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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00279305




Registration number
NCT00279305
Ethics application status
Date submitted
17/01/2006
Date registered
19/01/2006
Date last updated
6/05/2020

Titles & IDs
Public title
Rituximab in New Onset Type 1 Diabetes
Scientific title
Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects
Secondary ID [1] 0 0
U01DK061055
Secondary ID [2] 0 0
TN05 Ritux
Universal Trial Number (UTN)
Trial acronym
TN05
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 - Placebo Comparator

Experimental: Rituximab Intravenous Infusion - Participants will receive active rituximab (anti-CD20 monoclonal antibody) as an intravenous infusion, with 4 administrations at weeks 0, 1, 2, and 3 at a dose of 375mg/m2

Placebo comparator: Placebo Intravenous Infusion - Participants will receive placebo given as an intravenous infusion with 4 administrations at weeks 0, 1, 2, and 3.


Treatment: Drugs: Placebo Comparator
Placebo intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4-hour Mixed Meal Tolerance Test (MMTT) Administered at 1 Year
Timepoint [1] 0 0
When all participants complete the 1 year visit

Eligibility
Key inclusion criteria
* Between the ages of 8 and 45 years
* Within 3 months of diagnosis of type 1 diabetes
* Have presence of at least one diabetes-related autoantibody
* Must have stimulated C-peptide levels of at least 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) within one month of randomization
* If female with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing while participating in the study
* Have not received an immunization for at least one month
* Must be willing to comply with intensive diabetes management
* Must weigh at least 25 kg at study entry
Minimum age
8 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Are immunodeficient or have clinically significant chronic lymphopenia
* Have an active infection or positive purified protein derivative (PPD) test result
* Currently pregnant or lactating; or anticipate becoming pregnant.
* Require chronic use of steroids
* Have current or past HIV, hepatitis B, or hepatitis C infection
* Have any complicating medical issues that interfere with study conduct or cause increased risk
* Have a history of malignancies
* Currently using non-insulin pharmaceuticals that effect glycemic control
* Currently participating in another type 1 diabetes treatment study

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2009
Sample size
Target
Accrual to date
Final
87
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Walter and Eliza Hall Institute of Medical Research - Victoria
Recruitment postcode(s) [1] 0 0
- Victoria
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Italy
State/province [12] 0 0
Milan

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 Institute of Allergy and Infectious Diseases (NIAID)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
American Diabetes Association
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Juvenile Diabetes Research Foundation
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these beta cells, the body cannot maintain proper blood glucose levels in response to daily activities such as eating or exercise. With fewer insulin producing cells blood glucose increases, causing hunger, thirst, and unexplained weight loss. By the time these symptoms develop, 80-90% of a person's beta cells have already been destroyed. However, this also means that between 10-20% of these cells remain that continue to produce insulin.

Scientists have learned that two types of immune cells, B cells and T cells, are involved in causing type 1 diabetes. T cells are responsible for attacking and destroying the beta cells that make insulin. Although they don't attack insulin producing cells, B cells may be what trigger the T cells to attack.

This study will investigate the use of rituximab to see if it can help lower the number of immune B cells thereby preventing the destruction of any remaining insulin producing beta cells that remain at diagnosis. Rituximab is approved by the Food and Drug Administration (FDA) for the treatment of a condition called B-lymphocyte lymphoma. Its effects on the immune system are well understood through its use in organ transplantation. Research has shown that rituximab might be helpful in treating other conditions caused by T cells and B cells, including type 1 diabetes. The goal of this study is to find out if rituximab can preserve residual insulin secretion and prevent further beta cell destruction in type 1 diabetes.
Trial website
https://clinicaltrials.gov/study/NCT00279305
Trial related presentations / publications
Pescovitz MD. The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant. 2004 Feb;8(1):9-21. doi: 10.1046/j.1397-3142.2003.00135.x.
Noorchashm H, Noorchashm N, Kern J, Rostami SY, Barker CF, Naji A. B-cells are required for the initiation of insulitis and sialitis in nonobese diabetic mice. Diabetes. 1997 Jun;46(6):941-6. doi: 10.2337/diab.46.6.941.
Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, Jankovic M, Pierani P, De Stefano P, Bonora MR, Locatelli F. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003 May 15;101(10):3857-61. doi: 10.1182/blood-2002-11-3547. Epub 2003 Jan 16.
Binstadt BA, Caldas AM, Turvey SE, Stone KD, Weinstein HJ, Jackson J, Fuhlbrigge RC, Sundel RP. Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr. 2003 Nov;143(5):598-604. doi: 10.1067/s0022-3476(03)00382-2. Erratum In: J Pediatr. 2004 Apr;144(4):558.
Edwards JC, Leandro MJ, Cambridge G. B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun. 2005;8:175-92. doi: 10.1159/000082103.
Sidner RA, Book BK, Agarwal A, Bearden CM, Vieira CA, Pescovitz MD. In vivo human B-cell subset recovery after in vivo depletion with rituximab, anti-human CD20 monoclonal antibody. Hum Antibodies. 2004;13(3):55-62.
Bearden CM, Agarwal A, Book BK, Vieira CA, Sidner RA, Ochs HD, Young M, Pescovitz MD. Rituximab inhibits the in vivo primary and secondary antibody response to a neoantigen, bacteriophage phiX174. Am J Transplant. 2005 Jan;5(1):50-7. doi: 10.1111/j.1600-6143.2003.00646.x.
Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. doi: 10.1056/NEJMoa032534.
Serreze DV, Silveira PA. The role of B lymphocytes as key antigen-presenting cells in the development of T cell-mediated autoimmune type 1 diabetes. Curr Dir Autoimmun. 2003;6:212-27. doi: 10.1159/000066863. No abstract available.
Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, Raskin P, Rodriguez H, Schatz DA, Wherrett D, Wilson DM, Lachin JM, Skyler JS; Type 1 Diabetes TrialNet Anti-CD20 Study Group. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009 Nov 26;361(22):2143-52. doi: 10.1056/NEJMoa0904452.
Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, Moran A, Raskin P, Rodriguez H, Schatz DA, Wherrett DK, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Anti-CD20 Study Group. B-lymphocyte depletion with rituximab and beta-cell function: two-year results. Diabetes Care. 2014 Feb;37(2):453-9. doi: 10.2337/dc13-0626. Epub 2013 Sep 11.
Public notes

Contacts
Principal investigator
Name 0 0
Carla Greenbaum, 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00279305