Trial Outcomes & Findings for Rituximab in New Onset Type 1 Diabetes (NCT NCT00279305)
NCT ID: NCT00279305
Last Updated: 2020-05-06
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. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
87 participants
Primary outcome timeframe
When all participants complete the 1 year visit
Results posted on
2020-05-06
Participant Flow
Participants with newly diagnosed type 1 diabetes recruited from 12 TrialNet Clinical Centers between
126 patients were assessed; 39 were excluded; 87 underwent randomization (57 were assigned to receive rituximab and 30 were assigned to receive placebo)
Participant milestones
| Measure |
Rituximab Treatment
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
|---|---|---|
|
Overall Study
STARTED
|
57
|
30
|
|
Overall Study
COMPLETED
|
49
|
29
|
|
Overall Study
NOT COMPLETED
|
8
|
1
|
Reasons for withdrawal
| Measure |
Rituximab Treatment
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
|---|---|---|
|
Overall Study
Pregnancy
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Dificulting establishing IV
|
1
|
0
|
|
Overall Study
FDA Safety Alert
|
4
|
1
|
Baseline Characteristics
Rituximab in New Onset Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Rituximab Treatment
n=57 Participants
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
n=30 Participants
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
19.0 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
17.4 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
18.5 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: When all participants complete the 1 year visitThe 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. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.
Outcome measures
| Measure |
Rituximab Treatment
n=49 Participants
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
n=29 Participants
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
|---|---|---|
|
Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4-hour Mixed Meal Tolerance Test (MMTT) Administered at 1 Year
|
0.58 pmol per mL
Interval 0.476 to 0.691
|
0.429 pmol per mL
Interval 0.289 to 0.585
|
Adverse Events
Rituximab Treatment
Serious events: 11 serious events
Other events: 56 other events
Deaths: 0 deaths
Placebo
Serious events: 9 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab Treatment
n=57 participants at risk
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
n=30 participants at risk
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
|---|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
7.0%
4/57 • Number of events 4
|
3.3%
1/30 • Number of events 2
|
|
General disorders
Sudden Death
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin Other
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Endocrine disorders
Endocrine- other
|
3.5%
2/57 • Number of events 2
|
6.7%
2/30 • Number of events 3
|
|
Endocrine disorders
Pancreatic endocrine: glucose intolerance
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal Other
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Infections and infestations
Infection Other
|
0.00%
0/57
|
6.7%
2/30 • Number of events 2
|
|
Infections and infestations
Infection with unknown ANC- pneumonia
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Infections and infestations
Infection with unknown ANC- Sinus
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)
|
1.8%
1/57 • Number of events 1
|
3.3%
1/30 • Number of events 3
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
1.8%
1/57 • Number of events 1
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
|
Surgical and medical procedures
Intra-operative Injury - Other
|
0.00%
0/57
|
3.3%
1/30 • Number of events 1
|
Other adverse events
| Measure |
Rituximab Treatment
n=57 participants at risk
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
|
Placebo
n=30 participants at risk
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
|
|---|---|---|
|
Immune system disorders
Allergic rhinitis
|
17.5%
10/57 • Number of events 11
|
10.0%
3/30 • Number of events 5
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow - Other
|
0.00%
0/57
|
10.0%
3/30 • Number of events 9
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
12.3%
7/57 • Number of events 12
|
6.7%
2/30 • Number of events 3
