Tolerance Using Plasmid (TOPPLE) Study: Phase 1

Dear TrialNet Family,

As we announce findings from the TOPPLE (Tolerance Using Plasmid in People with T1D) Study published in Diabetes, I would like to take this opportunity to recognize and thank everyone who contributed to testing this new immunotherapy for the first time in people.

The goal of this Phase 1 study was to evaluate the safety and dosing of a new plasmid immunotherapy in individuals diagnosed with type 1 diabetes (T1D) within the past 4 years. In this study, the plasmid delivered proteins combined with immune messengers directly to cells. Findings from the TOPPLE Study confirm that the plasmid immunotherapy was safe and well-tolerated. At each dose level, it was possible to detect the presence of the plasmid and associated immune responses. This opens the door to further research on how to block harmful immune responses related to T1D.

We offer a heartfelt thank you to our amazing participants, families, and research teams. Thanks to your dedication and commitment, we were able to conduct TrialNet’s first Phase 1 study and gain valuable insights for future research.

Sincerely,

Robin Goland, MD
TrialNet Lead Investigator, TOPPLE Study
TrialNet Principal Investigator, Columbia University

Findings from the Tolerance Using Plasmid in People with T1D (TOPPLE) Study were published in Diabetes.

The goal of this plasmid immunotherapy is to help “re-educate” the immune system to stop the autoimmune response that destroys insulin-secreting cells in the pancreas, leading to type 1 diabetes (T1D).

In this study, the plasmid NNC0361-0041 carried four different proteins, including three cytokines and an antigen.

Cytokines are chemical messengers that direct the activity of immune cells.
Antigens are parts of proteins that the immune system reacts with.

Earlier studies in the lab showed the four proteins could reduce the immune attack on insulin-producing beta cells.

The TOPPLE Study enrolled 47 adults between the ages of 18 and 45. All participants had been diagnosed with T1D within the past 4 years. Because this was the first study to test this plasmid immunotherapy in people, we enrolled individuals in small groups to evaluate the safety and dose before enrolling more people.

In the treatment phase of the study, participants received 12 weekly injections of the plasmid or placebo. In the follow up phase, participants were monitored for 12 months.

The plasmid immunotherapy was safe and well-tolerated.
At each dose level, it was possible to detect the presence of the plasmid and associated immune responses. This opens the door to further research on how to block harmful immune responses related to T1D.

TrialNet will continue to evaluate the results of mechanistic studies (evaluating test samples collected during and after the TOPPLE Study) to look for evidence of expected changes in immune function.
TrialNet is continually planning and launching new studies to test ways to stop disease progression. We offer new onset studies for people newly diagnosed with T1D (generally within 100 days of diagnosis) and prevention studies for those in early stage T1D.
If you have a relative with T1D, you’re in a unique position to help researchers learn more about the disease and how to prevent it. TrialNet risk screening can detect the early stages of T1D years before symptoms appear. Screening is free, quick and convenient.

You can order an in-home test kit (that uses a fingerstick), or you can get a blood draw at a local lab or one of TrialNet’s many locations. If screening detects the early stages of T1D, you may be eligible for monitoring and clinical trials aiming to change the course of the disease. Learn more or sign up today at trialnet.org/participate.

A big thank you to our amazing participants who made this research possible!

If you have not reviewed your individual results with your study team, please contact your study team or email us at info@trialnet.org. If you have questions about your study results or results from the overall study, please contact your study team or info@trialnet.org.
If you haven’t already joined the LIFT Study (Long-Term Investigative Follow-Up in TrialNet), we encourage you to do so. This study provides former TrialNet study participants with ongoing monitoring by experts at the forefront of T1D research.

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