The inside scoop on the CATT1 clinical trial

Partners in clinical trials

Clinical trials are key to bringing new treatments, therapies, and devices for type 1 diabetes (T1D) from the lab to the clinic. Pharmaceutical and biotech companies, which conduct research and help develop and manufacture new therapies, are a critical player in accelerating this process. Companies often partner with clinical researchers at medical centers and hospitals to test their new therapies through clinical trials. These collaborative partnerships are essential for new drugs to move through the pipeline and get to people with T1D.

Spotlight on the CATT1 clinical trial

The CATT1 clinical trial is investigating whether cadisegliatin (TTP399), a glucokinase activator, can reduce hypoglycemic events (low blood sugars) in people with T1D when used alongside insulin therapy. Read on to learn more about the people making the CATT1 clinical trial happen, the science behind cadisegliatin, and how you can get involved.

Breakthrough T1D x vTv Therapeutics

Breakthrough T1D has a long-standing relationship with vTv Therapeutics. After partnering with Breakthrough T1D in 2017, vTv pivoted from type 2 diabetes to T1D. With Breakthrough T1D’s support, vTv launched a phase 2 clinical trial (SimpliciT1) investigating cadisegliatin as an adjunctive therapy for T1D, showing that it improved blood glucose control. Eager to keep the momentum going, the T1D Fund has supported vTv from early 2024 onwards, most recently participating in the company’s latest round of financing to continue to support the ongoing phase 3 trial for cadisegliatin in T1D.

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“Breakthrough T1D has long been a supporter of adjunctive therapies, meaning medicines that can be taken alongside insulin to improve glucose control and other outcomes. Previous clinical trials have demonstrated the potential for cadisegliatin to reduce hypoglycemia and improve HbA1C in people with T1D, and we are excited to support the phase 3 program to advance this therapy toward the clinic where it can be used to address major unmet clinical needs in our community.”

Jonathan Rosen, Ph.D., Director of Research at Breakthrough T1D

Meet the team at UNC

Within the UNC Medical Center, the EnDO CRU is a hub for endocrinologists, clinical researchers, and other experts who work together to lead clinical studies at cutting edge facilities that help bring new transformative therapies to the people who need them most. Within the EnDO CRU, Dr. Klara Klein and Alex Kass are taking the lead on T1D clinical trials—a passion they both share for different reasons.

T1D has been on Dr. Klein’s mind since she was a little girl. “I grew up hearing about diabetes—my mom is an endocrinologist, and it was a frequent topic at the dinner table,” she said. After following in her mother’s footsteps and becoming an endocrinologist herself, Dr. Klein is shocked that insulin—which was discovered over 100 years ago—is still the gold standard for T1D management. In this sense, not much has changed since she was sitting at the dinner table with her parents.

This sentiment inspires her work. “I’ve always been struck by the daily challenges people with T1D face. Even with incredible advances in technology, managing T1D is a constant effort—every meal, every workout, every illness,” she explained. Her true passion is bringing new therapies to fruition that can ease the daily burden of living with T1D until everyone has access to cures. “Being part of research that could improve the lives of people living with diabetes in meaningful ways is both exciting and deeply rewarding.”

Dr. Klein is supported by a passionate and experienced team composed of five endocrinologist sub-investigators, a nurse coordinator, and a research assistant. She also works closely with Kass, who leads the operational side of many different trials within the EnDO CRU.

Kass is one of a few other staff on the team who is also living with T1D, giving him an inside perspective and inspiring his career to help people with diabetes live better lives. “Having type 1 diabetes myself has fueled my passion for both patient care and finding better treatment options,” he explained. “Together, our team’s mission is simple: to run high-quality studies that give people with diabetes access to promising therapies and make their day-to-day lives easier. This shared passion in our group inspires me!”

The team is working hard behind-the-scenes to recruit and care for participants of the CATT1 clinical trial, which is just one of the many studies they are running to help people with T1D.

Everything you need to know about the CATT1 clinical trial

The phase 3 CATT1 clinical trial is investigating whether cadisegliatin can reduce moderate to severe low blood sugar (hypoglycemic) events when used alongside insulin therapy over a period of six months. Hypoglycemia is the most common short-term complication of T1D, and we need to do more to help people with T1D manage their blood sugar to reduce dangerous lows. This clinical trial is trying to do just that.

Based on observations from previous clinical studies, cadisegliatin may be able to lower the risk of hypoglycemia. Participants in the phase 2 SimpliciT1 study showed clinically meaningful improvements in blood sugar control in addition to a 40% reduction in hypoglycemic events compared to the placebo. Nearly 600 participants have received cadisegliatin so far—it’s been well-tolerated and hasn’t increased the risk of diabetic ketoacidosis (DKA).

