Trial Outcomes & Findings for Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus (NCT NCT00505375)
NCT ID: NCT00505375
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
2 years of follow up
Results posted on
2020-05-06
Participant Flow
Participant milestones
| Measure |
CTLA-4 Ig
Intravenous infusions of CTLA-4 Ig
CTLA-4 Ig: Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
Intravenous infusions of placebo
Placebo: Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
|---|---|---|
|
Overall Study
STARTED
|
77
|
35
|
|
Overall Study
COMPLETED
|
73
|
30
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
CTLA-4 Ig
Intravenous infusions of CTLA-4 Ig
CTLA-4 Ig: Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
Intravenous infusions of placebo
Placebo: Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
|
Overall Study
Pregnancy
|
1
|
0
|
|
Overall Study
Travel issues
|
0
|
1
|
Baseline Characteristics
Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
CTLA-4 Ig
n=77 Participants
Intravenous infusions of CTLA-4 Ig
CTLA-4 Ig: Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
n=35 Participants
Intravenous infusions of placebo
Placebo: Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.9 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
13.7 years
STANDARD_DEVIATION 5.3 • n=7 Participants
|
13.9 years
STANDARD_DEVIATION 6.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 years of follow upThe 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 |
CTLA-4 Ig
n=73 Participants
Intravenous infusions 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
n=30 Participants
Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
|---|---|---|
|
Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 2 Year Visit
|
0.375 nmol/L
Interval 0.29 to 0.465
|
0.266 nmol/L
Interval 0.171 to 0.368
|
Adverse Events
CTLA-4 Ig
Serious events: 11 serious events
Other events: 60 other events
Deaths: 0 deaths
Placebo
Serious events: 7 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CTLA-4 Ig
n=77 participants at risk
Intravenous infusions of CTLA-4 Ig
CTLA-4 Ig: Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
n=35 participants at risk
Intravenous infusions of placebo
Placebo: Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Insomnia
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
General disorders
Death not associated with CTCAE term
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
1.3%
1/77 • Number of events 1
|
2.9%
1/35 • Number of events 1
|
|
Endocrine disorders
Endocrine - Other
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
Endocrine disorders
Pancreatic endocrine: glucose intolerance
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
3.9%
3/77 • Number of events 3
|
8.6%
3/35 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
3.9%
3/77 • Number of events 5
|
2.9%
1/35 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
2.6%
2/77 • Number of events 2
|
0.00%
0/35
|
|
Nervous system disorders
Mood alteration- Agitation
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
Nervous system disorders
Seizure
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
General disorders
Pain- Head/headache
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Secondary Malignancy - possibly related to cancer treatment
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
Surgical and medical procedures
Intra-operative Injury - Other
|
1.3%
1/77 • Number of events 1
|
0.00%
0/35
|
|
General disorders
Syndromes - Other
|
0.00%
0/77
|
2.9%
1/35 • Number of events 1
|
Other adverse events
| Measure |
CTLA-4 Ig
n=77 participants at risk
Intravenous infusions of CTLA-4 Ig
CTLA-4 Ig: Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
|
Placebo
n=35 participants at risk
Intravenous infusions of placebo
Placebo: Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
11.7%
9/77 • Number of events 14
|
14.3%
5/35 • Number of events 12
|
|
General disorders
Constitutional Symptoms - Other
|
6.5%
5/77 • Number of events 6
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
10.4%
8/77 • Number of events 9
|
2.9%
1/35 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
15.6%
12/77 • Number of events 14
|
2.9%
1/35 • Number of events 2
|
|
Endocrine disorders
Endocrine - Other
|
6.5%
5/77 • Number of events 5
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Dental: teeth
|
6.5%
5/77 • Number of events 5
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
6.5%
5/77 • Number of events 5
|
5.7%
2/35 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
15.6%
12/77 • Number of events 16
|
11.4%
4/35 • Number of events 4
|
|
Infections and infestations
Infection - Other
|
36.4%
28/77 • Number of events 58
|
37.1%
13/35 • Number of events 23
|
|
Infections and infestations
Infection with unknown ANC- Pharynx
|
1.3%
1/77 • Number of events 1
|
8.6%
3/35 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
11.7%
9/77 • Number of events 12
|
14.3%
5/35 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other
|
7.8%
6/77 • Number of events 7
|
8.6%
3/35 • Number of events 3
|
|
Nervous system disorders
Neuropathy: sensory
|
0.00%
0/77
|
5.7%
2/35 • Number of events 2
|
|
General disorders
Other AE
|
5.2%
4/77 • Number of events 4
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Pain- Head/headache
|
1.3%
1/77 • Number of events 1
|
5.7%
2/35 • Number of events 2
|
|
General disorders
Pain - Other
|
2.6%
2/77 • Number of events 3
|
8.6%
3/35 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing
|
1.3%
1/77 • Number of events 1
|
5.7%
2/35 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.3%
1/77 • Number of events 1
|
5.7%
2/35 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other
|
10.4%
8/77 • Number of events 14
|
5.7%
2/35 • Number of events 2
|
|
General disorders
Flu-like syndrome
|
9.1%
7/77 • Number of events 7
|
11.4%
4/35 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place