Teplizumab vs ATG for Type 1 Diabetes

(TN40A Trial)

Overseen By Melissa Parker

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Infections, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug Antithymocyte Globulin (ATG) can delay or prevent progression to Stage 3 Type 1 diabetes more effectively than teplizumab. Participants will receive either 2 infusions of ATG or 14 infusions of teplizumab, with their progress monitored over 12 months. The study seeks individuals diagnosed with Stage 2 Type 1 diabetes, characterized by specific diabetes-related antibodies and changes in blood sugar levels. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant early findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use other drugs that affect blood sugar control within 14 days of screening. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In earlier studies, Antithymocyte Globulin (ATG) showed promise in managing Type 1 diabetes. Researchers found that small doses could slow the loss of insulin-producing cells. The treatment was generally safe, with no major safety issues reported.

Teplizumab has also been researched for its effects on Type 1 diabetes. It reduced the need for insulin and improved some diabetes indicators. Most side effects were mild, such as headaches and stomach problems. Serious side effects were rare and usually unrelated to the treatment.

Both treatments have shown potential in slowing diabetes progression with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Type 1 Diabetes, which typically involve insulin therapy to manage blood sugar levels, Teplizumab and Antithymocyte Globulin (ATG) offer unique approaches. Teplizumab is an immune-modulating antibody that targets the immune system, potentially delaying the progression of Type 1 Diabetes by preserving insulin-producing cells in the pancreas. Researchers are excited about Teplizumab because it tackles the underlying autoimmune process rather than just managing symptoms. On the other hand, ATG is another immune-modulating treatment that depletes certain immune cells, aiming to reduce the autoimmune attack on the pancreas. Both treatments offer new hope by modifying the disease process, which could significantly change how Type 1 Diabetes is managed in the future.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

This trial will compare Antithymocyte Globulin (ATG) and teplizumab for treating Type 1 diabetes. Studies have shown that ATG can slow the disease by protecting insulin-producing cells in the pancreas. It also helps maintain stable C-peptide levels, indicating pancreatic function, and can lower HbA1c levels, which reflect average blood sugar over time. Meanwhile, teplizumab has delayed the onset of advanced Type 1 diabetes. In one study, only 43% of those treated with teplizumab developed full diabetes, compared to 72% in the untreated group. Both treatments show promise in managing Type 1 diabetes and slowing its progression. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals at risk of progressing to Stage 3 Type 1 diabetes. Participants will receive either ATG or Teplizumab and be monitored for a year. Specific eligibility criteria are not provided, but typically include factors like age, health status, and disease stage.

Inclusion Criteria

History of at least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample, with exceptions for ICA and GADA positivity alone

Must meet TrialNet eligibility minimum immunization recommendations

If female with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing

Exclusion Criteria

Prior adverse reactions to heparin

Currently pregnant, lactating, or anticipating pregnancy within the study period

Complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either 2 infusions of ATG or 14 infusions of teplizumab

2 weeks

14 visits (in-person) for teplizumab, 2 visits (in-person) for ATG

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Antithymocyte Globulin (ATG)
• Teplizumab

Trial Overview The study compares two treatments: ATG (2 infusions) versus Teplizumab (14 infusions), to see which is more effective in delaying or preventing the onset of full-blown Type 1 diabetes over a period of 12 months.

How Is the Trial Designed?

Group I: ATG Experimental Treatment 1 Intervention

Antithymocyte globulin (ATG) will be intravenously administered over two days, with a total of 2 infusion periods. The first dose (0.5mg/kg) will be infused over a minimum of 6 hours, and the second dose (2mg/kg) over a minimum of 4 hours with a maximum infusion time for each infusion of 10 hours. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.

Group II: Teplizumab Active Control 1 Intervention

Intravenous infusions of teplizumab will be given for 14 consecutive days. Each infusion takes about 30 minutes. Vital signs will be monitoring for at least 30 minutes after each infusion. If reactions to the infusion occur participants may be monitored for at least 2 hours after the study drug infusion. The total dose for the 14-day course is approximately 11,240 µg/m².

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625016745

Minimum effective low dose of antithymocyte globulin in ... In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12074605/

Therapeutic potential of anti-thymocyte globulin in type 1 ... Results indicated that ATG showed potential in preserving beta-cell function and improving clinical outcomes in recent-onset T1D.

3. diabetesjournals.org diabetesjournals.org/care/article/47/2/285/154034/Low-Dose-Antithymocyte-Globulin-A-Pragmatic

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to ... Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA 1c in new-onset stage 3 type 1 diabetes.

4. trialnet.org trialnet.org/events-news/blog/immunotherapy-proven-slow-t1d-progression-people-newly-diagnosed-now-being-tested

Immunotherapy proven to slow T1D progression in people ... “Both preclinical and clinical data have shown that low-dose ATG can slow the progression of type 1 diabetes,” said Dr. Haller, who is also ...

5. breakthrought1d.org breakthrought1d.org/for-the-media/press-releases/breakthrough-t1d-encouraged-by-results-of-clinical-trial-demonstrating-effectiveness-of-existing-drug-in-new-onset-type-1-diabetes/

Breakthrough T1D Encouraged by Results of Clinical Trial ... Previous studies in new-onset T1D found that it has disease-modifying effects. This study, using an adaptive trial design, successfully tested a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6105329/

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell ... We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration <100 days) ...

7. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0323642

Therapeutic potential of anti-thymocyte globulin in type 1 ... The primary outcomes assessed were preservation of C-peptide levels, glycemic control, and adverse events. Results indicated that ATG showed potential in ...

8. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01773-8/fulltext?rss=yes

ATG as disease-modifying therapy for new-onset type 1 ... Trial investigators concluded that the 0·5 mg/kg ATG dose had an acceptable safety profile and represented a minimal effective dose that could ...

9. trialnet.org trialnet.org/our-research/prevention-studies/atg-stop-t1d

ATG Prevention Study (STOP-T1D) | Type 1 Diabetes ... There were no safety concerns. Researchers remain excited about anti-thymocyte globulin (ATG) in Stage 2 of type 1 diabetes (T1D). TrialNet investigators ...