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Type 1 Diabetes MellitusPhase 2TN25NCT03929601

Rituximab-pvvr and Abatacept vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes

A Phase 2 study testing Rituximab-pvvr, Abatacept and Sterile Sodium Chloride in people with Type 1 Diabetes Mellitus, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 19 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The study is a two-arm, multicenter, double-blinded clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in new onset T1D. Read more about this study

Who is it for?
Ages 8 to 45 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Rituximab-pvvr, Abatacept and Sterile Sodium Chloride
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
74 participants
Where
19 sitesin 2 countries
Study dates
30 Oct 2023to 31 Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age ≥ 8 and ≤ 45 years old at time of signing informed consent.
  • Fulfill the ADA criteria for diagnosis of T1D within 100 days of randomization.
  • Must be willing to provide informed consent or assent with a parent or legal guardian providing informed consent if \< 18 years of age.
  • 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
  • Must have stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days after the diagnosis of diabetes.
  • Enrollees must be willing to comply with intensive diabetes management.
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  • Body weight must be ≥ 20.0 kg for study agent administration.
  • Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR negative and may not have had signs or symptoms of a CMV and/or EBV compatible illness prior to randomization.
  • Female participants with reproductive potential must have a negative pregnancy test at screening and be willing to avoid pregnancy for the duration of treatment and until 3 months after the last dose of Abatacept. Female participants with reproductive potential who are sexually active will be instructed to use a highly effective contraceptive method until one year after the last dose of rituximab-pvvr.
  • Male participants of reproductive age must use an adequate contraceptive method for the duration of rituximab-pvvr treatment and 12 months following the last dose of rituximab-pvvr.
  • The following additional inclusion criteria regarding vaccines must be met:
  • More than 4 weeks from immunization with a live viral vaccine
  • Be up to date on all recommended vaccinations based on age of subject*
  • Receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
  • Willingness to forgo vaccines (other than killed influenza) during the 6 months after the rituximab-pvvr treatment period
  • Participants must be willing to practice public health prevention measures such as social distancing, masking, and good hand hygiene, and/or receive therapeutics such as monoclonal antibodies and antivirals as directed by the study and recommended by local health authorities to prevent SARS-Cov-2 infection.
  • Willing to wear a continuous glucose monitoring device for a minimum of 10 days every 6 months
  • Adult participants must be fully immunized. Pediatric subjects who have not completed their primary vaccination schedule must receive all vaccinations allowable per local public health immunization guidelines for their current age prior to study drug delivery. HPV vaccine may be initiated and/or series completion delayed until after completion of study drug in both adult and pediatric participants. Any remaining vaccinations should be given and continue per the schedule at least 6 months after rituximab-pvvr is administered. For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine(s) as indicated by country-specific guidelines at least 2 weeks prior to randomization.

Who cannot join

  • One or more screening laboratory values as stated:
  • Leukocytes \<3,000/μL
  • Neutrophils \<1,500/μL
  • Lymphocytes \<800/μL
  • Platelets \<100,000/μL
  • Hemoglobin \<6.2 mmol/L (10.0 g/dL)
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  • Potassium \>5.5 mmol/L or \<3.0 mmol/L
  • Sodium \>150 mmol/L or \<130 mmol/L
  • AST or ALT ≥ 2.5 times the upper limits of normal
  • Total bilirubin ≥ 1.5 times upper limit of normal, except in the case of Gilbert's disease
  • History of immune deficiency
  • Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening visit.
  • Chronic active infection other than localized skin infections.
  • Have active signs or symptoms of acute infection at the time of randomization.
  • Have IgG and/or IgM levels below the normal reference ranges.
  • Positive PPD, interferon gamma release assay (IGRA) or history of previous treatment for TB.
  • Vaccination with a live virus within 4 weeks prior to initiating study treatment.
  • 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).
  • Laboratory evidence of current or past HIV or Hepatitis B or active Hepatitis C infection.
  • Be currently pregnant, lactating or anticipate pregnancy within 14 weeks of the last study drug administration (Visit 15).
  • Chronic use of oral or inhaled steroids or other immunosuppressive agents.
  • Known and untreated hypothyroidism or active Graves' disease at randomization.
  • History of malignancy.
  • Prior treatment with active study agent from a previous T1D clinical trial.*
  • Have had previous clinical use of Tzield (Teplizumab) not part of a T1D treatment study.
  • Any laboratory abnormality or condition that, in the opinion of the investigator, would interfere with the study conduct or the safety of the participant.
  • Study drug exposure may be reviewed by the TrialNet Eligibility and Events Committee and determination will be made as to whether subjects can be considered eligible for this study based on agent, length of time since exposure, duration of treatment, durability of effect, and potential for lingering immunomodulation.

