three escalating doses of the gene therapy. Participants will include adults with type 2 diabetes who have previously responded well to oral GLP-1 treatment yet continue to experience difficulties controlling their blood sugar levels. 

“With this authorization, RJVA-001 becomes the first AAV gene therapy candidate to enter clinical development for type 2 diabetes,” said Rajagopalan. “We expect to dose the first patient and report initial data in the second half of 2026.”

Later this year, Fractyl expects to expand the study to additional sites in Australia, where the company has already submitted a clinical trial application and is currently awaiting a response from regulators. 

RJVA-001 will be the first candidate from Fractyl’s Rejuva platform to enter clinical development. This smart GLP-1 gene therapy platform focuses on the development of next-generation adeno-associated virus (AAV)-based gene therapies that are locally delivered to the pancreas. Another candidate developed through this platform includes a dual GIP/GLP-1 gene therapy to treat obesity, currently in preclinical development.  

“For decades, we have managed [type 2 diabetes] as a chronic, progressive disease that inevitably worsens over time. With this authorization, we are preparing to test, for the first time in humans, whether a one-time, pancreas-targeted gene therapy delivered via a routine endoscopic procedure could provide durable metabolic control by enabling physiologic, nutrient-responsive GLP-1 expression at the source of disease,” said Jacques Bergman, MD, PhD, professor of gastrointestinal endoscopy and deputy chair of the department of gastroenterology and hepatology at Amsterdam UMC, and a principal investigator of the upcoming clinical trial. 

“Patients who remain inadequately controlled despite maximally tolerated GLP-1 receptor agonists and multiple oral agents represent a population with significant unmet need. If successful, RJVA-001 could transform how we think about [type 2 diabetes], from a chronic disease you manage every day to one that could potentially be treated once.”

The post First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe appeared first on Inside Precision Medicine.

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CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial

Nature Medicine, Published online: 12 May 2026; doi:10.1038/s41591-026-04362-1

In a first-in-human trial combining the transplantation of CD33-negative CRISPR-edited hematopoietic cells with the CD33-targeted antibody–drug conjugate gemtuzumab ozogamicin, all transplanted patients achieved primary engraftment, and the treatment was well tolerated.

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The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial

Nature Medicine, Published online: 10 May 2026; doi:10.1038/s41591-026-04408-4

As presented at the 2026 ESC Heart Failure Congress, in a phase 2 randomized trial in patients with heart failure with reduced left ventricular ejection fraction after myocardial infarction, treatment with CDR132L, an antisense oligonucleotide inhibitor of miR-132, was well tolerated but did not have a significant effect on measures of left ventricular structure or function.

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Medical Marijuana Initiation and Simulated Driving Performance Among Mid-to-Late-Life Adults With Chronic Pain: Prospective Observational Feasibility Cohort Study With Matched Controls

Background: Marijuana initiation among adults aged 50 years and older has increased substantially. Although acute tetrahydrocannabinol exposure can impair psychomotor function, less is known about how real-world medical marijuana initiation relates to functional tasks such as driving in mid-to-late life. Objective: The objective of our study was to evaluate the feasibility of recruiting and retaining adults aged 50 years and older, who are newly registered for medical marijuana, and matched non–marijuana-using controls, into a longitudinal high-fidelity driving simulator protocol, and to explore preliminary associations between medical marijuana initiation and simulated driving performance. Methods: This prospective, nonrandomized feasibility cohort study enrolled adults aged 50 years and older who are newly registered in the Florida Medical Marijuana Use Registry, along with age-, race-, and sex-matched controls. Assessments occurred at baseline (T1; preinitiation) and at 1 month (T2). Primary feasibility outcomes included recruitment, retention, simulator completion and tolerance, and exposure verification. Exploratory outcomes included reaction time and divided attention (DA) performance, which are measured using an immersive, high-fidelity driving simulator. Results: Recruitment and exposure verification procedures were feasible, but simulator sickness contributed to substantial missing data. Exploratory analyses suggested group differences in select DA outcomes at T2. At T2, reaction time to DA situation 3 (DA3) was significantly shorter in the medical marijuana group (n=14, mean 2.57, SD 1.63) than in the control group (n=7, mean 5.79, SD 4.32; =−2.50, =.02, =−1.11, 95% CI −2.04 to −0.16). These findings should be interpreted cautiously, given the small sample size, missing data, and multiple comparisons. Conclusions: A prospective protocol examining medical marijuana initiation and simulated driving among mid-to-late-life adults is feasible, but future studies should incorporate design and analytic refinements to address simulator sickness and missing data and to better characterize exposure timing and patterns. Trial Registration: ClinicalTrials.gov NCT04629716; https://clinicaltrials.gov/study/NCT04629716
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Development and validation of a comprehensive prevention-focused intervention package for problematic digital technology use among youth: a multi-site study protocol

