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Trial record 1 of 1 for:    t1dal AND alefacept
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Inducing Remission in Type 1 Diabetes With Alefacept (T1DAL)

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00965458
First received: August 22, 2009
Last updated: August 12, 2014
Last verified: August 2014

August 22, 2009
August 12, 2014
March 2011
March 2013   (final data collection date for primary outcome measure)
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (pre-treatment initiation), Week 52 ] [ Designated as safety issue: No ]
Difference in c-peptide production following a mixed meal tolerance test of subjects receiving alefacept, compared to those receiving placebo, at 12 months following enrollment. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00965458 on ClinicalTrials.gov Archive Site
  • 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (Pre-treatment initiation), Week 52, and Week 104 ] [ Designated as safety issue: No ]
  • 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline (Pre-treatment initiation), Week 52, and Week 104 ] [ Designated as safety issue: No ]
  • Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Major Hypoglycemic Events Occurring From Randomization [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Hemoglobin A1c [ Time Frame: Week 52, Week 104 ] [ Designated as safety issue: No ]
  • Rate of Injection Reactions; Defined as Fever, Chills, Headache, Nausea, Vomiting, and Injection-site Pain in Participants Receiving Alefacept or Placebo. [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Rate of Hypersensitivity Reactions; Defined as Signs and Symptoms of Anaphylaxis, Wheezing, Dyspnea, Urticaria, and Hypotension in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Rate of Evidence of Infection with Epstein-Barr virus (EBV), Cytomegalovirus (CMV), or Tuberculosis (TB) in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • Frequency and Severity of all Adverse Events (AEs) in Participants Receiving Alefacept or Placebo [ Time Frame: Initiation of treatment through duration of study participation ] [ Designated as safety issue: Yes ]
  • •Compared to baseline, change in C-peptide AUC from enrollment to AUC at 3, 6, 18 and 24 months. This change will be compared between subjects receiving alefacept and those receiving placebo. [ Time Frame: 3, 6, 18, 24mos ] [ Designated as safety issue: No ]
  • Absolute C-peptide AUC at enrollment, compared between alefacept and placebo groups. [ Time Frame: 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  • • Absolute peak C-peptide levels with MMTT at enrollment and 3, 6, 12, 18 and 24 months, comparing between alefacept and placebo groups. [ Time Frame: enrollment and 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  • • Change from baseline and absolute insulin use from enrollment to 3, 6, 12, 18 and 24 months, compared between alefacept and placebo groups. [ Time Frame: enrollment, 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  • • Change from baseline and absolute glycemic control (reflected by HgbA1C) from enrollment to 3, 6, 12, 18 and 24 months, compared between alefacept and placebo groups. [ Time Frame: enrollment, 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
  • • Change from baseline and absolute numbers of positive diabetes auto-antibodies from enrollment to 3, 6, 12, 18 and 24 months, compared between alefacept and placebo groups. [ Time Frame: enrollment, 3, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Inducing Remission in Type 1 Diabetes With Alefacept
Inducing Remission in New Onset Type 1 Diabetes Mellitus With Alefacept (Amevive®)

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
New-onset Type 1 Diabetes Mellitus
  • Biological: Alefacept
    Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
    Other Name: Amevive®
  • Drug: 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.
    Other Name: Inactive drug (pharmacologically)
  • Experimental: 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.
    Intervention: Biological: Alefacept
  • Placebo Comparator: 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.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
April 2014
March 2013   (final data collection date for primary outcome measure)

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
Both
12 Years to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00965458
DAIT ITN045AI
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Principal Investigator: Mark R Rigby, MD, PhD Indiana University
National Institute of Allergy and Infectious Diseases (NIAID)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP