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

NCT03929601 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Rituximab-pvvr and AbataceptUC4DK117009
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 19

Brief 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. 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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (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.

  48-months from Day 0

Secondary Outcomes (2)

• C-peptide AUC Means

  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

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

Study Arms (2)

Rituximab-pvvr followed by Abatacept

ACTIVE COMPARATOR

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).

Drug: Rituximab-pvvr; Drug: Abatacept

Rituximab-pvvr followed by Placebo

PLACEBO COMPARATOR

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.

Drug: Rituximab-pvvr; Drug: Sterile Sodium Chloride

Interventions

Sterile Sodium Chloride DRUG

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.

Also known as: 0.9% Sodium Chloride Water for Injection

Rituximab-pvvr followed by Placebo

Rituximab-pvvr DRUG

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.

Also known as: Ruxience

Rituximab-pvvr followed by Abatacept; Rituximab-pvvr followed by Placebo

Abatacept DRUG

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).

Also known as: Orencia

Rituximab-pvvr followed by Abatacept

Eligibility Criteria

• Age: 8 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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 \&lt; 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.
• 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.

You may not qualify if:

• One or more screening laboratory values as stated:
• Leukocytes \&lt;3,000/μL
• Neutrophils \&lt;1,500/μL
• Lymphocytes \&lt;800/μL
• Platelets \&lt;100,000/μL
• Hemoglobin \&lt;6.2 mmol/L (10.0 g/dL)
• Potassium \&gt;5.5 mmol/L or \&lt;3.0 mmol/L
• Sodium \&gt;150 mmol/L or \&lt;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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• National Institutes of Health (NIH): collaborator

Study Sites (19)

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Maimi, Florida, 33136, United States

Location

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

The Children's Mercy Hospital

Kansas City, Kansas, 64114, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pittsburg

Pittsburgh, Pennsylvania, 15224, United States

Location

Sanford Children's Specialty Clinic

Sioux Falls, South Dakota, 57105, United States

Location

Vanderbilt Eskind Diabetes Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Walter and Eliza Hall Institute of Medical Research

Melbourne, Victoria, 3050, Australia

Location

Related Publications (1)

• 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.

  PMID: 39735417 DERIVED

Related Links

• Study Sponsor Website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Abatacept; Injections

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Stephen Gitelman, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

• Kevan Herold, MD

  Type 1 Diabetes TrialNet Chairman

  STUDY DIRECTOR

• Daniel Moore, MD

  Type 1 Diabetes TrialNet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is double blinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: April 29, 2019
• Study Start: October 30, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2029
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (17); AU (2)