Rituximab and Abatacept for Prevention or Reversal of Type 1 Diabetes

• Status: Suspended
• Trial end date: 2026-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is a clinical trial testing sequential therapy with rituximab followed by abatacept in individuals destined to develop clinical type 1 diabetes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Juvenile Diabetes Research Foundation; National Institutes of Health (NIH)
• Treatments: Abatacept; Rituximab

Criteria

Inclusion Criteria:

1. Participant in TrialNet Pathway to Prevention Study (TN01).

2. Age ≥ 8 years old at time of enrollment in this trial

3. Participant (or parent or legal guardian if the participant is a minor) is willing to provide Informed Consent.

4. Individuals <18 years of age at time of enrollment must have had a TrialNet-conducted OGTT demonstrating abnormal glucose tolerance within 7 weeks (52 days) of the baseline visit (visit 0).

5. Individuals ≥18 years of age at time of enrollment must have had two consecutive TrialNet conducted OGTTs demonstrating abnormal glucose tolerance, the most recent of which must have been within 7 weeks (52 days) of the baseline visit (visit 0).

6. The participant must be positive for two or more diabetes-related autoantibodies on two occasions. The second occasion must occur within the six months prior to study drug administration, but does not need to involve the same two autoantibodies as were found on the first occasion. The autoantibodies that are to be confirmed are anti-GAD65, anti-ICA512, anti-insulin (MIAA), ZnT8 and/or ICA.

7. Weigh at least 20 kg.

8. If participant is female with reproductive potential, she must have a negative pregnancy test at screening be willing to avoid pregnancy for duration of the treatment period.

9. Willing to forego other forms of experimental treatment during the study.

10. Willing and medically acceptable to postpone live vaccine immunizations for 3 months after treatment.

Exclusion Criteria:

1. Diabetes

2. Immunodeficient or have clinically significant chronic lymphopenia

3. Require use of other immunosuppressive agents

4. Chronic active infection other than localized skin infections.

5. Active infection at the time of infusion.

6. A positive PPD or Quantiferon test, or history of previous treatment for TB.

7. Vaccination with a live virus within 4 weeks prior to enrollment.

8. Vaccination with a killed virus within 4 weeks prior to enrollment.

9. A history of confirmed infectious mononucleosis within the 3 months prior to enrollment, as documented by EBV serology.

10. Not up-to-date on current immunizations

11. Laboratory or clinical evidence of acute infection with EBV or CMV, either via serology or PCR.

12. Serological evidence of current or past HIV, Hepatitis B or Hepatitis C infection.

13. Be currently pregnant or lactating, or anticipate getting pregnant within 2 years and 4 months of enrollment

14. Chronic use of steroids or other immunosuppressive agents.

15. Known and untreated hypothyroidism or active Graves' disease at enrollment.

16. Administration of a monoclonal antibody within the year before enrollment.

17. History of malignancy.

18. Use of exogenous insulin or any other anti-hyperglycemic drugs.

19. Any condition that, in the opinion of the investigator, would interfere with the study conduct or the safety of the participant.

20. Have severe obesity: adults BMI ≥ 40; children BMI-z score ≥ 2.0.