Study Stopped
Manufacturer discontinued production of Amevive®: business decision.
Inducing Remission in Type 1 Diabetes With Alefacept
T1DAL
Inducing Remission in New Onset Type 1 Diabetes Mellitus With Alefacept (Amevive®)
1 other identifier
interventional
49
1 country
15
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2011
Typical duration for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2009
CompletedFirst Posted
Study publicly available on registry
August 25, 2009
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2014
CompletedResults Posted
Study results publicly available
January 7, 2015
CompletedJuly 6, 2017
June 1, 2017
2 years
August 22, 2009
December 19, 2014
June 12, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.
Baseline (pre-treatment initiation), Week 52
Secondary Outcomes (5)
4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
Baseline (Pre-treatment initiation), Week 52, and Week 104
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
Baseline (Pre-treatment initiation), Week 52, and Week 104
Insulin Use in Units Per Kilogram Body Weight Per Day
Baseline (Pre-treatment initiation), Week 52, and Week 104
Major Hypoglycemic Events Occurring From Randomization
Baseline to Week 52 and Week 52 to Week 104
Hemoglobin A1c
Baseline (Pre-treatment initiation), Week 52, and Week 104
Study Arms (2)
Alefacept
EXPERIMENTALSubjects 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.
Placebo
PLACEBO COMPARATORSubjects 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.
Interventions
Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
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.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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:
- White blood count \<4000/μL or \>14,000/μL;
- CD4+ count below the lower limit of normal;
- Platelet count \<150,000 /μL; or
- Hemoglobin \<10 g/dL.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
University of Arizona
Tucson, Arizona, 85724, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
University of California - San Francisco
San Francisco, California, 94143, United States
Barbara Davis Center for Childhood Diabetes - University of Colorado
Aurora, Colorado, 80045, United States
Emory University
Atlanta, Georgia, 30322, United States
Indiana University
Indianapolis, Indiana, 46202, United States
University of Iowa Hospital & Clinics
Iowa City, Iowa, 52242, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Creighton University
Omaha, Nebraska, 68131, United States
University of North Carolina
Durham, North Carolina, 27713, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101, United States
Related Publications (4)
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.
PMID: 24622404BACKGROUNDRigby 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.
PMID: 24622414RESULTRigby 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.
PMID: 26193635RESULTBoyle 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.
PMID: 27208317DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Enrollment ended early with 49 subjects (instead of the planned 66) as a result of the decision, unrelated to safety reasons, made by Astellas Pharma US, Inc. to discontinue manufacturing Amevive® (alefacept).
Results Point of Contact
- Title
- Director, Clinical Research Operations Program
- Organization
- DAIT/NIAID
Study Officials
- PRINCIPAL INVESTIGATOR
Mark R Rigby, MD, PhD
Indiana University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 22, 2009
First Posted
August 25, 2009
Study Start
March 1, 2011
Primary Completion
March 1, 2013
Study Completion
April 1, 2014
Last Updated
July 6, 2017
Results First Posted
January 7, 2015
Record last verified: 2017-06
Data Sharing
- IPD Sharing
- Will share
Participant level data access and additional relevant materials are available 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) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.