Streamlining first-in-human trials with IRT systems

At the recent IRT conference, Genmab USA’s IRT manager, Madeline Tremont, discussed how the company implemented IRT systems for their first-in-human (FIH) clinical trials.

For the first 20 years, Genmab’s FIH trials were paper based and managed without an IRT system, according to Tremont.

IRT helps clinical trials sponsors and sites with drug supply logistics and patient management.

“This meant manual tracking of drug dispensation, subject dosing, and manual processes around inventory and supply,” she said.

“As our drug products began to increase in effectiveness in more recent years, our trials were growing. So it became way too cumbersome to manage these trials without an IRT system. It was decided that we needed to migrate the paper trials to IRT trials.”

Madeline Tremont, IRT manager, Genmab USA

Tremont explained that to do so, they had to collect all current and historic subject and inventory data at the site and depot and align that with the IRT system implementation. The goal was to have all data current and accurate to avoid delays to the study before the IRT goes live.

It was just last year that Genmab decided that all trials, including FIH trials, must have an IRT system implemented at the start, Tremont noted.

“So as you can imagine, this came with many challenges across our organization,” she said.

Implementation challenges & benefits

Tremont described some of the challenges when applying IRT for FIH clinical trials, which included:

• Challenging, complex, and/or vague protocols

• Knowing the study will have changes/protocol amendments down the line

• Upfront investment, resources, and time

• Limited IRT experience and resistance among early phase clinical teams

She said that the first challenge Genmab experienced overall was related to protocols.

“Sometimes early phase trials have ultra complex language around many different drug types and complex dosing schedules and possibilities,” Tremont said.

“And on the other hand, you have protocol language that’s so vague, [for example], it says a subject could change dose levels or could change visit schedules without clarifying what that even would mean, making it hard to build IRT systems around that.”

Another challenge was getting stakeholders on board. “So many of our early phase clinical stakeholders may argue that why would we put in that time in investment and effort upfront to implement an IRT system when we’re just going to have to go back and change it, which will be more costly and then potentially delay the trial or dosing or what have you,” she said.

And because of that mindset, Tremont explained that those early phase clinical stakeholders resisted IRT systems.

Aside from the challenges, one of the primary benefits of having an IRT system is leveraging their digitalization capabilities to streamline subject management, drug supply, and cohort management, according to Tremont.

She went on to list a few more benefits, including:

• System availability for possible study expansions

• Integrations

• Availability of audit trail/data for regulatory compliance

• Avoiding data migration to IRT system if trial expands

“Having this data available at our fingertips and ready for internal reviews, audits, regulatory inspection can be such a game changer for early phase trials,” she said.

Tremont added that “scalability and having the system already in place for the future and avoiding a costly, timely, risky data migration is also crucial.”

IRT design considerations

Implementing an adaptive design to support evolving trial needs was key to Genmab’s IRT design.

“We have system flexibility,” Tremont said.

“This could mean the ability for the end user to add a new cohort, add a new dose level, or change a drug type from local to centrally sourced. Also, allowing dose modifications or holds within subject visits or just kind of subject level flexibility overall.

“Planning for the known unknowns,” she continued.

Tremont shared how user-friendly interfaces were key to enhancing user experience, minimizing errors, and ensuring higher user compliance.

“I think this is especially important with first-in-human trials where the sites or the sponsors may not be as comfortable, they may not be as confident. Having these user-friendly systems can boost confidence and make them feel comfortable using it,” she said.

Additional key design considerations include when to deviate from vendor standards and differentiating wants from needs.

“Really work with your provider to flesh out your requirements, solution, your needs within the existing product before adding really highly customized features and modules,” Tremont suggested.

“In our experience, in some of our early phase trials that are highly customized, we end up pulling out those features down the line, or we must change things down the line. So the simpler the better.”

Ultimately, simplicity can lead to faster implementation, reduced costs, and overall better trial, she emphasized.

Quotes have been lightly edited for clarity.

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