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

United States17 sites

  • Barbara Davis Center for Childhood Diabetes

    Aurora, Colorado, 80045

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • University of Florida

    Gainesville, Florida, 32610

  • Indiana University - Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • The Children's Mercy Hospital

    Kansas City, Kansas, 64114

  • University of Miami

    Maimi, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt Eskind Diabetes Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • Columbia University

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868

  • Stanford University

    Palo Alto, California, 94304

  • University of Pittsburg

    Pittsburgh, Pennsylvania, 15224

  • University of California San Francisco

    San Francisco, California, 94158

  • Benaroya Research Institute

    Seattle, Washington, 98101

  • Sanford Children's Specialty Clinic

    Sioux Falls, South Dakota, 57105

Other trials in United States

Australia2 sites

  • Walter and Eliza Hall Institute of Medical Research

    Melbourne, Victoria, 3050

  • Queensland Children's Hospital

    South Brisbane, Queensland, 4101

Other trials in Australia

About this study

The study is a two-arm, multicenter, double-blinded clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in new onset T1D. The primary objective is to test whether the C-peptide response to a 2-hour mixed meal tolerance test, will be improved in participants with new onset T1D who are treated with Abatacept after Rituximab-pvvr compared to those treated with Rituximab-pvvr and placebo 24 months after enrollment.

Read the detailed description

This is a two-arm, double-blind, multicenter clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in individuals with new onset T1D to determine whether rituximab-pvvr followed by abatacept results in an improvement in the AUC C-Peptide during a MMTT compared to Rituximab-pvvr alone at 24 months. Additional aims will compare the safety, tolerability in the two treatment arms as well as other clinical metabolic measures: exogenous insulin use, hemoglobin A1c, time in range from continuous glucose monitors, and severe hypoglycemia. Exploratory studies will assess changes in immune markers.

Being tested
Rituximab-pvvr, Abatacept, Sterile Sodium Chloride
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rituximab-pvvrDrug

    Also called Ruxience

    All participants will receive Rituximab-pvvr dosing from Week 1 to Week 4 of the trial. 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.

  • AbataceptDrug

    Also called Orencia

    Participants in the active drug arm will receive initial Abatacept dosing at Week 16 of trial. Abatacept will be given by a subcutaneous (SC) formulation weekly for 20 months, and dosing be will determined according to 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).

  • Sterile Sodium ChlorideDrug

    Also called 0.9% Sodium Chloride Water for Injection

    Participants in the placebo arm will receive initial placebo injection at Week 16 of trial. Saline Placebo will be given by a subcutaneous (SC) formulation weekly for 20 months, and dosing volume be will determined according to weight to match active comparator: Up to 25 kg: 0.4 mL; 25 to <50 kg receive 0.7 mL and > 50 kg receive 1.0 mL.

Study groups in NCT03929601
Study groupRoleWhat they receive
Rituximab-pvvr followed by AbataceptActive comparatorRituximab-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).
Receives: Drug: Rituximab-pvvr; Drug: Abatacept
Rituximab-pvvr followed by PlaceboPlacebo comparatorRituximab-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.
Receives: Drug: Rituximab-pvvr; Drug: Sterile Sodium Chloride

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    The primary objective is to test whether the C-peptide response to a 2-hour mixed meal tolerance test, will be improved in participants with new onset T1D who are treated with Abatacept after Rituximab compared to those participants treated with Rituximab and placebo 24 months after enrollment.

    Measured: 48-months from Day 0

Secondary outcomes (2)

  1. C-peptide AUC Means

    C-peptide AUC Mean at 0, 6, 12, 18, 24, 30, 36, 42 and 48 months using the ANCOVA model.

    Measured: Day 0 and every 6 months to trial end (up to 4 years)

  2. Analysis of changes in immune responses to known diabetes antigens and a neoantigen over time by treatment group

    Analysis of changes in immune responses to known diabetes antigens and a neoantigen. The investigators will compare the effects of drug treatments on the titers of autoantibodies: anti-insulin, anti-GAD65, anti-IA-2, anti-ZnT8. The investigators will also compare the effects of drug treatments on the response to Keyhole Limpet Hemocyanin (KLH) for which standardized immunological responses have been characterized.

    Measured: Day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2019
  2. Study start30 Oct 2023
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
This protocol will enroll 74 participants who will be treated with a course of rituximab-pvvr (weekly infusion for 4 weeks), followed by treatment with abatacept or placebo starting at 4 months after initial rituximab-pvvr treatment and continuing to month 24. The abatacept/placebo treatment will be self-administered by participants (or their families/guardians, where most appropriate, particularly with pediatric participants) weekly for 20 months. 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/placebo 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).
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03929601
Sponsor's protocol ID
Rituximab-pvvr and Abatacept
Other IDs
UC4DK117009
Acronym
TN25
Status last verified
Aug 2026
First submitted
16 May 2018
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

    PubMed 39735417

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab-pvvr, Abatacept and Sterile Sodium Chloride in people with Type 1 Diabetes Mellitus, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

C-Peptide Response to 2-hr MMTT at 24 months post-randomization (time frame: 48-months from Day 0). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03929601, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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