What side effects are associated with this type of intervention?

Abatacept, which inhibits T cell activation, can cause side effects such as increased risk of infections, headache, nausea, and infusion-related reactions. Rituximab-pvvr, which depletes B cells, is associated with side effects including infusion reactions, infections (such as pneumonia and cellulitis), and potential reactivation of viral infections. Both treatments may also lead to a decrease in immune function, making patients more susceptible to infections.

What prior FDA approvals exist?

The FDA has approved several immunomodulatory therapies for autoimmune conditions, but specific approvals for Type 1 Diabetes (T1D) are limited. Abatacept, which inhibits T cell activation, and Rituximab-pvvr, which depletes B cells, are being studied for their potential in T1D. While these drugs are not yet FDA-approved specifically for T1D, they are approved for other autoimmune diseases such as rheumatoid arthritis. Their mechanisms of action—targeting T cells and B cells—are promising for T1D treatment, as these immune cells play a critical role in the autoimmune destruction of pancreatic beta cells.

What other types of research exist?

Promising novel alternatives for Type 1 Diabetes treatment in 2024 include Teplizumab, an anti-CD3 monoclonal antibody that modulates T cell activity, and Iscalimab, an anti-CD40 monoclonal antibody that inhibits T cell and B cell interactions. Both therapies aim to preserve beta-cell function and delay disease progression by targeting immune pathways involved in T1D.

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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

Summary

This trial is testing whether a combination of two drugs, rituximab-pvvr followed by abatacept, can better preserve insulin production in people newly diagnosed with Type 1 Diabetes compared to rituximab-pvvr alone. Rituximab-pvvr works by reducing harmful immune cells, while abatacept helps calm the immune system. The goal is to see if this combination can improve insulin production and overall diabetes management.

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.

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.

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 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

C-Peptide Response to 2-hr MMTT at 24 months post-randomization

Secondary study objectives

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 at least 3 hours, 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 at least 3 hours, 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.

0 / 12Eligibility criteria met

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.