Trial Outcomes & Findings for New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial (NCT NCT00100178)
NCT ID: NCT00100178
Last Updated: 2020-05-05
Results Overview
The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
126 participants
Primary outcome timeframe
2 years
Results posted on
2020-05-05
Participant Flow
Thirteen Clinical Centers at academic institutions recruited and enrolled 126 subjects ages 8 to 45 years with autoimmune T1D for less than 3 months.
Subjects were screened for evidence of autoantibodies and c-peptide \>0.2 pmol on a stimulated 2 hr Mixed Meal Tolerance Test to determine eligibility for the study.The MMTT must be conducted at least 21 days from the diagnosis of diabetes and no more than one month (37 days) prior to the date of randomization.
Participant milestones
| Measure |
MMF and DZB
DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.
|
MMF Alone
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
|
MMF-DZB Placebo Control
Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
31
|
42
|
|
Overall Study
COMPLETED
|
32
|
21
|
32
|
|
Overall Study
NOT COMPLETED
|
9
|
10
|
10
|
Reasons for withdrawal
| Measure |
MMF and DZB
DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.
|
MMF Alone
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
|
MMF-DZB Placebo Control
Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
6
|
5
|
|
Overall Study
Adverse Event
|
2
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
1
|
|
Overall Study
Physician Decision
|
6
|
1
|
3
|
Baseline Characteristics
New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial
Baseline characteristics by cohort
| Measure |
MMF and DZB
n=41 Participants
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years AND DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later.
|
MMF Alone
n=31 Participants
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years AND saline intravenous infusions given at baseline and two weeks later
|
MMF-DZB Placebo Control
n=42 Participants
Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.
|
Total
n=114 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
18.4 years
STANDARD_DEVIATION 9.09 • n=99 Participants
|
17.1 years
STANDARD_DEVIATION 6.71 • n=107 Participants
|
18.8 years
STANDARD_DEVIATION 10.44 • n=206 Participants
|
18.2 years
STANDARD_DEVIATION 9.01 • n=7 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
46 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
68 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: Participants who completed a 4-hour mixed meal glucose tolerance test at the two-year visit were included in the analysis
The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
Outcome measures
| Measure |
MMF and DZB
n=22 Participants
DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.
|
Placebo Control
n=20 Participants
Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
|
MMF Alone
n=18 Participants
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
|
|---|---|---|---|
|
Mean Stimulated C-peptide Area Under the Curve
|
0.28 pmol/ml
Interval 0.19 to 0.37
|
0.27 pmol/ml
Interval 0.18 to 0.37
|
0.25 pmol/ml
Interval 0.14 to 0.37
|
Adverse Events
MMF and DZB
Serious events: 15 serious events
Other events: 41 other events
Deaths: 0 deaths
MMF Alone
Serious events: 5 serious events
Other events: 31 other events
Deaths: 0 deaths
MMF-DZB Placebo Control
Serious events: 5 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MMF and DZB
n=41 participants at risk
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later .
|
MMF Alone
n=31 participants at risk
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
|
MMF-DZB Placebo Control
n=42 participants at risk
Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/41
|
3.2%
1/31 • Number of events 1
|
0.00%
0/42
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow Unspecified
|
7.3%
3/41 • Number of events 3
|
3.2%
1/31 • Number of events 1
|
2.4%
1/42 • Number of events 1
|
|
Cardiac disorders
Cardiac General - Other
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Gastrointestinal disorders
Diarrhea
|
2.4%
1/41 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
0.00%
0/42
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/41
|
0.00%
0/31
|
2.4%
1/42 • Number of events 1
|
|
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other
|
0.00%
0/41
|
3.2%
1/31 • Number of events 1
|
0.00%
0/42
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Amylase
|
0.00%
0/41
|
3.2%
1/31 • Number of events 1
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
2.4%
1/41 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
4.8%
2/42 • Number of events 2
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
2.4%
1/42 • Number of events 1
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory - Other
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory Unspecified
|
4.9%
2/41 • Number of events 2
|
0.00%
0/31
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Psychiatric disorders
Mood alteration
|
2.4%
1/41 • Number of events 2
|
3.2%
1/31 • Number of events 2
|
0.00%
0/42
|
|
Nervous system disorders
Seizure
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Eye disorders
Cataract
|
2.4%
1/41 • Number of events 2
|
0.00%
0/31
|
0.00%
0/42
|
|
Eye disorders
Ocular/Visual - Other
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
General disorders
Secondary Malignancy Unspecified
|
0.00%
0/41
|
3.2%
1/31 • Number of events 1
|
0.00%
0/42
|
|
Reproductive system and breast disorders
Sexual/Reproductive Function - Other
|
2.4%
1/41 • Number of events 1
|
0.00%
0/31
|
0.00%
0/42
|
|
Gastrointestinal disorders
Gastrointestinal- Other
|
0.00%
0/41
|
0.00%
0/31
|
2.4%
1/42 • Number of events 1
|
Other adverse events
| Measure |
MMF and DZB
n=41 participants at risk
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later .
|
MMF Alone
n=31 participants at risk
600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
|
MMF-DZB Placebo Control
n=42 participants at risk
Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.
