Study of Antithymocyte Globulin for Treatment of New-onset T1DM (START)

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00515099
First received: August 10, 2007
Last updated: March 25, 2014
Last verified: March 2014
Results First Received: February 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: New-onset Type 1 Diabetes Mellitus
Interventions: Drug: Antithymocyte globulin
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
This study planned a 30-month subject enrollment (e.g. accrual) period which was extended to 40-months in an effort to achieve the planned sample size. Subject enrollment closed on June 30, 2011 after 88% of the targeted number of study participants was enrolled.

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.

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.

Participant Flow:   Overall Study
    Antithymocyte Globulin     Placebo  
STARTED     38     20  
COMPLETED     36     19  
NOT COMPLETED     2     1  
Lost to Follow-up                 0                 1  
Withdrawal by Subject                 1                 0  
IRB Recommendation                 1                 0  



  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.
Intent-to-treat

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Total Total of all reporting groups

Baseline Measures
    Antithymocyte Globulin     Placebo     Total  
Number of Participants  
[units: participants]
  38     20     58  
Age  
[units: years]
Mean ± Standard Deviation
  19.4  ± 6.6     20.5  ± 7.1     19.8  ± 6.7  
Age, Customized  
[units: participants]
     
12-17 Years     19     10     29  
18-35 Years     19     10     29  
Gender  
[units: participants]
     
Female     14     9     23  
Male     24     11     35  
Region of Enrollment  
[units: participants]
     
United States     38     20     58  



  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), Month 12 ]

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), Month 12 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   Insulin Use in Units Per Kilogram Body Weight Per Day   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Proportion of Subjects Who Are Exogenous-Insulin-Free   [ Time Frame: Months 12, 18, and 24; possibly up to 60 months ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Major Hypoglycemic Events Occurring Since Treatment Randomization   [ Time Frame: Baseline through Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

6.  Secondary:   2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT)   [ Time Frame: Month 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Hemoglobin A1c   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Changes in Mean C-peptide Area Under the Curve ( AUC ) Results in Response to Standardized 2-hour and 4- Hour MMTTs Over Time   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame Start of study through October 4, 2012 (data cut for primary endpoint results)
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.

