AzTrials
AzTrials

New-onset Type 1 Diabetes MellitusPhase 2T1DALNCT00965458

Inducing Remission in Type 1 Diabetes With Alefacept

A Phase 2 study testing Alefacept in people with New-onset Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 to 35 years
Conditions the study is for
New-onset Type 1 Diabetes Mellitus
What is being tested?
Alefacept
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
49 participants
Where
15 sitesUnited States
Study dates
Mar 2011to Apr 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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).

Who cannot join

  • 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)
Show all 21Show fewer
  • 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.
  • 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.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Barbara Davis Center for Childhood Diabetes - University of Colorado

    Aurora, Colorado, 80045

  • University of Maryland

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • University of North Carolina

    Durham, North Carolina, 27713

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa Hospital & Clinics

    Iowa City, Iowa, 52242

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • Creighton University

    Omaha, Nebraska, 68131

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of California - San Francisco

    San Francisco, California, 94143

  • Benaroya Research Institute at Virginia Mason

    Seattle, Washington, 98101

  • University of Arizona

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: 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).

Read the 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.

Being tested
Alefacept, Placebo
Keywords
New-onset Type 1 Diabetes Mellitus, New-onset T1DM, New-onset T1D, Alefacept, Amevive®

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlefaceptBiological

    Also called Amevive®

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

  • PlaceboDrug

    Also called Inactive drug (pharmacologically)

    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.

Study groups in NCT00965458
Study groupRoleWhat they receive
AlefaceptExperimentalSubjects 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.
Receives: Biological: Alefacept
PlaceboPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (pre-treatment initiation), Week 52

Secondary outcomes (5)

  1. 4-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.

    Measured: Baseline (Pre-treatment initiation), Week 52, and Week 104

  2. 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.

    Measured: Baseline (Pre-treatment initiation), Week 52, and Week 104

  3. Insulin Use in Units Per Kilogram Body Weight Per Day

    The need to use insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.

    Measured: Baseline (Pre-treatment initiation), Week 52, and Week 104

  4. Major Hypoglycemic Events Occurring From Randomization

    Major hypoglycemic events are defined as a glucose concentration <55 mg/dL (grades 2-5, NCI-CTCAE version 3.0), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover.

    Measured: Baseline to Week 52 and Week 52 to Week 104

  5. Hemoglobin A1c

    Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c level of 5.6% or less is considered normal. HbA1c levels of 6.5% or higher is typical for individuals with Type 1 Diabetes Mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.

    Measured: Baseline (Pre-treatment initiation), Week 52, and Week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2009 (estimated)
  2. Study startMar 2011
  3. Primary completionMar 2013
  4. Study completionApr 2014

Why it stopped: Manufacturer discontinued production of Amevive®: business decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00965458
Sponsor's protocol ID
DAIT ITN045AI
Acronym
T1DAL
Status last verified
Jun 2017
First submitted
22 Aug 2009
Last updated
6 Jul 2017
Data monitoring committee
Yes
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 24622404

  • 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.

    PubMed 24622414

  • 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.

    PubMed 26193635

  • 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.

    PubMed 27208317

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alefacept in people with New-onset Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00965458, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2017; AzTrials last refreshed its copy on 1 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in