Dr. Klein, Kass, and their team are actively recruiting for the CATT1 trial over the next three or so months.

Some key eligibility criteria are:

• Minimum of five years since T1D diagnosis
• At least one moderate to severe hypoglycemic event (Level 2 or 3) in the last two months prior to screening
• 18 years of age or older
• HbA1c levels < 9.5%
• Use of a continuous glucose monitor (CGM) for at least three months prior to screening (excluding closed-loop systems)

Clinical classification of hypoglycemic events

Participants, investigators, and care providers will all be unaware of whether the participants are receiving cadisegliatin or the placebo, which will both be given orally. Participants can expect a combination of in-person and virtual visits over a 26-week period. During these visits, the clinical research team will check blood sugar levels, perform other lab tests to assess safety, and provide top-tier T1D care.

At UNC, for the entire length of the trial, participants will have access to a dedicated study team including a nurse coordinator, research assistant, and diabetes specialists. The clinical research team will guide participants through every step of the process—answering questions, reviewing results, providing support—so that people with T1D and their families can feel confident that they are in good hands.

The science behind cadisegliatin

We know that cadisegliatin has been shown to reduce the risk of hypoglycemia in people with T1D (SimpliciT1 study). The next question is: how?

The answer to this question lies in the liver. The liver plays a major role in blood glucose control by taking up excess sugar from the blood and storing it until it’s needed again. To facilitate this, an enzyme called glucokinase in liver cells is activated in response to higher levels of insulin (indicating high blood sugar). This allows liver cells to remove glucose from the blood, bringing blood sugars down to a normal range.

Some of the glucose in the liver is also converted into glycogen, a storage form for glucose. This way, the liver can help increase blood sugar levels when needed, such as in between meals, overnight, or during exercise, to avoid low blood sugar. In this way, glucokinase helps reduce both hyperglycemia and hypoglycemia.

In people with T1D, the pancreas produces little to no insulin, and injected insulin doesn’t reach the liver the same way insulin from the pancreas does. So, glucokinase doesn’t get the signal that allows liver cells to respond to high blood sugar—making hyperglycemia and hypoglycemia worse.

This is where a glucokinase activator like cadisegliatin comes in. It keeps glucokinase in an active state, which restores the ability of liver cells to respond to (and reduce) high blood sugar. Then, in response to low blood sugar, the liver can release some of the sugar it has stored as glycogen into the blood stream. This is why cadisegliatin is being studied in people with T1D— it has the potential to improve blood glucose control in the liver and reduce the risk of highs and dangerous lows, with the goal of easing the daily burden of living with the disease.

Make a difference for yourself and others by participating in clinical trials

The clinical research team at UNC encourages trial participation as an opportunity to contribute to the body of research that may improve T1D care not only for yourself, but for the T1D community. Participants receive continued support at every step of the way—and safety is the highest priority.

By choosing to participate in a trial, people with T1D may gain access to research treatments, drugs, or devices that may make daily life with T1D easier, while receiving top quality diabetes care delivered by renowned medical centers. The data generated from these trials—thanks to the courageous and brave T1D community members who choose to participate—will shape the treatment landscape for future generations of people with T1D. Dr. Klein is one of many investigators who finds the dedication of the T1D community inspiring. “…I am consistently amazed and moved by the generosity of our participants who dedicate their time and energy to help move science forward,” she explains.

“The T1D community is incredibly generous with their time and motivated to help advance care—not just for themselves, but for the type 1 diabetes community and future generations of people who will live with type 1 diabetes. It’s really an honor to be able to work with them.”

-Klara Klein, M.D., Ph.D.

For Kass, it’s personal. By having T1D himself, he can form deeper connections with trial participants and their families. This allows him to keep conversations honest, participate in shared problem-solving, and understand the same day-to-day challenges of living with T1D—all a part of why he’s excited to be a member of the team providing top-tier diabetes care.

“Some of my favorite moments are when a participant or parent says, ‘You get it,’ and we can talk not just about the study, but about what it means to live well with diabetes. Whether it’s troubleshooting a CGM issue, celebrating a small win in blood sugar control, or simply being a dependable point of contact, I value the trust our participants place in us. That trust is what keeps me passionate about this work.”

-Alex Kass, MSN, MBA, RN, CDCES

Without clinical trials, progress wouldn’t be possible. All new therapies, devices, and treatments need to be tested to get from labs and into clinics as quickly and safely as possible. Thank you to every trial participant—in the past, present, and future—for helping us get closer to a world without T1D.