Other Adverse Events
    Antithymocyte Globulin     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     38/38     20/20  
Blood and lymphatic system disorders      
Leukopenia † 1    
# participants affected / at risk     14/38 (36.84%)     0/20 (0.00%)  
# events     20     0  
Lymphadenopathy † 1    
# participants affected / at risk     1/38 (2.63%)     2/20 (10.00%)  
# events     1     2  
Lymphopenia † 1    
# participants affected / at risk     38/38 (100.00%)     0/20 (0.00%)  
# events     47     0  
Neutropenia † 1    
# participants affected / at risk     9/38 (23.68%)     2/20 (10.00%)  
# events     10     4  
Thrombocytopenia † 1    
# participants affected / at risk     5/38 (13.16%)     0/20 (0.00%)  
# events     5     0  
Cardiac disorders      
Bradycardia † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Ear and labyrinth disorders      
Ear pain † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Middle ear effusion † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     2  
Eye disorders      
Eye irritation † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Ocular hyperaemia † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     3     0  
Visual impairment † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     3/38 (7.89%)     1/20 (5.00%)  
# events     3     1  
Abdominal pain lower † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Abdominal pain upper † 1    
# participants affected / at risk     3/38 (7.89%)     1/20 (5.00%)  
# events     3     1  
Constipation † 1    
# participants affected / at risk     4/38 (10.53%)     0/20 (0.00%)  
# events     4     0  
Diarrhoea † 1    
# participants affected / at risk     5/38 (13.16%)     3/20 (15.00%)  
# events     5     3  
Dyspepsia † 1    
# participants affected / at risk     2/38 (5.26%)     3/20 (15.00%)  
# events     2     3  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Nausea † 1    
# participants affected / at risk     8/38 (21.05%)     5/20 (25.00%)  
# events     9     7  
Oral disorder † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     4     0  
Toothache † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Vomiting † 1    
# participants affected / at risk     3/38 (7.89%)     3/20 (15.00%)  
# events     4     3  
General disorders      
Catheter site pain † 1    
# participants affected / at risk     4/38 (10.53%)     1/20 (5.00%)  
# events     4     1  
Chest discomfort † 1    
# participants affected / at risk     3/38 (7.89%)     1/20 (5.00%)  
# events     3     1  
Chest pain † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     2     1  
Face oedema † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Fatigue † 1    
# participants affected / at risk     3/38 (7.89%)     4/20 (20.00%)  
# events     4     5  
Influenza like illness † 1    
# participants affected / at risk     4/38 (10.53%)     3/20 (15.00%)  
# events     5     3  
Infusion site pain † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Infusion site swelling † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Injection site discolouration † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Injection site hypertrophy † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Malaise † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     2     1  
Pain † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     2     1  
Pyrexia † 1    
# participants affected / at risk     6/38 (15.79%)     1/20 (5.00%)  
# events     6     1  
Hepatobiliary disorders      
Hyperbilirubinaemia † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     3     0  
Immune system disorders      
Cytokine release syndrome † 1    
# participants affected / at risk     36/38 (94.74%)     0/20 (0.00%)  
# events     36     0  
Seasonal allergy † 1    
# participants affected / at risk     7/38 (18.42%)     2/20 (10.00%)  
# events     8     2  
Serum sickness † 1    
# participants affected / at risk     36/38 (94.74%)     0/20 (0.00%)  
# events     38     0  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     4     0  
Ear infection † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Eye infection † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     2  
Gastroenteritis † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Influenza † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     3     0  
Nasopharyngitis † 1    
# participants affected / at risk     5/38 (13.16%)     1/20 (5.00%)  
# events     5     1  
Oral herpes † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Otitis media † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Pharyngitis † 1    
# participants affected / at risk     2/38 (5.26%)     2/20 (10.00%)  
# events     2     2  
Pharyngitis streptococcal † 1    
# participants affected / at risk     2/38 (5.26%)     2/20 (10.00%)  
# events     4     2  
Pneumonia † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Sinusitis † 1    
# participants affected / at risk     3/38 (7.89%)     1/20 (5.00%)  
# events     4     1  
Upper respiratory tract infection † 1    
# participants affected / at risk     14/38 (36.84%)     6/20 (30.00%)  
# events     28     14  
Viral infection † 1    
# participants affected / at risk     5/38 (13.16%)     3/20 (15.00%)  
# events     10     3  
Injury, poisoning and procedural complications      
Arthropod bite † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Contusion † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Excoriation † 1    
# participants affected / at risk     4/38 (10.53%)     0/20 (0.00%)  
# events     5     0  
Fibula fracture † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Foot fracture † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Hand fracture † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Joint sprain † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Sunburn † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     3     1  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     3     0  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     4     0  
