Tolerion, Inc ® SUNRISE, DAY, and DAWN Phase 2b Clinical Trials of TOL-3021® for T1 Diabetes

Type 1a diabetes mellitus (T1D) is an auto-immune disease affecting an estimated 1.25 million children and adults in the US alone.  In T1D, the body’s immune system directs a lethal attack on the insulin-producing cells in the pancreas, rendering the patient unable to produce insulin, which is necessary for normal absorption and processing of glucose.  Thus, in T1D all the body’s cells struggle to absorb and process glucose from the bloodstream (taken from the food we eat) for the body’s energy needs.  Left untreated, the glucose accumulates in the blood supply, leading to progressive damage to tissues including the kidneys, heart, blood vessels, nerves, and eyes, and ultimately death.   The only widely available treatment for T1D is manufactured insulin given as one or more injections every day or administered via an insulin “pump”.  Unfortunately, regulating exactly how much insulin the body needs is virtually impossible, even if the patient is very diligent about monitoring their blood glucose levels, estimating their exercise levels and accounting for their food intake over the course of the day and night.  Moreover, it is hugely burdensome on the patient.  Errors in insulin dosing can result in glucose “highs” and “lows” which can be life-threatening, especially if those occur at night.  Persons with T1D live with a disease that is challenging to manage and that can inflict major damage to various parts of the body if not properly controlled. 

In people with T1D, special white blood cells are programmed to attack the beta cells in the pancreas that produce insulin.  In recent years, novel agents have been developed that act biologically by tricking these insulin-seeking white blood cells to no longer “recognize” the insulin-producing cells, thus disrupting their lethal attack and preventing the destruction of pancreatic insulin production.  This targeted therapy ignores all other white blood cells, including those that attack true invaders like bacteria and cancer cells, leaving intact the body’s normal defenses against infection and cancer.

One of these new agents, called TOL-3021, developed by Tolerion, Inc., has been tested in a clinical trial in people with T1D.  That trial compared 12 weeks of active therapy with TOL-3021 with a “control” group who received placebo.  TOL-3021 is given by intra-muscular injection of a small dose (1 mg) once a week.  The results of that trial were encouraging enough that the US Food and Drug Administration (FDA) has granted permission for Tolerion, Inc., to test this treatment in a larger group of T1D patients in order to more clearly assess how well TOL-3021 works in slowing or perhaps even stopping the body’s destruction of its own insulin-producing cells over a 1-year period of time (52 weeks of injections), and to see if it can do so with an acceptable safety profile. 

The studies will be conducted by doctors who specialize in diabetes at various medical centers around the US and will be overseen by the US FDA.  The studies include:

  • The “DiabeteS AUtoimmuNity WithdRawn In New OnSEt and In Established Patients (SUNRISE)” 

This Phase 2 trial will recruit at least 51 adults who have had T1D for less than 5 years.  Two-thirds (N=34) will be randomly assigned to receive 1 mg of TOL-3021 by weekly injection into a large muscle.  One-third (N=17) will be randomly assigned to receive placebo.  They will be treated for 52 weeks and followed for two additional years.

  • The “Diabetes AutoimmunitY Withdrawn in Newonset T1D patients (DAWN)” 

This trial will recruit 210 adults and children 12 years old and older who have had T1D for not more than 100 days after their diagnosis.  Two-thirds (N=140) will be randomly assigned to receive 1 mg of TOL-3021 by weekly injection into a large muscle.  One-third (N=70) will be randomly assigned to receive a placebo.   They will be treated for 52 weeks and followed for two additional years.

  • The “Diabetes AutoimmunitY withdrawn in established T1D patients (DAY)” 

This trial will recruit 350 adults and children 12 years old and older who have had T1D for at least 1 but less than 5 years after their diagnosis.  Two-thirds (N=144) will be randomly assigned to receive 1 mg of TOL-3021 by weekly injection into a large muscle.  One-third (N=70) will be randomly assigned to receive a placebo.   They will be treated for 52 weeks and followed for two additional years.

 

In both studies, neither the study participant nor their clinical center investigator will know whether they are receiving TOL-3021 or placebo – these are “double-blinded” studies.  The main measure of whether the agent works will be a comparison between the TOL-3021 group and the placebo group in the change in pancreatic insulin production between baseline and after 12 months of weekly therapy.  Insulin production will be measured by a test done at the clinical site where small blood samples are taken over 4 hours following a standard meal (Boost) given early in the morning before breakfast.  In addition to the results from this test, investigators will look for other beneficial effects of treatment with TOL-3021 including:

  • Reduction in severe hypoglycemic events
  • Reduction in insulin injections and/or total daily insulin requirement
  • Reduction in glycated hemoglobin (HbA1c, a longterm measure of blood glucose control)
  • Ability to control blood glucose levels

Numerous additional clinical evaluations will be conducted, and additional blood and urine samples will be collected for both research purposes and to support good clinical care of every participant.

The other objective of the studies – in addition to measuring how well TOL-3021 works in preventing progression of T1D – is to definitively determine the safety of TOL-3021 as a biologic agent given weekly over 12 months, and how well study participants tolerate the weekly injections.  The investigators will be assessing safety using various methods throughout all three trials. 

Clinical care will be provided to all study participants along with support and education for them and their families, to achieve target goals of diabetes management throughout the period of study.  The studies will be monitored by the US FDA and a central Institutional Review Board (IRB) for adherence to good clinical practice and best standards of clinical trials conduct.

The results of the studies will be made available to the participants after the studies have fully completed as soon as they are ready for public disclosure.

If these trials of TOL-3021 yield results supportive of efficacy (working to significantly retard or reverse the decline of insulin production over the year of treatment), and an acceptable safety profile, TOL-3021 may be submitted for approval to the US FDA for licensing and marketing for treatment of newly diagnosed and/or established T1D.  This process may require additional research and clinical studies.

For additional information on our protocols go to our Tolerion website here - Tolerion, Inc. and the protocol ClinicalTrials.gov page here - Clinicaltrials.gov SUNRISE Protocol