BackgroundProblematic use of digital technology among children, adolescents, and young adults is associated with adverse health, behavioural, interpersonal, social, academic and vocational outcomes. Most existing research focuses on treatment oriented interventions. Prevention focused interventions are limited. This is especially true for the low- and middle-income countries. There is a need for structured prevention approaches that involve youth, parents, and teachers.ObjectivesThis study aims to develop and validate a comprehensive package of prevention-focused interventions targeted at problematic use of digital technology among youth.MethodsThe study will be conducted across six sites in India. It will use a sequential mixed-methods design. Literature review, stakeholder interviews, and expert consensus shall be used for intervention development. This will be guided by established frameworks for complex interventions. Validation will be carried out using a quasi-experimental pre–post design. Quantitative measures will assess changes in knowledge, skills, confidence, and decision-making, as well as feasibility and acceptability. Qualitative methods will be used to assess engagement, delivery quality, and contextual factors.Expected outcomesThe study will lead to a modular prevention-focused intervention package with evidence of feasibility and acceptability. Findings will inform future larger scale implementation and evaluations.ConclusionThis protocol outlines a structured approach to development of a prevention-focused intervention targeted at problematic digital technology use among youth. The focus on prevention, stakeholder involvement, and real-world settings supports relevance for public health practice and policy.Clinical trial registrationhttps://ctri.nic.in/Clinicaltrials/login.php, identifier CTRI2026/03/105278.
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Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study

<strong>Background:</strong> An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. <strong>Objective:</strong> A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. <strong>Methods:</strong> A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. <strong>Results:</strong> The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. <strong>Conclusions:</strong> A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. <strong>Trial Registration:</strong> Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp
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A Sustainable Lifestyle Intervention Among Office Workers: Cluster Randomized Pilot and Feasibility Study

Background: Society faces multiple challenges, including lifestyle diseases and global climate change. Framing health education within sustainable development may enhance motivation for behavior change because proenvironmental behaviors, as well as healthy behaviors, often rely on the same behavior change principles. Combining these perspectives may therefore reinforce health behaviors and climate-friendly choices. Objective: This pilot study aims to explore changes in dietary intake, diet-related carbon footprint, and physical activity among office workers receiving sustainable plus healthy lifestyle (sustainable lifestyle arm) or healthy lifestyle education (healthy lifestyle arm) alone. It also aims to assess the feasibility of the intervention functions, including workshop attendance rate, participants’ dietary goals, social support, and facilitators and barriers to behavior change. Methods: A 2-armed participant-blinded cluster randomized study, including an experimental intervention arm (sustainable lifestyle; n=19) and a control intervention arm (healthy lifestyle; n=14), was conducted in Sweden. The study lasted 8 weeks and included 6 workplace-based workshops and was framed by the behavioral change wheel and the socioecological model. Diet, carbon footprint, and physical activity were assessed using the web-based questionnaires Meal-Q and Active-Q. Attendance rate, individual goals, social support, and facilitators and barriers were assessed using printed questionnaires. Results: The reduction of total diet-related carbon dioxide equivalents (COe) was 0.8 kg and 0.4 kg per day for the sustainable and healthy lifestyle arm, respectively. Also, there was a statistically significant interaction between time and lifestyle when the carbon footprint was expressed as a qualitative aspect of diet, that is, COe kg per 1000 kcal per day (=.05). Moreover, the intake of vitamin C, a marker for fruits and vegetables, increased to 8.0 and 12.5 mg per 1000 kcal per day for the sustainable and healthy lifestyle arms, respectively. In addition, total sedentary time decreased by 0.4 hours per day in the sustainable lifestyle arm, but not in the healthy lifestyle arm. This indicates that the educational workshops in respective arms had different impacts on health behavior over time. Minor differences were found in dietary goals, with the sustainable lifestyle arm setting more goals related to ecological and vegetarian foods. No differences were seen between arms regarding barriers or facilitators. Conclusions: This study suggests that embedding healthy lifestyle recommendations within a sustainable development context may be an efficient way to reduce carbon footprint and increase healthy behavior among office workers. Given the ongoing global epidemic of metabolic diseases, climate change, and environmental degradation, promoting a sustainable lifestyle in a workplace context has the potential to counteract these trends. Trial Registration: ClinicalTrials.gov NCT06698094; https://clinicaltrials.gov/study/NCT06698094
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STAT+: FDA to reconsider treatment for rare cancer after its surprise rejection

Two companies developing a therapy for a rare blood cancer have reached an agreement with the Food and Drug Administration that walked back the agency’s main reason for rejecting the drug in January. 

Pierre Fabre Pharmaceuticals and Atara Biotherapeutics, makers of the drug called Ebvallo, said Thursday that a meeting held in late April with FDA officials ended with the agency agreeing that their already completed, single-arm clinical trial was sufficient to support a review and potential approval. 

When the FDA rejected Ebvallo, the agency said the same study was flawed and the data produced from it was “insufficient” to support the drug’s approval. The drug’s review was conducted by the FDA’s Center for Biologics Evaluation and Research, led at the time by Vinay Prasad. He departed the agency at the end of April. 

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