- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03929601
Rituximab-pvvr and Abatacept vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes (TN25)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Ariana Rojas
- Phone Number: 813-974-6827
- Email: ariana.rojas@epi.usf.edu
Study Contact Backup
- Name: Melissa Parker
- Phone Number: 813-396-9378
- Email: melissa.parker@epi.usf.edu
Study Locations
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Victoria
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Melbourne, Victoria, Australia, 3050
- Recruiting
- Walter and Eliza Hall Institute of Medical Research
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Contact:
- Felicity Healy
- Phone Number: 9342-7063
- Email: felicity.healy@mh.org.au
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Principal Investigator:
- John Wentworth, MD
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California
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Palo Alto, California, United States, 94304
- Recruiting
- Stanford University
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Contact:
- Trudy Esrey
- Phone Number: 650-498-4450
- Email: tesrey@stanford.edu
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Principal Investigator:
- Priya Pahalad, MD
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San Francisco, California, United States, 94158
- Recruiting
- University of California San Francisco
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Principal Investigator:
- Stephen Gitelman, MD
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Contact:
- Rebecca Wesch
- Phone Number: 415-476-5356
- Email: rebecca.wesch@ucsf.edu
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Colorado
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Aurora, Colorado, United States, 80045
- Recruiting
- Barbara Davis Center for Childhood Diabetes
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Principal Investigator:
- Peter Gottlieb, MD
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Contact:
- Alison Altomari
- Phone Number: 303-724-6774
- Email: ALISON.ALTOMARI@UCDENVER.EDU
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Connecticut
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New Haven, Connecticut, United States, 06520
- Recruiting
- Yale University
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Contact:
- Marcia DeSousa
- Phone Number: 203-737-4805
- Email: marcia.desousa@yale.edu
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Principal Investigator:
- Jennifer Sherr, MD
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Florida
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Gainesville, Florida, United States, 32610
- Recruiting
- University of Florida
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Contact:
- Jennifer Hosford
- Phone Number: 352-294-5759
- Email: jennifer.hosford@medicine.ufl.edu
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Contact:
- Danielle Poulton
- Phone Number: 352-294-5761
- Email: Danielle.Poulton@medicine.ufl.edu
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Principal Investigator:
- Michael J Haller, MD
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Indiana
-
Indianapolis, Indiana, United States, 46202
- Recruiting
- Indiana University - Riley Hospital for Children
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Principal Investigator:
- Linda DiMeglio, MD
-
Contact:
- Maria Spall
- Phone Number: 317-278-8879
- Email: malnicho@iu.edu
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Kansas
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Kansas City, Kansas, United States, 64114
- Recruiting
- The Children's Mercy Hospital
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Principal Investigator:
- Wayne Moore, MD
-
Contact:
- Heather Harding
- Phone Number: 816-960-8985
- Email: hrharding@cmh.edu
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New York
-
New York, New York, United States, 10032
- Recruiting
- Columbia University
-
Principal Investigator:
- Robin Goland, MD
-
Contact:
- Kaisha Mofford
- Phone Number: 212-851-5364
- Email: km3870@cumc.columbia.edu
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- University of Pittsburg
-
Contact:
- Kelli DeLallo
- Phone Number: 412-692-5210
- Email: kelli.delallo@chp.edu
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Principal Investigator:
- Ingrid Libman, MD
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South Dakota
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Sioux Falls, South Dakota, United States, 57105
- Recruiting
- Sanford Children's Specialty Clinic
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Contact:
- Staci Schwingler
- Phone Number: 605-312-6977
- Email: Staci.Schwingler@SanfordHealth.org
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Principal Investigator:
- Kurt Griffin, MD, PhD
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Tennessee
-
Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt Eskind Diabetes Center
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Contact:
- Brenna Hammel
- Phone Number: 615-337-9597
- Email: brenna.hammel@vumc.org
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Principal Investigator:
- William Russell, MD
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Texas
-
Dallas, Texas, United States, 75390
- Recruiting
- University of Texas Southwestern
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Contact:
- Michelle Murphy
- Phone Number: 214-456-9238
- Email: michelle.murphy@utsouthwestern.edu
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Principal Investigator:
- Perrin White, MD
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Contact:
- Jamie Girard
- Phone Number: 469-744-9289
- Email: jamie.girard@utsouthwestern.edu
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Washington
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Seattle, Washington, United States, 98101
- Recruiting
- Benaroya Research Institute
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Principal Investigator:
- Sandra Lord, MD
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Contact:
- Natalie Clary
- Phone Number: 206-342-6963
- Email: nclary@benaroyaresearch.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- Up to date, including eligible boosters as indicated for COVID-19 with an authorized non-live COVID-19 vaccination at least two weeks prior to randomization.
- 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 subjects 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. Any remaining vaccinations should be given and continue per the schedule at least 6 months after rituximab-pvvr is administered.
Exclusion Criteria:
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
- Bilirubin ≥ 1.5 times upper limit of normal
- 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 clinical trial.
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Rituximab-pvvr followed by Abatacept
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). |
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 a 3-8 hour period, at a dose of 375mg/m2 on four visits each one week apart.
Other Names:
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).
Other Names:
|
Placebo Comparator: Rituximab-pvvr followed by Placebo
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. |
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 a 3-8 hour period, at a dose of 375mg/m2 on four visits each one week apart.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
C-Peptide Response to 2-hr MMTT at 24 months post-randomization
Time Frame: 48-months from Day 0
|
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.
|
48-months from Day 0
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
C-peptide AUC Means
Time Frame: Day 0 and every 6 months to trial end (up to 4 years)
|
C-peptide AUC Mean at 0, 6, 12, 18, 24, 30, 36, 42 and 48 months using the ANCOVA model.
|
Day 0 and every 6 months to trial end (up to 4 years)
|
Analysis of changes in immune responses to known diabetes antigens and a neoantigen over time by treatment group
Time Frame: Day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36
|
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.
|
Day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Stephen Gitelman, MD, Type 1 Diabetes TrialNet
- Study Director: Kevan Herold, MD, Type 1 Diabetes TrialNet Chairman
- Study Chair: Daniel Moore, MD, Type 1 Diabetes TrialNet
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Rituximab
- Abatacept
Other Study ID Numbers
- Rituximab-pvvr and Abatacept
- UC4DK117009 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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