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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03929601




Registration number
NCT03929601
Ethics application status
Date submitted
16/05/2018
Date registered
29/04/2019

Titles & IDs
Public title
Rituximab-pvvr and Abatacept Vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes
Scientific title
Rituximab-pvvr and Abatacept Vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes
Secondary ID [1] 0 0
UC4DK117009
Secondary ID [2] 0 0
Rituximab-pvvr and Abatacept
Universal Trial Number (UTN)
Trial acronym
TN25
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rituximab-pvvr
Treatment: Drugs - Abatacept
Treatment: Drugs - Sterile Sodium Chloride

Active comparator: Rituximab-pvvr followed by Abatacept - 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).

Placebo comparator: Rituximab-pvvr followed by Placebo - 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.


Treatment: Drugs: Rituximab-pvvr
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.

Treatment: Drugs: Abatacept
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).

Treatment: Drugs: Sterile Sodium Chloride
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
C-Peptide Response to 2-hr MMTT at 24 months post-randomization
Timepoint [1] 0 0
48-months from Day 0
Secondary outcome [1] 0 0
C-peptide AUC Means
Timepoint [1] 0 0
Day 0 and every 6 months to trial end (up to 4 years)
Secondary outcome [2] 0 0
Analysis of changes in immune responses to known diabetes antigens and a neoantigen over time by treatment group
Timepoint [2] 0 0
Day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36

Eligibility
Key inclusion criteria
1. Age = 8 and = 45 years old at time of signing informed consent.
2. Fulfill the ADA criteria for diagnosis of T1D within 100 days of randomization.
3. Must be willing to provide informed consent or assent with a parent or legal guardian providing informed consent if &lt; 18 years of age.
4. 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
5. 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.
6. Enrollees must be willing to comply with intensive diabetes management.
7. Body weight must be = 20.0 kg for study agent administration.
8. 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.
9. 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.
10. 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.
11. The following additional inclusion criteria regarding vaccines must be met:

1. More than 4 weeks from immunization with a live viral vaccine
2. Be up to date on all recommended vaccinations based on age of subject*
3. Receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
4. Willingness to forgo vaccines (other than killed influenza) during the 6 months after the rituximab-pvvr treatment period
12. 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.
13. 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. 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.
Minimum age
8 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. One or more screening laboratory values as stated:

1. Leukocytes &lt;3,000/µL
2. Neutrophils &lt;1,500/µL
3. Lymphocytes &lt;800/µL
4. Platelets &lt;100,000/µL
5. Hemoglobin &lt;6.2 mmol/L (10.0 g/dL)
6. Potassium &gt;5.5 mmol/L or &lt;3.0 mmol/L
7. Sodium &gt;150 mmol/L or &lt;130 mmol/L
8. AST or ALT = 2.5 times the upper limits of normal
9. Total bilirubin = 1.5 times upper limit of normal, except in the case of Gilbert's disease
2. History of immune deficiency
3. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening visit.
4. Chronic active infection other than localized skin infections.
5. Have active signs or symptoms of acute infection at the time of randomization.
6. Have IgG and/or IgM levels below the normal reference ranges.
7. Positive PPD, interferon gamma release assay (IGRA) or history of previous treatment for TB.
8. Vaccination with a live virus within 4 weeks prior to initiating study treatment.
9. 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).
10. Laboratory evidence of current or past HIV or Hepatitis B or active Hepatitis C infection.
11. Be currently pregnant, lactating or anticipate pregnancy within 14 weeks of the last study drug administration (Visit 15).
12. Chronic use of oral or inhaled steroids or other immunosuppressive agents.
13. Known and untreated hypothyroidism or active Graves' disease at randomization.
14. History of malignancy.
15. Prior treatment with active study agent from a previous T1D clinical trial.
16. Have had previous clinical use of Tzield (Teplizumab) not part of a T1D treatment study.
17. 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2029
Actual
Sample size
Target
74
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 0 0
Walter and Eliza Hall Institute of Medical Research - Melbourne
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Dakota
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institutes of Health (NIH)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stephen Gitelman, MD
Address 0 0
Type 1 Diabetes TrialNet
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ariana Rojas
Address 0 0
Country 0 0
Phone 0 0
813-974-6827
Fax 0 0
Email 0 0
ariana.rojas@epi.usf.edu
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03929601