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

Running, not enrolling · Phase 2 · Has a placebo group

Conditions studied: Type 1 Diabetes Mellitus

In brief

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.

Key facts

Study ID

NCT03929601

Run by

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

People needed

74

Starts

2023-10-30

Expected to finish

2029-03-31

Last updated by the study team

2026-02-19

Who can join

Age: 8 and older, up to 45. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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)
• 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.

Where it is running

• Childrens Hospital of Orange County — Orange, California, United States
• Stanford University — Palo Alto, California, United States
• University of California San Francisco — San Francisco, California, United States
• Barbara Davis Center for Childhood Diabetes — Aurora, Colorado, United States
• Yale University — New Haven, Connecticut, United States
• University of Florida — Gainesville, Florida, United States
• University of Miami — Maimi, Florida, United States
• Indiana University - Riley Hospital for Children — Indianapolis, Indiana, United States
• The Children's Mercy Hospital — Kansas City, Kansas, United States
• Joslin Diabetes Center — Boston, Massachusetts, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• Columbia University — New York, New York, United States
• University of Pittsburg — Pittsburgh, Pennsylvania, United States
• Sanford Children's Specialty Clinic — Sioux Falls, South Dakota, United States
• Vanderbilt Eskind Diabetes Center — Nashville, Tennessee, United States
• University of Texas Southwestern — Dallas, Texas, United States
• Benaroya Research Institute — Seattle, Washington, United States
• Queensland Children's Hospital — South Brisbane, Queensland, Australia
• Walter and Eliza Hall Institute of Medical Research — Melbourne, Victoria, Australia

Full record on ClinicalTrials.gov

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