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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

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]

U01DK061055

Secondary ID [2]

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

Condition category

Condition code

Metabolic and Endocrine

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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]

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?

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

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Walter and Eliza Hall Institute of Medical Research - Victoria

Recruitment postcode(s) [1]

- Victoria

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Colorado

Country [3]

United States of America

State/province [3]

Florida

Country [4]

United States of America

State/province [4]

Indiana

Country [5]

United States of America

State/province [5]

Massachusetts

Country [6]

United States of America

State/province [6]

Minnesota

Country [7]

United States of America

State/province [7]

New York

Country [8]

United States of America

State/province [8]

Pennsylvania

Country [9]

United States of America

State/province [9]

Texas

Country [10]

United States of America

State/province [10]

Washington

Country [11]

Canada

State/province [11]

Ontario

Country [12]

Italy

State/province [12]

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]

Government body

Name [1]

National Institute of Allergy and Infectious Diseases (NIAID)

Address [1]

Country [1]

Other collaborator category [2]

Government body

Name [2]

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Address [2]

Country [2]

Other collaborator category [3]

Other

Name [3]

American Diabetes Association

Address [3]

Country [3]

Other collaborator category [4]

Other

Name [4]

Juvenile Diabetes Research Foundation

Address [4]

Country [4]

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

Carla Greenbaum, MD

Address

Type 1 Diabetes TrialNet

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn05-anticd20/?query=tn05

When will data be available (start and end dates)?

Available to whom?

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: https://repository.niddk.nih.gov/studies/tn05-anticd20/?query=tn05

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Type	Citations or Other Details
Journal	Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Be... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT00279305

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Registering a new trial?

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