Inducing Remission in Type 1 Diabetes With Alefacept

Condition(s) targeted: Diabetes Mellitus, Type 1

Intervention: alefacept (Drug); placebo (saline) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Mark R Rigby, MD, PhD, Principal Investigator, Affiliation: Emory University

Overall contact:
Stephanie Meisner, RN, BSN, Phone: (404) 785-6453, Email: stephanie.meisner@choa.org

The purpose of this trial is to test whether a drug called alefacept will slow or halt destruction of the beta cells in the pancreas. If the destruction of the beta cells is stopped the patients might be able to produce insulin on their own longer which could stop or slow the progression of their type 1 diabetes.

This proposal is for a multi-center prospective, placebo-controlled, double-blind and randomized, controlled trial to investigate the ability of alefacept to protect residual beta cells in adolescents and young adults with newly diagnosed Type 1 diabetes mellitus from ongoing autoimmune destruction.

Official title: Inducing Remission in New Onset Type 1 Diabetes Mellitus With Alefacept (Amevive®)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Mixed-meal tolerance test (MMTT) stimulated 2-hour C-peptide area under the curve (AUC)

Secondary outcome:

MMTT-stimulated peak and 4-hour C-peptide AUC

MMTT-stimulated 2-hour C-peptide AUC assessed

Insulin use in units per kilogram body weight per day

Major hypoglycemic events occurring from randomization

HbA1C levels

Rate of injection reactions; defined as fever, chills, headache, nausea, vomiting, and injection-site pain in participants receiving alefacept or placebo.

Rate of hypersensitivity reactions; defined as signs and symptoms of anaphylaxis, wheezing, dyspnea, urticaria, and hypotension in participants receiving alefacept or placebo.

Rate of evidence of infection with Epstein-Barr virus (EBV), Cytomegalovirus (CMV), or Tuberculosis (TB) in participants receiving alefacept or placebo.

Frequency and severity of all AEs in participants receiving alefacept or placebo

Detailed description: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease that can emerge suddenly causing dependence on insulin for life. This means that your 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, your ability to produce insulin is decreased. Insulin helps keep blood glucose (sugar) levels normal.

For a period right after diagnosis, your pancreas is still able to make small amounts of insulin. People 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.

Doctors are investigating how to save the insulin producing cells and extend the honeymoon period as long as possible. But research has dramatically improved the outlook for type 1 diabetes over the last decade.

Despite progress towards understanding the science behind T1DM, there still remains a significant need to investigate alternative approaches to type 1 diabetes in order to bring about long-term remission in this condition. For this reason, scientists are working hard to develop new treatments that can be given soon after diagnosis to preserve the remaining beta cells.

At the moment there is no cure. But with new investigational mediations and innovative clinical research studies, such as T1DAL, a new approach towards managing type 1 diabetes 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. This schedule or drug dosing may be altered due to the needs of the subject or at the discretion of the physician investigator.

Minimum age: 12 Years. Maximum age: 35 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Recent diagnosis of T1DM within 100 days of enrollment.

- 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 HBV (as defined by hepatitis B surface antigen, HBsAg),

HCV (anti-HCV antibodies), HIV or toxoplasmosis.

- Positive tuberculin skin test (PPD).

- Clinically active infection with EBV, CMV, or tuberculosis; or EBV viral load ≥

10,000 copies per 106 PBMCs or CMV viral load ≥10,000 copies per mL whole blood.

- 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.

Stephanie Meisner, RN, BSN, Phone: (404) 785-6453, Email: stephanie.meisner@choa.org

University of Arizona, Tuscon, Arizona 85724, United States; Recruiting
Doris Ross, Phone: 520-626-8112, Email: djross@email.arizona.edu
Kurt Griffin, MD, PhD, Principal Investigator

Children's Hospital of Los Angeles, Los Angeles, California 90027, United States; Recruiting
Meredith Bock, Phone: 323-361-6082, Email: mbock@chla.usc.edu
Roshanek Monzavi, MD, Principal Investigator

University of California - San Francisco, San Francisco, California 94143, United States; Recruiting
Kathleen Fraser, Phone: 415-353-9084, Email: kfraser@diabetes.ucsf.edu
Stephen Gitelman, MD, Principal Investigator

