Tuberous Sclerosis Complex Phase III / IV Trial

Case Study Demographics

• Number of Sites 13 US, 3 UK, 1 Poland, 3 Canada
• Countries US, UK, Poland, Canada
• Services Full service

Background:

A global biopharmaceutical company was conducting a clinical trial for a novel drug intended for the treatment of symptoms associated with Tuberous Sclerosis Complex. The client needed to submit the trial for approval across multiple regions, including the United States, United Kingdom, Poland, and Canada. The key objectives were to meet stringent regulatory timelines, ensure consistent trial enrollment across all sites, and align the strategy across these diverse countries to maximize the chances of successful regulatory approval and timely market access.

Approach:

The client engaged a team of regulatory affairs experts to develop a strategy that would facilitate the smooth submission of the clinical trial application (CTA) in all four countries while ensuring alignment with local regulations and requirements. The strategy focused on close collaboration, efficient communication, and a proactive approach to regulatory challenges.

1. United States:
   • Evestia Clinical secured the use of a Central Institutional Review Board (IRB) to aid in expediting study start up in the United States. We worked closely with the client to develop all necessary documents for submission ensuring that they were in line with FDA and IRB guidelines.
   • A key challenge in the U.S. was ensuring rapid recruitment at clinical trial sites. Close coordination between Evestia Clinical and the client helped achieve the required recruitment targets. The team also maintained ongoing dialogue with the IRB to address any protocol amendments quickly and avoid delays.
2. United Kingdom:
   • The submission to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) required a comprehensive overview of the drug’s safety and efficacy data. The strategy involved submitting a clinical trial authorization (CTA) application while ensuring alignment with the European Medicines Agency (EMA) guidelines, FDA guidelines, and Health Canada guidelines as the clinical trial was recruiting on a global scale.
   • The team worked with local investigators to meet UK-specific ethical review board (IRB) requirements, ensuring that the trial adhered to both local regulations and broader global standards. Recruitment targets were met ahead of schedule, aided by targeted patient outreach and site selection optimization.
3. Poland:
   • In Poland, the team navigated the regulatory landscape set by the Office for Registration of Medicinal Products (URPL), ensuring compliance with the Polish Ministry of Health’s clinical trial laws.
   • Local site management and recruitment were a key challenge in Poland due to logistical hurdles, but proactive engagement with local medical institutions helped build trust with investigators and participants. The collaborative effort resulted in timely approvals and rapid patient enrollment.
4. Canada:
   • The clinical trial submission to Health Canada followed the country’s Clinical Trial Application (CTA) process. This required close attention to Good Clinical Practice (GCP) compliance and ensuring alignment with Canadian clinical trial regulations.
   • The Canadian market had particular considerations in terms of bilingual documentation and recruitment strategies, which were addressed by working closely with Canadian investigators and regional CROs. This helped ensure efficient patient enrollment and on-time regulatory approval.

Collaborative Strategy:

Throughout the process, Evestia Clinical worked closely with local teams in each country to create a unified submission strategy. This approach included:

• Timely Communication: Regular cross-country virtual meetings facilitated the sharing of updates, identified potential regulatory challenges early, and allowed the teams to adapt to changing timelines and requirements.
• Standardized Protocols: The trial protocol was harmonized to the extent possible across all countries to ensure consistency in trial design, procedures, and endpoints, thereby simplifying the submission process.
• Regulatory Intelligence: Expert input was sought from the Evestia Clinical Regulatory Team to address unique national requirements, and these inputs were integrated into the overall submission strategy.
• Enrollment Strategy: The trial enrollment was carefully managed through detailed planning, including site identification, patient recruitment strategies, and recruitment support tailored to each country’s needs. This resulted in meeting enrollment targets for the clinical trial within the stipulated timelines.

Outcome:

The collaborative effort led to the successful submission and approval of the clinical trial in the United States, United Kingdom, Poland, and Canada. All regulatory bodies approved the trial within the expected timelines, and patient enrollment was completed on schedule, ensuring that the trial could progress smoothly without any delays. The client was able to proceed with the trial across these regions and maintain regulatory compliance, which was crucial for the success of the drug development program.

The cross-border cooperation and alignment of strategies not only met the client’s timelines but also positioned the trial for success in future stages of the drug development process. This resulted in a stronger regulatory standing for the drug in each region and expedited pathways for market approval.

About the author

Amber N. Jenkins

Amber N. Jenkins, PhD. is an accomplished Associate Director of Global Regulatory Affairs for Evestia Clinical with over fifteen years of clinical trial experience. Dr. Jenkins has played critical roles in supporting Phase I-IV clinical trials, particularly in Oncology and Rare Disease. She has extensive experience in overseeing regulatory strategies for clinical trials across multiple regions.

With a deep understanding of global regulatory requirements and compliance, Dr. Jenkins leads cross-functional teams to navigate complex regulatory landscapes, ensuring the successful development and approval of clinical trials. A proven leader in managing regulatory submissions, providing strategic guidance, and fostering relationships with health authorities, Dr. Jenkins is dedicated to advancing clinical trials in alignment with industry standards and regulatory expectations.

Tuberous sclerosis complex (TSC) is a rare genetic disorder, often discovered in infancy or early childhood, that causes benign tumors to form in various organs of the body, most commonly in the brain, skin, kidneys, heart, and lungs. It is estimated that between 50,000 and 80,000 new cases are diagnosed worldwide every year. However, the exact number of new cases diagnosed annually can be difficult to determine precisely because of variations in diagnostic practices and underdiagnosis in some regions.

There is no cure for TSC. Early diagnosis and management are important for improving outcomes and leading to a greater quality of life.