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.8%
5/57 • Number of events 7
|
6.7%
2/30 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
19.3%
11/57 • Number of events 18
|
30.0%
9/30 • Number of events 14
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia
|
21.1%
12/57 • Number of events 13
|
0.00%
0/30
|
|
Cardiac disorders
Vasovagal episode
|
5.3%
3/57 • Number of events 5
|
6.7%
2/30 • Number of events 2
|
|
Cardiac disorders
Hypertension
|
10.5%
6/57 • Number of events 6
|
0.00%
0/30
|
|
Cardiac disorders
Hypotension
|
31.6%
18/57 • Number of events 25
|
16.7%
5/30 • Number of events 9
|
|
General disorders
Constitutional Symptoms - Other
|
5.3%
3/57 • Number of events 3
|
6.7%
2/30 • Number of events 3
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
10.5%
6/57 • Number of events 8
|
6.7%
2/30 • Number of events 2
|
|
General disorders
Fever
|
29.8%
17/57 • Number of events 19
|
16.7%
5/30 • Number of events 7
|
|
General disorders
Rigors/chills
|
5.3%
3/57 • Number of events 3
|
0.00%
0/30
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
10.5%
6/57 • Number of events 9
|
20.0%
6/30 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
36.8%
21/57 • Number of events 22
|
0.00%
0/30
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
42.1%
24/57 • Number of events 26
|
10.0%
3/30 • Number of events 4
|
|
Endocrine disorders
Endocrine - Other
|
0.00%
0/57
|
16.7%
5/30 • Number of events 5
|
|
Gastrointestinal disorders
Dental: teeth
|
8.8%
5/57 • Number of events 5
|
0.00%
0/30
|
|
Gastrointestinal disorders
Diarrhea
|
21.1%
12/57 • Number of events 15
|
10.0%
3/30 • Number of events 5
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
7.0%
4/57 • Number of events 4
|
16.7%
5/30 • Number of events 6
|
|
Gastrointestinal disorders
Nausea
|
43.9%
25/57 • Number of events 26
|
6.7%
2/30 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
28.1%
16/57 • Number of events 19
|
10.0%
3/30 • Number of events 3
|
|
Infections and infestations
Infection - Other
|
24.6%
14/57 • Number of events 15
|
6.7%
2/30 • Number of events 2
|
|
Infections and infestations
Pelvis Infection with normal ANC or Grade 1 or 2 neutrophils
|
5.3%
3/57 • Number of events 3
|
6.7%
2/30 • Number of events 2
|
|
Infections and infestations
Skin Infection with normal ANC or Grade 1 or 2 neutrophils
|
7.0%
4/57 • Number of events 4
|
6.7%
2/30 • Number of events 2
|
|
Infections and infestations
Pharynx Infection with unknown ANC
|
14.0%
8/57 • Number of events 14
|
13.3%
4/30 • Number of events 8
|
|
Infections and infestations
Sinus Infection with unknown ANC
|
5.3%
3/57 • Number of events 3
|
6.7%
2/30 • Number of events 6
|
|
Infections and infestations
Upper Airway Infection with unknown ANC
|
24.6%
14/57 • Number of events 25
|
40.0%
12/30 • Number of events 22
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
8.8%
5/57 • Number of events 5
|
13.3%
4/30 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
12.3%
7/57 • Number of events 9
|
13.3%
4/30 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other
|
21.1%
12/57 • Number of events 15
|
23.3%
7/30 • Number of events 11
|
|
Nervous system disorders
Dizziness
|
5.3%
3/57 • Number of events 3
|
0.00%
0/30
|
|
Nervous system disorders
Neurology - Other
|
5.3%
3/57 • Number of events 4
|
0.00%
0/30
|
|
General disorders
Sinus Pain
|
22.8%
13/57 • Number of events 22
|
23.3%
7/30 • Number of events 13
|
|
General disorders
Other AE
|
8.8%
5/57 • Number of events 7
|
13.3%
4/30 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing
|
0.00%
0/57
|
6.7%
2/30 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.0%
8/57 • Number of events 10
|
13.3%
4/30 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
7.0%
4/57 • Number of events 5
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Edema, larynx
|
10.5%
6/57 • Number of events 7
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other
|
5.3%
3/57 • Number of events 4
|
6.7%
2/30 • Number of events 2
|
|
Reproductive system and breast disorders
Sexual/Reproductive Function - Other
|
5.3%
3/57 • Number of events 4
|
0.00%
0/30
|
|
General disorders
Flu-like syndrome
|
7.0%
4/57 • Number of events 5
|
6.7%
2/30 • Number of events 2
|
|
Vascular disorders
Vascular - Other
|
5.3%
3/57 • Number of events 5
|
0.00%
0/30
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place