Beta Cell Rescue in New Onset Type 1 Diabetes With Efalizumab

NCT ID: NCT00737763

Last Updated: 2014-05-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2009-11-30

Brief Summary

In this single-center therapeutic study, we will study the ability of efalizumab to protect remaining beta cells in teenagers and young adults who have been newly diagnosed with type 1 diabetes mellitus. Efalizumab is a monoclonal antibody which prevents the activation of antigen specific T lymphocytes to sites of inflammation. Efalizumab was approved by the FDA in 2003 for the treatment of psoriasis. It has been proven to be safe, well tolerated and effective in targeting T cell mediated disorders like those seen in autoimmunity.

Detailed Description

Since there is data that shows that early intervention can prevent further destruction of insulin producing beta cells, the patients who will be enrolled in this study will have been diagnosed with Type 1 diabetes within 6 weeks of enrolling and starting therapy. Patients who meet the screening criteria will be randomized at a 2 to 1 ratio to either get weekly subcutaneous injections of efalizumab for 26 weeks versus a placebo injection. The researchers and patients will be blinded to the treatment group assignment. All patients will be followed for two years.

The primary endpoint for this study will be the difference from baseline in the body's ability to respond to a Mixed Meal Tolerance Test at 12 months after enrollment. The Mixed Meal Tolerance test will help test the production of insulin by the pancreas. By comparing the results of these tests between the treated group and the placebo group, we hope to be able to show preservation of beta cell function in the group treated with efalizumab.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A

This group will receive weekly efalizumab injections for 6 months

Group Type: EXPERIMENTAL

efalizumab

Intervention Type: DRUG

Enrollees randomized to efalizumab will receive the first dose of 0.7mg/kg subcutaneously given at enrollment, and 1.0 mg/kg subcutaneously weekly for 26 weeks self or family-administered after injection training. This is the FDA-approved initial and subsequent doses of efalizumab used for psoriasis treatment

B

This group will receive placebo injections for 6 months

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Enrollees receiving placebo will be given a subcutaneous injection of equal volume and appearance to treatment on the same schedule.

Interventions

efalizumab

Enrollees randomized to efalizumab will receive the first dose of 0.7mg/kg subcutaneously given at enrollment, and 1.0 mg/kg subcutaneously weekly for 26 weeks self or family-administered after injection training. This is the FDA-approved initial and subsequent doses of efalizumab used for psoriasis treatment

Intervention Type: DRUG

placebo

Enrollees receiving placebo will be given a subcutaneous injection of equal volume and appearance to treatment on the same schedule.

Intervention Type: DRUG

Other Intervention Names

Raptiva; none applicable

Eligibility Criteria

Inclusion Criteria

• Males or females 12-35 years old, no preference nor discrimination will be made based on ethnicity.
• Recent diagnosis of Type 1Diabetes Mellitus, participant can be enrolled in the trial within 6 weeks of diagnosis.
• Positive for at least one diabetes autoantibody. Insulin autoantibody positivity will only be used as a selection criterion if insulin has not been used in at least the preceding 10 days.
• Willingness to provide written informed consent (either the subject or the subject's legally authorized representative)
• Have routine diabetic care under an endocrinologist and ability to follow study protocol for the duration of the 2-year study.
• Although no preference or discrimination will be made based on ethnicity or gender, participants (and family and/or guardians when applicable) must demonstrate comprehension of the trial, including its obligations and potential risks.
• If a female of childbearing potential, a negative pregnancy test and commitment to the use of two forms of effective contraception or abstinence for the duration of the study are necessary.
• If a non-sterile male, commitment to the use of two forms of effective contraception (birth control) for the duration of the study is necessary.

Exclusion Criteria

• Severe allergic allergy or anaphylaxis to human monoclonal antibodies
• Hospital admission for cardiac disease, stroke, or pulmonary disease within the past year
• History of substance abuse within last 5 years
• History of ongoing uncontrolled bacterial, viral, or fungal or atypical mycobacterium infections
• History of opportunistic infections
• Diagnosis with hepatic cirrhosis regardless of cause or severity
• Diagnosis, history, or laboratory evidence of Hepatitis B or C infection
• Hepatic enzymes 2 > times the upper limit of normal
• History of active or treatment for tuberculosis or skin test positive
• History of malignancy over the past 5 years
• Recent initiation or change in treatment regimen of beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, or lithium in the past month
• Seropositivity for human immunodeficiency virus (HIV)
• Serologic or clinical evidence of recent or acute infection with Epstein-Barr Virus or Cytomegalovirus
• Females who are pregnant, lactating, or planning on pregnancy during the 2 year study period
• Progressive hearing loss
• History of organ or bone marrow transplantation, sickle cell disease, cystic fibrosis, autoimmune anemia, seizures, autoimmune thrombocytopenia, leuko/lymphopenia, vasculitis, other autoimmune disease.
• Current use of immunosuppressive medications
• Plan or requirement of receiving new immunization of any type within the first 12 months of the study, or booster or completion vaccines with live or live-attenuated vaccines
• Any condition that, in judgment of the investigator, could jeopardize the subject-safety following exposure to the drug.
• Participation in another simultaneous medical investigation or trial

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Mark Rigby

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark R Rigby, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University, Children's Healthcare of Atlanta

Eric Felner, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Healthcare of Atlanta, Emory University

Sol Jacobs, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Christian Larsen, MD, DPhil

Role: PRINCIPAL_INVESTIGATOR

Emory University

Other Identifiers

BRiTE Trial for T1DM

Identifier Type: OTHER

Identifier Source: secondary_id

IRB0007365

Identifier Type: -

Identifier Source: org_study_id