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Co-stimulatory Blockade

Rituximab + Abatacept for Type 1 Diabetes (TN25 Trial)

Phase 2
Recruiting
Research Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Positive for at least one islet cell autoantibody: GAD65A, mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or ZnT8A
Body weight must be ≥ 20.0 kg for study agent administration
Must not have
A history of confirmed infectious mononucleosis within the 3 months prior to initiating study treatment, as documented by EBV serology (EBV VCA-IgM and VCA-IgG; PCR would be confirmatory)
Chronic active infection other than localized skin infections
Timeline
Screening 3 weeks
Treatment Varies
Follow Up day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36
Awards & highlights

Summary

This trial will test if Abatacept can improve diabetes (T1D) response when used after Rituximab-pvvr. Primary outcome is C-peptide response 24 months after enrollment.

Who is the study for?
This trial is for people aged 8-45 with new onset Type 1 Diabetes who have certain levels of C-peptide, are positive for specific autoantibodies, and meet other health criteria. They must be up to date on vaccinations, not pregnant or planning pregnancy soon, willing to use contraception and follow intensive diabetes management.Check my eligibility
What is being tested?
The study compares the effect of Rituximab-pvvr followed by Abatacept versus Rituximab-pvvr alone on C-peptide response in newly diagnosed Type 1 Diabetes patients. It's a double-blinded trial where participants don't know which treatment they're getting.See study design
What are the potential side effects?
Possible side effects include reactions at the injection site, increased risk of infections due to immune system suppression, potential liver enzyme elevations, and general symptoms like headache or nausea.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My body has antibodies related to diabetes.
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My body weight is at least 20 kg.
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I am up to date with all my vaccinations.
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I am between 8 and 45 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I had infectious mononucleosis confirmed by a blood test in the last 3 months.
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I have a long-term infection that is not just on my skin.
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I have tested positive for TB or have been treated for TB in the past.
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I currently have symptoms of an infection.
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I am using non-insulin diabetes medication.
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I have untreated hypothyroidism or active Graves' disease.
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I have previously participated in a clinical trial with the same medication.
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I regularly use steroids or other drugs that weaken my immune system.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36
This trial's timeline: 3 weeks for screening, Varies for treatment, and day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36 for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
C-Peptide Response to 2-hr MMTT at 24 months post-randomization
Secondary outcome measures
Analysis of changes in immune responses to known diabetes antigens and a neoantigen over time by treatment group
C-peptide AUC Means

Trial Design

2Treatment groups
Active Control
Placebo Group
Group I: Rituximab-pvvr followed by AbataceptActive Control2 Interventions
Rituximab-pvvr will be given by IV infusion over a 3-8 hour period, at a dose of 375mg/m2 on four visits each one week apart, starting at Week 0 of the study. Abatacept will be given by a subcutaneous formulation weekly for 20 months, beginning at Week 16 (Month 4) of the study. Dosing will be determined by weight: Up to 25 kg: 50 mg (0.4 mL); 25 to <50 kg receive 87.5 mg (0.7 mL), and > 50 kg receive 125 mg (1.0 mL).
Group II: Rituximab-pvvr followed by PlaceboPlacebo Group2 Interventions
Rituximab-pvvr will be given by IV infusion over a 3-8 hour period, at a dose of 375mg/m2 on four visits each one week apart, starting at Week 0 of the study. Placebo will be given by a subcutaneous isotonic saline formulation weekly for 20 months, beginning at Week 16 (Month 4) of the study. Dosing will be match to active comparator, determined by weight: Up to 25 kg: 0.4 mL; 25 to <50 kg rec 0.7 mL, and > 50 kg receive 1.0 mL.

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Abatacept works by inhibiting T cell activation through binding to CD80 and CD86, which prevents the full activation of T cells that are responsible for attacking pancreatic beta cells in Type 1 Diabetes. Rituximab-pvvr depletes B cells by targeting the CD20 antigen, reducing the number of B cells that can present antigens to T cells and produce autoantibodies. These mechanisms are crucial for Type 1 Diabetes patients because they aim to preserve beta cell function by reducing the autoimmune response that leads to beta cell destruction, potentially slowing disease progression and improving insulin secretion.
B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes.B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes.Making progress: preserving beta cells in type 1 diabetes.

Find a Location

Who is running the clinical trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Lead Sponsor
2,381 Previous Clinical Trials
4,315,028 Total Patients Enrolled
National Institutes of Health (NIH)NIH
2,736 Previous Clinical Trials
7,507,876 Total Patients Enrolled
Juvenile Diabetes Research FoundationOTHER
234 Previous Clinical Trials
142,107 Total Patients Enrolled
~49 spots leftby Oct 2027