Inducing Remission in Type 1 Diabetes With Alefacept

NCT ID: NCT00965458

Last Updated: 2017-07-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-04-30

Brief Summary

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 is a multi-center prospective, placebo-controlled, double-blind and randomized trial to investigate the ability of alefacept to protect residual beta cells from ongoing autoimmune destruction in adolescents and young adults with newly diagnosed Type 1 Diabetes Mellitus (T1DM).

Detailed Description

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.

Conditions

New-onset Type 1 Diabetes Mellitus

Study Design

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

Study Groups

Alefacept

Subjects in this group receive weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Group Type: EXPERIMENTAL

Alefacept

Intervention Type: BIOLOGICAL

Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Placebo

Subjects in this group received weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Interventions

Alefacept

Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Intervention Type: BIOLOGICAL

Placebo

Weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.

Intervention Type: DRUG

Other Intervention Names

Amevive®; Inactive drug (pharmacologically)

Eligibility Criteria

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.

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

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark R Rigby, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

University of Arizona

Tucson, Arizona, United States

Children's Hospital of Los Angeles

Los Angeles, California, United States

University of California - San Francisco

San Francisco, California, United States

Barbara Davis Center for Childhood Diabetes - University of Colorado

Aurora, Colorado, United States

Emory University

Atlanta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa Hospital & Clinics

Iowa City, Iowa, United States

University of Maryland

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Creighton University

Omaha, Nebraska, United States

University of North Carolina

Durham, North Carolina, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States

Countries

United States

References

Herold KC. Restoring immune balance in type 1 diabetes. Lancet Diabetes Endocrinol. 2013 Dec;1(4):261-3. doi: 10.1016/S2213-8587(13)70123-2. Epub 2013 Sep 23. No abstract available.

Reference Type: BACKGROUND

PMID: 24622404 (View on PubMed)

Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Patel CM, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Moran A, Russell WE, Pinckney A, Keyes-Elstein L, Howell M, Aggarwal S, Lim N, Phippard D, Nepom GT, McNamara J, Ehlers MR; T1DAL Study Team. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):284-94. doi: 10.1016/S2213-8587(13)70111-6. Epub 2013 Sep 23.

Reference Type: RESULT

PMID: 24622414 (View on PubMed)

Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015 Aug 3;125(8):3285-96. doi: 10.1172/JCI81722. Epub 2015 Jul 20.

Reference Type: RESULT

PMID: 26193635 (View on PubMed)

Boyle KD, Keyes-Elstein L, Ehlers MR, McNamara J, Rigby MR, Gitelman SE, Weiner LJ, Much KL, Herold KC. Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal in Type 1 Diabetes. Diabetes Care. 2016 Jun;39(6):e76-8. doi: 10.2337/dc15-2077. Epub 2016 Apr 13. No abstract available.

Reference Type: DERIVED

PMID: 27208317 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

TrialShare study ID is T1DAL ITN045AI.

View Document

Document Type: Study Protocol

TrialShare study ID is T1DAL ITN045AI.

View Document

Document Type: Study overview, -data and reports, -schedule of assessments, -study design, -original article & abstracts et al.

TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

https://www.niddk.nih.gov/

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) website

http://www.immunetolerance.org

Immune Tolerance Network (ITN) website

http://jdrf.org/about-jdrf/

Juvenile Diabetes Research Foundation (JDRF) website

Other Identifiers

DAIT ITN045AI

Identifier Type: -

Identifier Source: org_study_id