|
|---|---|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
0.00%
0/41
|
6.5%
2/31 • Number of events 3
|
0.00%
0/42
|
|
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
14.6%
6/41 • Number of events 7
|
0.00%
0/31
|
7.1%
3/42 • Number of events 3
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow - Other
|
9.8%
4/41 • Number of events 5
|
16.1%
5/31 • Number of events 10
|
0.00%
0/42
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
12.2%
5/41 • Number of events 7
|
12.9%
4/31 • Number of events 10
|
0.00%
0/42
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow Unspecified
|
14.6%
6/41 • Number of events 9
|
22.6%
7/31 • Number of events 14
|
16.7%
7/42 • Number of events 13
|
|
Cardiac disorders
Vasovagal episode
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
0.00%
0/42
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
0.00%
0/42
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
9.8%
4/41 • Number of events 4
|
9.7%
3/31 • Number of events 4
|
0.00%
0/42
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
9.8%
4/41 • Number of events 5
|
19.4%
6/31 • Number of events 7
|
0.00%
0/42
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
26.8%
11/41 • Number of events 14
|
9.7%
3/31 • Number of events 5
|
11.9%
5/42 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
7.3%
3/41 • Number of events 4
|
12.9%
4/31 • Number of events 4
|
0.00%
0/42
|
|
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
0.00%
0/42
|
|
Gastrointestinal disorders
Dental: periodontal disease
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
0.00%
0/42
|
|
Gastrointestinal disorders
Dental: teeth
|
7.3%
3/41 • Number of events 3
|
12.9%
4/31 • Number of events 4
|
0.00%
0/42
|
|
Gastrointestinal disorders
Diarrhea
|
29.3%
12/41 • Number of events 14
|
16.1%
5/31 • Number of events 8
|
28.6%
12/42 • Number of events 13
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
0.00%
0/41
|
9.7%
3/31 • Number of events 3
|
11.9%
5/42 • Number of events 6
|
|
Gastrointestinal disorders
Nausea
|
17.1%
7/41 • Number of events 11
|
16.1%
5/31 • Number of events 5
|
14.3%
6/42 • Number of events 7
|
|
Gastrointestinal disorders
Vomiting
|
19.5%
8/41 • Number of events 11
|
22.6%
7/31 • Number of events 8
|
14.3%
6/42 • Number of events 6
|
|
Vascular disorders
Hemorrhage, pulmonary/upper respiratory
|
0.00%
0/41
|
9.7%
3/31 • Number of events 5
|
0.00%
0/42
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e
|
12.2%
5/41 • Number of events 6
|
12.9%
4/31 • Number of events 4
|
11.9%
5/42 • Number of events 6
|
|
Infections and infestations
Infection - Other
|
12.2%
5/41 • Number of events 5
|
0.00%
0/31
|
0.00%
0/42
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils
|
24.4%
10/41 • Number of events 18
|
19.4%
6/31 • Number of events 15
|
16.7%
7/42 • Number of events 8
|
|
Infections and infestations
Infection with unknown ANC
|
87.8%
36/41 • Number of events 106
|
87.1%
27/31 • Number of events 61
|
81.0%
34/42 • Number of events 94
|
|
Infections and infestations
Infection Unspecified
|
24.4%
10/41 • Number of events 23
|
6.5%
2/31 • Number of events 11
|
14.3%
6/42 • Number of events 8
|
|
Blood and lymphatic system disorders
Lymphatics - Other
|
9.8%
4/41 • Number of events 5
|
0.00%
0/31
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
0.00%
0/41
|
9.7%
3/31 • Number of events 5
|
0.00%
0/42
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
31.7%
13/41 • Number of events 24
|
29.0%
9/31 • Number of events 21
|
23.8%
10/42 • Number of events 26
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory Unspecified
|
19.5%
8/41 • Number of events 10
|
0.00%
0/31
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
7.3%
3/41 • Number of events 3
|
0.00%
0/31
|
16.7%
7/42 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other
|
19.5%
8/41 • Number of events 13
|
9.7%
3/31 • Number of events 5
|
21.4%
9/42 • Number of events 10
|
|
Nervous system disorders
Dizziness
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
0.00%
0/42
|
|
Psychiatric disorders
Mood alteration
|
0.00%
0/41
|
6.5%
2/31 • Number of events 2
|
7.1%
3/42 • Number of events 3
|
|
General disorders
Other AE Unspecified
|
12.2%
5/41 • Number of events 6
|
16.1%
5/31 • Number of events 11
|
11.9%
5/42 • Number of events 8
|
|
General disorders
Pain
|
24.4%
10/41 • Number of events 11
|
19.4%
6/31 • Number of events 18
|
19.0%
8/42 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
26.8%
11/41 • Number of events 14
|
6.5%
2/31 • Number of events 2
|
9.5%
4/42 • Number of events 5
|
|
Reproductive system and breast disorders
Irregular menses (change from baseline)
|
7.3%
3/41 • Number of events 4
|
0.00%
0/31
|
0.00%
0/42
|
|
Reproductive system and breast disorders
Sexual/Reproductive Function - Other
|
0.00%
0/41
|
0.00%
0/31
|
7.1%
3/42 • Number of events 3
|
|
General disorders
Flu-like syndrome
|
0.00%
0/41
|
0.00%
0/31
|
9.5%
4/42 • Number of events 5
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/41
|
6.5%
2/31 • Number of events 3
|
0.00%
0/42
|
Additional Information
Peter Gottleib, MD
Barbara Davis Center for Childhood Diabetes, Health Sciences Center, University of Colorado
Phone: 303-724-6714
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place