This is a randomized, double-masked, 2-arm pilot study to monitor the safety of human insulin B-chain (IBC) peptide (BB-IND 8884) in subjects with type 1 diabetes. Secondary objectives include: To analyze the metabolic effects of incomplete Freund’s adjuvant (IFA) enhanced human insulin B-chain (IBC) injection. To analyze the immune effects of the IFA enhanced autoantigen injection on humoral antibody responses (GAD65Ab, IAA, AI2Ab and heterophile antibodies) vs. vehicle control injection. To analyze the effect of IBC-VS01 vs. VS02 injection on the measurement of C-peptide responses following a mixed meal tolerance test at serial time points compared to baseline. Arm 1 of the study will be given IBC-VS01 (insulin B-chain peptide) 2mg in Montanide ISA51-incomplete Freund’s adjuvant in a 50/50 (w/w) emulsion, total volume 1 mL given by IM injection. Arm 2 will be given a buffer solution (VS02) in Montanide ISA51-incomplete Freund’s adjuvant in a 50/50 (w/w) emulsion, total volume 1 mL given by IM injection. The primary outcome is safety. Safety will be assessed by clinical endpoints including adverse events, local reactions, routine physical exams, insulin dose, and laboratory tests. Secondary outcomes include C-peptide levels in response to mixed meal tolerance test, HbA1c, GAD65Ab, IAA, IA2Ab, GAD65Ab isotypes, CD4-CD8- Vα24JαQ+, T cells’ secretion of IL-4 and INFγ.

Plan to Share IPD: Yes Plan Description: Data access is provided to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) portal.

instance of dataset

available with registration

Orban

National Institute of Allergy and Infectious Diseases (NIAID)

Biological: IBC-VS01 IBC-VS01 Biological: IBC-VS01 placebo IBC-VS01 placebo

registration required

Insulin-dependent Diabetes Mellitus Diabetes Mellitus

Tihamer Orban, MD

Joslin Diabetes Center

Principal Investigator

Evaluation of a Diabetes Vaccine in Newly Diagnosed Diabetics

12

Clinical endpoints including adverse events, local reactions, routine physical exams, insulin dose, and laboratory tests [ Time Frame: Throughout study ]

C-peptide levels in response to mixed meal tolerance test [ Time Frame: Throughout study ] HbA1c, GAD65Ab, IAA, IA2Ab, GAD65Ab isotypes [ Time Frame: Throughout study ] CD4- and CD8- Va24JaQ+ [ Time Frame: Throughout study ] T cells' secretion of IL-4 and Interferon (IFN)-gamma [ Time Frame: Throughout study ]

NC

Inclusion Criteria: Diagnosed with type 1 diabetes mellitus within 3 months prior to study entry Positive for IAA, GAD65, or IA2 antibodies OR positive for GAD65 or IA2 antibodies after 2 weeks of starting insulin treatment Exclusion Criteria: History of treatment with any oral hypoglycemic agent for more than 3 months Ongoing use of medications known to influence glucose tolerance History of immunosuppressive or steroid therapy for more than 3 months within the 2 years prior to study entry Severe active liver, heart, kidney, or immunodeficiency disease that may limit life expectancy or may require immunosuppression during the study Prior complications related to routine vaccinations Prior participation in a trial for prevention of type 1 diabetes mellitus. Individuals who are known to have been in the placebo arm of a completed prevention trial are not excluded. Any condition that may interfere with a participant's ability to comply with the study Pregnancy or planned pregnancy within the time frame of the study

2007-03-01

Autoantigen Vaccination in Human Type 1 Newly Diagnosed Diabetes Mellitus

Experimental: IBC-VS01 vaccine IBC-VS01 vaccine is administered twice. Intervention: Biological: IBC-VS01 Placebo Comparator: Control Group IBC-VS01 placebo is administered twice Intervention: Biological: IBC-VS01 placebo

Insulin dependent diabetes mellitus (also called type 1 diabetes mellitus or T1DM) is caused by the destruction of insulin-producing cells in the pancreas. People with T1DM do not produce enough insulin, which is necessary for proper regulation of blood sugar levels. T1DM is an autoimmune disease. An autoimmune disease is a disease in which the body's immune system attacks the body itself. In addition to regulating blood sugar, insulin may have the ability to protect cells in the pancreas from attack by the immune system. This study will evaluate whether an insulin-based vaccine can protect cells from autoimmune destruction. Study hypothesis: IFA-enhanced human insulin B-chain vaccination will lead to the arrest or slowing of the ongoing autoimmunity, and this will result in an appreciable difference in functioning B cell mass compared to the placebo treated group by the end of the study.

The vaccine in this study, IBC-VSO1, is a synthetic, metabolically inactive form of insulin designed to prevent pancreatic beta-cell destruction. It does not cause fluctuations in blood sugar. This study will evaluate whether the vaccine protects against autoimmune attack at the onset of T1DM, before pancreas function has deteriorated. This experimental treatment must occur early because 60% to 85% of beta-cells are already destroyed by the time of T1DM diagnosis. If beta-cell destruction can be halted, a prolonged remission period after diagnosis may occur, with a subsequent delay in diabetes-related complications. Participants must have been diagnosed with T1DM for no more than 3 months at the time of enrollment in this study. Participants will be randomly assigned to either a vaccine group or a control group. Participants in the vaccine group will receive one injection of IBC-VS01; participants in the control group will receive a placebo. Participants will then be monitored for 2 years. Participants will have ten follow-up visits, which will include blood tests for immunological and genetic analysis. Throughout the study, metabolic tests will also be performed to measure the remaining capacity of self insulin production of the body.

Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment

United States

2003-03-01

ITN TrialShare