Inducing Remission in Type 1 Diabetes With Alefacept (T1DAL)

This study has been completed.
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00965458
First received: August 22, 2009
Last updated: January 6, 2015
Last verified: January 2015
Results First Received: December 19, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: New-onset Type 1 Diabetes Mellitus
Interventions: Biological: Alefacept
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited during an approximate 84-week accrual period. Initially 66 subjects were planned; however, enrollment ended with 49 subjects as a result of the decision, unrelated to safety reasons, made by Astellas Pharma US, Inc. to discontinue manufacturing Amevive (alefacept).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects ages 12 to 35 years who were first diagnosed with type 1 diabetes mellitus (T1DM) within 100 days of enrollment. Subjects were randomly assigned in a 2 to 1 (2:1) ratio to either the alefacept or placebo group.

Reporting Groups
  Description
Alefacept

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

Alefacept: 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.

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.


Participant Flow:   Overall Study
    Alefacept     Placebo  
STARTED     33     16  
COMPLETED     31     12  
NOT COMPLETED     2     4  
Adverse Event                 1                 0  
Lost to Follow-up                 1                 3  
Withdrawal by Subject                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Alefacept

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

Alefacept: 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.

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.

Total Total of all reporting groups

Baseline Measures
    Alefacept     Placebo     Total  
Number of Participants  
[units: participants]
  33     16     49  
Age  
[units: participants]
     
<=18 years     17     8     25  
Between 18 and 65 years     16     8     24  
>=65 years     0     0     0  
Age  
[units: years]
Mean (Standard Deviation)
  20.3  (6.4)     19.5  (6.2)     20.0  (6.3)  
Gender  
[units: participants]
     
Female     16     4     20  
Male     17     12     29  
Region of Enrollment  
[units: participants]
     
United States     33     16     49  
2-Hour C-peptide Area Under the Curve Result in Response to Standardized Mixed Meal Tolerance Test [1]
[units: pmol/mL]
Mean (Standard Deviation)
  0.85  (0.42)     0.64  (0.22)     0.78  (0.38)  
[1] 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 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 post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease.



  Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   04/2015   Safety Issue:   No

3.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   04/2015   Safety Issue:   No

4.  Secondary:   Insulin Use in Units Per Kilogram Body Weight Per Day   [ Time Frame: Week 52, Week 104 ]
Results not yet reported.   Anticipated Reporting Date:   04/2015   Safety Issue:   No

5.  Secondary:   Major Hypoglycemic Events Occurring From Randomization   [ Time Frame: Week 52 and 104 ]
Results not yet reported.   Anticipated Reporting Date:   04/2015   Safety Issue:   Yes

6.  Secondary:   Hemoglobin A1c   [ Time Frame: Week 52, Week 104 ]
Results not yet reported.   Anticipated Reporting Date:   04/2015   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Failure to meet the primary endpoint might have resulted, partly, from the trial's reduced power. The planned enrollment of 66 individuals was curtailed at 49 patients following voluntary withdrawal of alefacept by the manufacturer.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications of Results:
Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00965458     History of Changes
Other Study ID Numbers: DAIT ITN045AI
Study First Received: August 22, 2009
Results First Received: December 19, 2014
Last Updated: January 6, 2015
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board