Inducing Remission in Type 1 Diabetes With Alefacept

T1DM is an autoimmune disease that can emerge suddenly, causing dependence on insulin for
life. This means that the immune system (the part of your body that helps fight infections)
mistakenly attacks the cells in the pancreas that produce insulin (beta cells). As beta cells
are destroyed, one's ability to produce insulin is decreased. Insulin helps keep blood
glucose (sugar) levels normal.

For a period right after diagnosis, the pancreas is still able to make small amounts of
insulin. Individuals with diabetes who have the ability to produce some of their own insulin
may be able to achieve better blood sugar control than people who produce no insulin at all.
Based on previous research, doctors think that giving medicines to affect the immune system
soon after diagnosis may stop, delay, or decrease the destruction of beta cells, resulting in
better glucose control. This can help prevent secondary complications of diabetes down the
road.

Research has improved the outlook for T1DM over the last decade. Doctors are investigating,
for example, how to save insulin-producing cells and extend the honeymoon period as long as
possible.

Despite progress towards understanding the science behind T1DM, there remains a significant
need to investigate alternative approaches to this disease in order to bring about long-term
remission. For this reason, scientists are working hard to develop new treatments that can be
given soon after diagnosis to preserve the remaining beta cells.

Currently there is no cure for T1DM; however, with new investigational medications and
innovative clinical research studies, such as T1DAL, a new approach towards managing T1DM may
be on the horizon.

Enrollees will receive weekly intramuscular injections of alefacept or placebo for two 12
week periods, with a 12-week pause between treatment intervals. This schedule or drug dosing
may be altered due to the needs of the subject or at the discretion of the physician
investigator.

Inclusion Criteria:

- Recent diagnosis (within 100 days of enrollment) of T1DM

- Positive for at least one diabetes autoantibody (Glutamate decarboxylase
[GAD-65GAD65], IA2, ZnT8, ICA and Insulin, if obtained within 10 days of the onset of
exogenous insulin therapy)

- Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed-meal tolerance test
(MMTT)

- Willingness to provide written informed consent (either the subject or the subject's
legally authorized representative).

Exclusion Criteria:

- Severe reaction or anaphylaxis to human monoclonal antibodies

- History of malignancy or significant cardiovascular disease (including history of
myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or
abnormal stress test)

- History of recent or ongoing uncontrolled bacterial, viral, fungal, or other
opportunistic infections

- Evidence of infection with hepatitis B virus (HBV) as defined by hepatitis B surface
antigen, HBsAg; hepatitis C virus (HCV) defined by anti-HCV antibodies; human
immunodeficiency virus (HIV); or toxoplasmosis

- Positive tuberculin skin test (PPD)

- Clinically active infection with Epstein-Barr virus (EBV)-EBV viral load ≥ 10,000
copies per 10^6 PBMCs; cytomegalovirus (CMV) -CMV viral load ≥10,000 copies per mL
whole blood; or tuberculosis (TB)

- Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2 times
the upper limit of normal

- Prior or current treatment that is known to cause a significant, ongoing change in the
course of T1DM or immunologic status, including high-dose inhaled, extensive topical
or systemic glucocorticoids

- Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides,
thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin

- Current use of any medication known to influence glucose tolerance (e.g., atypical
antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics,
β-adrenergic blockers, niacin)

- Any of the following hematologic abnormalities, confirmed by repeat tests at least 1
week apart:

1. White blood count <4000/μL or >14,000/μL;

2. CD4+ count below the lower limit of normal;

3. Platelet count <150,000 /μL; or

4. Hemoglobin <10 g/dL.

- Females who are pregnant, lactating, or planning on pregnancy during the 2-year study
period

- History of bone marrow transplantation, or autoimmune disease associated with
lymphopenia

- Any medical condition that in the opinion of the principal investigator would
interfere with safe completion of the trial

- Prior participation in a clinical trial that could potentially affect T1DM or
immunologic status

- Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated
intranasal influenza vaccine, bacillus Calmette-Guérin, and smallpox) in the 6 weeks
before enrollment

- Participation in an investigational clinical trial within the last six weeks.