Rituximab + Abatacept for Type 1 Diabetes

(TN25 Trial)

Recruiting in Palo Alto (17 mi)

+23 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Must not be taking: Non-insulin glycemic

Disqualifiers: Immune deficiency, Chronic infection, others

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using non-insulin drugs that affect blood sugar control within 7 days of screening. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Rituximab and Abatacept for treating type 1 diabetes?

Research shows that Rituximab, which reduces certain immune cells, has been beneficial in slowing the decline of insulin-producing cells in people with new type 1 diabetes. Abatacept, which affects immune cell activation, has shown temporary effectiveness in new-onset type 1 diabetes, although it did not lead to long-lasting immune tolerance. ^{1 2 3 4 5}

Is the combination of Rituximab and Abatacept generally safe for humans?

Rituximab and Abatacept have been used safely in patients with rheumatoid arthritis, with common side effects including infusion reactions and infections. Premedication with corticosteroids can reduce infusion reactions to Rituximab, and while severe infections are more common with Abatacept, opportunistic infections and malignancies are rare. ^{6 7 8 9 10}

How is the drug combination of Rituximab and Abatacept unique for treating type 1 diabetes?

The combination of Rituximab and Abatacept is unique for treating type 1 diabetes because Rituximab targets and depletes B cells, which are involved in the autoimmune process, while Abatacept modulates the immune response by affecting T cells. This dual approach aims to protect insulin-producing cells in the pancreas, offering a novel strategy compared to standard treatments that primarily focus on managing blood sugar levels. ^{2 4 5 11 12}

Research Team

Kevan Herold, MD

Principal Investigator

Type 1 Diabetes TrialNet Chairman

Stephen Gitelman, MD

Principal Investigator

Type 1 Diabetes TrialNet

Daniel Moore, MD

Principal Investigator

Type 1 Diabetes TrialNet

Eligibility Criteria

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.

Inclusion Criteria

It has been over 4 weeks since I received a live viral vaccine.

My body has antibodies related to diabetes.

I am a man of reproductive age and will use birth control during and for 12 months after rituximab-pvvr treatment.

Exclusion Criteria

I had infectious mononucleosis confirmed by a blood test in the last 3 months.

You have less than 800 white blood cells per microliter of blood.

I have a long-term infection that is not just on my skin.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Rituximab-pvvr is administered by IV infusion over four visits, each one week apart, followed by Abatacept or Placebo subcutaneous injections weekly for 20 months

20 months

4 visits (in-person) for Rituximab, weekly visits for Abatacept/Placebo

Follow-up

Participants are monitored for safety and effectiveness after treatment, including C-peptide response and immune marker analysis

24 months

Regular monitoring every 6 months

Treatment Details

Interventions

• Abatacept (Co-stimulatory Blockade)
• Rituximab (Monoclonal Antibodies)

Trial Overview 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.

Participant Groups

Group I: Rituximab-pvvr followed by Abatacept Active Control 2 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 Placebo Placebo Group 2 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.

Abatacept is already approved in Canada, Japan for the following indications:

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Miami Miami, FL

Joslin Diabetes Center Boston, MA

University of Minnesota Minneapolis, MN

Childrens Hospital of Orange County Orange, CA

More Trial Locations

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2513

Patients Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2896

Patients Recruited

8,053,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Patients Recruited

142,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes. Linsley, PS., Greenbaum, CJ., Speake, C., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rituximab on human in vivo antibody immune responses. Pescovitz, MD., Torgerson, TR., Ochs, HD., et al.[2021]

In a study involving 112 patients with recent-onset type 1 diabetes, abatacept treatment resulted in a 59% higher C-peptide concentration after 2 years compared to placebo, indicating better preservation of β-cell function.

Abatacept was well-tolerated, with few infusion-related adverse events and no significant increase in infections or neutropenia, suggesting it is a safe option for modulating T-cell activity in type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Orban, T., Bundy, B., Becker, DJ., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-lymphocyte depletion with rituximab and β-cell function: two-year results. Pescovitz, MD., Greenbaum, CJ., Bundy, B., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial. Zieliński, M., Żalińska, M., Iwaszkiewicz-Grześ, D., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. Weinblatt, ME., Moreland, LW., Westhovens, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A novel treatment option in rheumatoid arthritis: abatacept, a selective modulator of T-cell co-stimulation]. Dejaco, C., Duftner, C., Wipfler, E., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rituximab and abatacept in rheumatoid arthritis]. Gómez Centeno, T.[2012]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the place of recently approved T cell-targeted and B cell-targeted therapies in the treatment of rheumatoid arthritis? Lessons from global clinical trials. Smolen, JS.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B cell depletion: a novel therapy for autoimmune diabetes? Bour-Jordan, H., Bluestone, JA.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of thyroid remission using rituximab in a patient with type 3 autoimmune polyglandular syndrome including Graves' disease and type 1 diabetes mellitus: a case report. Kurozumi, A., Okada, Y., Arao, T., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of rituximab on human in vivo antibody immune responses. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

B-lymphocyte depletion with rituximab and β-cell function: two-year results. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. [2022]

7. Austria pubmed.ncbi.nlm.nih.gov

[A novel treatment option in rheumatoid arthritis: abatacept, a selective modulator of T-cell co-stimulation]. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

[Rituximab and abatacept in rheumatoid arthritis]. [2012]

10. Canada pubmed.ncbi.nlm.nih.gov

What is the place of recently approved T cell-targeted and B cell-targeted therapies in the treatment of rheumatoid arthritis? Lessons from global clinical trials. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

B cell depletion: a novel therapy for autoimmune diabetes? [2021]

12. Japan pubmed.ncbi.nlm.nih.gov

Induction of thyroid remission using rituximab in a patient with type 3 autoimmune polyglandular syndrome including Graves' disease and type 1 diabetes mellitus: a case report. [2018]