Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"

National Institutes of Health (NIH)

Status and phase: Completed; Phase 2

Conditions: Impaired Glucose Tolerance; Autoantibody Positive; High Risk; Non-diabetic Relatives at Risk for Type 1 Diabetes

Treatments: Drug: Placebo infusion; Drug: Teplizumab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01030861

TrialNet - tep (IND)

UC4DK106993 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the "pre-diabetic" state and thereby prevent or delay the onset of type 1 diabetes.

Full description

The study plans to enroll approximately 71 subjects between the ages of 8-45 years, over 2-3 years. The study is projected to last between 4-6 years, depending upon rate of enrollment and number of subjects who develop diabetes.

The main study objective is to determine whether intervention with teplizumab will prevent or delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and other mechanistic outcomes will be assessed during the study.

Enrollment: 76 patients

Sex: All

Ages: 8 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Between ages of 8-45 years
• Have a relative with type 1 diabetes
• If first degree relative must be 8-45 years old (brother, sister, parent, offspring)
• If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle, grandchild, cousin)
• Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit [fasting blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on OGTT greater than or equal to 200 mg/dL]
• Presence of at least two confirmed diabetes autoantibodies

Exclusion criteria

• type 1 diabetes previously diagnosed or detected at screening [fasting glucose greater or equal to 126 mg/dL or 2 hour glucose greater or equal to 200 mg/dL]

• abnormalities in blood counts, liver enzymes, international normalised ratio (INR),

• positive purified protein derivative (PPD) test

  • vaccination with live virus within 6 weeks of randomization

• evidence of acute infection based on laboratory testing or clinical evidence

• serological evidence of past current or past HIV , hepatitis B, or hepatitis C infection

• Be currently pregnant or lactating

• Prior treatment with study drug

• Prior treatment with other monoclonal antibody in past one year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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76 participants in 2 patient groups, including a placebo group

teplizumab

Active Comparator group

Description:

Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.

Treatment:

Drug: Teplizumab

Placebo infusion

Placebo Comparator group

Description:

Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period.

Treatment:

Drug: Placebo infusion