CD4 lymphocytes decreased † 1    
# participants affected / at risk     37/38 (97.37%)     0/20 (0.00%)  
# events     37     0  
Haptoglobin increased † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Weight decreased † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Metabolism and nutrition disorders      
Hyperglycaemia † 1    
# participants affected / at risk     7/38 (18.42%)     0/20 (0.00%)  
# events     8     0  
Hypoglycaemia † 1    
# participants affected / at risk     31/38 (81.58%)     16/20 (80.00%)  
# events     466     152  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     4/38 (10.53%)     3/20 (15.00%)  
# events     4     4  
Back pain † 1    
# participants affected / at risk     2/38 (5.26%)     5/20 (25.00%)  
# events     3     6  
Muscle spasms † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     2     1  
Musculoskeletal pain † 1    
# participants affected / at risk     1/38 (2.63%)     3/20 (15.00%)  
# events     1     3  
Myalgia † 1    
# participants affected / at risk     4/38 (10.53%)     2/20 (10.00%)  
# events     4     3  
Pain in extremity † 1    
# participants affected / at risk     2/38 (5.26%)     2/20 (10.00%)  
# events     3     2  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     3/38 (7.89%)     2/20 (10.00%)  
# events     3     2  
Dysaesthesia † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Headache † 1    
# participants affected / at risk     17/38 (44.74%)     10/20 (50.00%)  
# events     23     15  
Lethargy † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Migraine † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Somnolence † 1    
# participants affected / at risk     0/38 (0.00%)     2/20 (10.00%)  
# events     0     3  
Pregnancy, puerperium and perinatal conditions      
Pregnancy † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Psychiatric disorders      
Agitation † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Anxiety † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Attention deficit/hyperactivity disorder † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Depression † 1    
# participants affected / at risk     2/38 (5.26%)     2/20 (10.00%)  
# events     2     2  
Restlessness † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Renal and urinary disorders      
Proteinuria † 1    
# participants affected / at risk     0/38 (0.00%)     2/20 (10.00%)  
# events     0     2  
Reproductive system and breast disorders      
Dysmenorrhoea † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Ovarian cyst † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     3     0  
Respiratory, thoracic and mediastinal disorders      
Asthma † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Cough † 1    
# participants affected / at risk     8/38 (21.05%)     3/20 (15.00%)  
# events     10     4  
Epistaxis † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Nasal congestion † 1    
# participants affected / at risk     1/38 (2.63%)     2/20 (10.00%)  
# events     1     3  
Oropharyngeal pain † 1    
# participants affected / at risk     9/38 (23.68%)     5/20 (25.00%)  
# events     13     6  
Pharyngeal erythema † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Productive cough † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Rhinitis allergic † 1    
# participants affected / at risk     2/38 (5.26%)     1/20 (5.00%)  
# events     4     1  
Rhinorrhoea † 1    
# participants affected / at risk     1/38 (2.63%)     3/20 (15.00%)  
# events     1     3  
Sinus congestion † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     3     0  
Tonsillar hypertrophy † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Skin and subcutaneous tissue disorders      
Acne † 1    
# participants affected / at risk     7/38 (18.42%)     0/20 (0.00%)  
# events     8     0  
Blister † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Dermatitis contact † 1    
# participants affected / at risk     2/38 (5.26%)     3/20 (15.00%)  
# events     2     3  
Eczema † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     1  
Ingrowing nail † 1    
# participants affected / at risk     2/38 (5.26%)     0/20 (0.00%)  
# events     2     0  
Lipoatrophy † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     2  
Lipohypertrophy † 1    
# participants affected / at risk     0/38 (0.00%)     2/20 (10.00%)  
# events     0     3  
Pruritus † 1    
# participants affected / at risk     4/38 (10.53%)     3/20 (15.00%)  
# events     4     4  
Rash † 1    
# participants affected / at risk     7/38 (18.42%)     2/20 (10.00%)  
# events     8     3  
Rash papular † 1    
# participants affected / at risk     3/38 (7.89%)     0/20 (0.00%)  
# events     3     0  
Rash pruritic † 1    
# participants affected / at risk     1/38 (2.63%)     1/20 (5.00%)  
# events     1     5  
Urticaria † 1    
# participants affected / at risk     2/38 (5.26%)     2/20 (10.00%)  
# events     2     2  
Vascular disorders      
Flushing † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Hot flush † 1    
# participants affected / at risk     0/38 (0.00%)     1/20 (5.00%)  
# events     0     1  
Hypotension † 1    
# participants affected / at risk     0/38 (0.00%)     3/20 (15.00%)  
# events     0     3  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.1



  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
Enrollment for this trial was closed at 58 participants and did not meet the planned sample size of 66 participants due to slow accrual.


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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: Associate Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00515099     History of Changes
Other Study ID Numbers: DAIT ITN028AI
Study First Received: August 10, 2007
Results First Received: February 10, 2014
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board