In this interview, we met with Dr. Puneet Arora, Chief Medical Officer at Skye Bioscience, to explore the intricacies of their CBeyondTM phase 2 trial. Dr. Arora discusses strategies for patient adherence, safety measures, digital health integration, and combination therapies, offering a comprehensive view of the trial’s design and execution.
Moe Alsumidaie: How do you ensure patient adherence in the 26-week CBeyond TM trial with nimacimab and a GLP-1 agonist?
Puneet Arora: Ensuring patient adherence in a 26-week trial involves strategic design and patient engagement. Our trial features a monotherapy arm and a combination arm with semaglutide. This design benefits patients, as 2 out of 3 participants receive either nimacimab or semaglutide or both. This minimizes placebo use and enhances engagement which is further reinforced through regular advice on diet and lifestyle interventions. We believe these strategies will mitigate adherence issues.
Additionally, we’ve partnered with an experienced vendor for participant retention services, including regular outreach and feedback mechanisms. Our 18 U.S. sites are carefully selected for their experience in obesity trials, ensuring comprehensive support for participants. These measures collectively create a supportive environment that encourages adherence and retention throughout the trial.
Moe Alsumidaie: What safety measures are in place for neuropsychiatric concerns with nimacimab?
Puneet Arora: Patient safety is paramount, especially given the history of neuropsychiatric side effects with first-generation CB1 inhibitors like rimonabant. Although nimacimab is a new-generation antibody with peripheral restriction, meaning it doesn’t penetrate the CNS, we remain vigilant. In our Phase 1b study which enrolled 84 participants, 63 received  active drug, and we observed no meaningful rate of CNS adverse events, which is reassuring. However, we’ve implemented a comprehensive set of assessments for potential adverse neuropsychiatric events, which we developed in close discussion with the FDA. This includes neurological exams and standardized questionnaires like the C-SSRS suicidality scale, cognitive function tests, and mood assessments. An independent data safety monitoring board will also review the data regularly. These measures ensure that we can detect and address any safety concerns promptly, maintaining the highest standards of participant safety.
Moe Alsumidaie: How do you integrate at-home sleep analysis devices in the CBeyond TM trial?
Puneet Arora: Digital health technologies are revolutionizing clinical trials by enabling decentralized data collection. Our trial uses the DREEM Headband and ring device to measure sleep quality and oxygen saturation. These devices allow us to collect data in a non-invasive, at-home setting, which is less burdensome for participants than traditional sleep studies requiring overnight lab stays. The main challenge lies in the setup and training. We’re collaborating with Beacon Biosignals, the group who developed the DREEM Headband to ensure proper training for both sites and participants. The data is transmitted via Bluetooth directly to a database, reducing the risk of data loss or errors. We’ve selected five experienced sites to conduct this sub-study, ensuring adequate training and troubleshooting support for participants. This setup allows us to gather valuable insights into sleep quality and its relationship with obesity while refining our approach to decentralized trials.
Moe Alsumidaie: What strategies ensure robust trial endpoints for weight loss and metabolic outcomes?
Puneet Arora: As an endocrinologist, I understand that obesity is intrinsically linked to metabolic health. Our trial’s primary endpoint is weight loss, and we’ve powered the monotherapy arms to detect this signal robustly. We’re also exploring combination therapy with a smaller cohort to understand how these mechanisms can work together. For secondary endpoints, we’re focusing on body composition using DEXA scans to measure lean and fat mass. This is crucial because preserving lean mass during weight loss helps maintain metabolic rate and prevent weight regain. Additionally, we’re measuring biomarkers like leptin, adiponectin, and inflammatory markers to assess the broader metabolic impact. These comprehensive assessments will provide a holistic view of how our treatments affect weight and metabolic health, ensuring the trial’s findings are robust and reliable. By integrating these strategies, we aim to deliver meaningful insights into the efficacy and safety of our interventions.
Moe Alsumidaie: How does the combination therapy impact trial complexity in patient management?
Puneet Arora: We’ve designed the trial to minimize complexity by treating semaglutide as a standard of care, which is not blinded. This approach simplifies patient management and dosing schedules. Participants follow a weekly dosing schedule for nimacimab or placebo, which aligns with semaglutide’s administration. This setup is straightforward and the dose of semaglutide is titrated carefully to reduce intolerance and the potential for drug-drug interactions. Participants are generally excited about receiving semaglutide, a well-known drug and this enhances their engagement and adherence. By streamlining the trial design, we can focus on gathering valuable data on the combination therapy’s efficacy and safety. This approach simplifies the trial process and maximizes the potential for meaningful outcomes, providing a clear path forward for future research and development.
Moe Alsumidaie: What challenges arise in conducting a multi-site trial, and how do you ensure consistency?
Puneet Arora: Conducting a multi-site trial requires solid partnerships and meticulous planning. We’ve partnered with a trusted CRO to ensure consistent trial execution across all sites. Site selection is critical, and we’ve chosen 18 experienced sites capable of recruiting and managing participants effectively. Frequent and transparent communication is essential, and we’re maintaining regular contact with sites through investigator meetings and ongoing support. We’ve implemented robust data collection tools like ePROs and EDC to minimize transcription errors and ensure data integrity. By leveraging electronic resources, we reduce the burden on patients and sites, streamline data management, and enhance the trial’s overall efficiency. These efforts ensure that we maintain high consistency and reliability standards across all trial locations, ultimately contributing to the study’s success.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