Barbara Davis Center for Childhood Diabetes - University of Colorado, Aurora, Colorado 80045, United States; Recruiting
Rebecca Wagner, Phone: 303-724-7502, Email: Rebecca.Wagner@ucdenver.ed
Peter Gottlieb, MD, Principal Investigator

University of Miami Hospital and Clinics, Miami, Florida 33136, United States; Recruiting
Della Matheson, Phone: 305-243-3781, Email: dmatheso@med.miami.edu
Jennifer Marks, MD, Principal Investigator

Emory University, Atlanta, Georgia 30322, United States; Recruiting
Gregory Smallwood, Phone: 404-727-9831, Email: gasmall@emory.edu
Stephanie Meisner, Phone: 404-785-6453, Email: stephanie.meisner@choa.org
Eric I Felner, MD, Principal Investigator
Sol Jacobs, MD, Sub-Investigator

Indiana University, Indianapolis, Indiana 46202, United States; Recruiting
LeeAnn Ford, Phone: 317-948-8879, Email: lford@iupui.edu
Stephanie Stein, Phone: 317-944-3889, Email: sestein@iupui.edu
Linda DiMeglio, MD, MPH, Principal Investigator
Mark Rigby, MD, PhD, FAAP, FCCM, Principal Investigator

University of Iowa Hospital & Clinics, Iowa City, Iowa 52242, United States; Recruiting
Joanne Cabbage, Phone: 319-353-6070, Email: joanne-cabbage@uiowa.edu
Sarah Salamati, Phone: 319-356-3954, Email: sarah_salamati@uiowa.edu
Eva Tsalikian, Principal Investigator

University of Maryland, Baltimore, Maryland 21201, United States; Recruiting
Debra Counts, MD, Phone: 410-328-3412, Email: dcounts@peds.umaryland.edu
Debra Counts, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Sarah Dean, Phone: 617-643-6739, Email: sdean3@partners.org
Nicole A Sherry, MD, Principal Investigator

University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Carrie Gibson, Phone: 612-626-5206, Email: gibso002@umn.edu
M. Anne Street, Phone: 612-625-9709, Email: stree065@umn.edu
Antoinette Moran, MD, Principal Investigator

Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, United States; Recruiting
SueEllen Weigel, RN, Phone: 816-234-3975, Email: sweigel@cmh.edu
Wayne Moore, MD, Principal Investigator

Creighton University, Omaha, Nebraska 68131, United States; Recruiting
Kayla Zebrowski, Phone: 402-280-4319, Email: kaylaschmit@creighton.edu
Shayla Addison, Phone: 402-280-4319, Email: shaylaaddison@creighton.edu
Marc Rebdell, MD, Principal Investigator

University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Barbara Johnson, Phone: 585-276-3513, Email: barbara_johnson@urmc.rochester.edu
Nicholas Jospe, MD, Principal Investigator

University of North Carolina, Durham, North Carolina 27713, United States; Recruiting
Gail Fuller, CCRC, Phone: 919-484-0931, Ext: 272, Email: gail_fuller@med.unc.edu
Jean Dostou, MD, Principal Investigator
Michelle Duclos, MD, Sub-Investigator

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Tammy Calvano, Phone: 267-426-3908, Email: calvanot@email.chop.edu
Olena Kucheruk, Phone: 267-426-3909, Email: kucheruk@email.chop.edu
Steven Willi, MD, Principal Investigator

Vanderbilt University, Nashville, Tennessee 37232, United States; Not yet recruiting
Faith Brendle, Phone: 615-936-8638, Email: faith.brendle@vanderbilt.edu
Margo Black, Phone: 615-936-8638, Email: margo.black@vanderbilt.edu
William Russell, MD, Principal Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Renee Davis, BSN, RN, Phone: 214-648-8858, Email: renee.davis@utsouthwestern.edu
Jamie Arthur, Phone: 214-648-4830, Email: jamie.arthur@utsouthwestern.edu
Philip Raskin, MD, Principal Investigator

Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, United States; Recruiting
Christine Webber, Phone: 206-342-6936, Email: cwebber@benaroyaresearch.org
Diabetes Research Program, Phone: 800-888-4187, Email: diabetes@benaroyaresearch.org
Carla Greenbaum, MD, Principal Investigator

Starting date: March 2011
Last updated: November 16, 2011