Trial Outcomes & Findings for Reversing Type 1 Diabetes After it is Established (NCT NCT01106157)
NCT ID: NCT01106157
Last Updated: 2019-08-05
Results Overview
Area Under Curve (AUC) C-peptide production. Subjects underwent a 2 hour mixed meal tolerance test (MMTT) using a 6ml/kg load of boost to stimulate insulin production. Samples were collected at baseline, 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes. AUC was then calculated. Subjects repeated the MMTT at baseline, 3, 6, 9, and 12 months following ATG/GCSF or placebo. The primary outcome for the study was the change over 12 months in AUC C-peptide (1 year - baseline) for those who received ATG/GCSF versus the change in AUC C-peptide (1 year - baseline) for those who received placebo
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Baseline and 12 months
Results posted on
2019-08-05
Participant Flow
Participant milestones
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose) given subcutaneously every 2 weeks beginning after the ATG infusion.
|
Placebo
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner.
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes.
|
|---|---|---|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
|
Overall Study
STARTED
|
17
|
8
|
|
Overall Study
COMPLETED
|
16
|
8
|
Reasons for withdrawal
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose) given subcutaneously every 2 weeks beginning after the ATG infusion.
|
Placebo
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner.
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Reversing Type 1 Diabetes After it is Established
Baseline characteristics by cohort
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=17 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
23.64 years
STANDARD_DEVIATION 10 • n=5 Participants
|
23.55 years
STANDARD_DEVIATION 10.6 • n=7 Participants
|
23.61 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
8 participants
n=7 Participants
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 monthsArea Under Curve (AUC) C-peptide production. Subjects underwent a 2 hour mixed meal tolerance test (MMTT) using a 6ml/kg load of boost to stimulate insulin production. Samples were collected at baseline, 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes. AUC was then calculated. Subjects repeated the MMTT at baseline, 3, 6, 9, and 12 months following ATG/GCSF or placebo. The primary outcome for the study was the change over 12 months in AUC C-peptide (1 year - baseline) for those who received ATG/GCSF versus the change in AUC C-peptide (1 year - baseline) for those who received placebo
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Metabolic Function Baseline to 12 Months.
|
0.74 nmol/L/min
Standard Deviation 0.47
|
0.43 nmol/L/min
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Change in Baseline to 12 monthsChange in regulatory T cells (Treg) baseline to 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months
|
-0.46 percentage change
Standard Deviation 0.36
|
0 percentage change
Standard Deviation .036
|
SECONDARY outcome
Timeframe: Change in baseline to 12 monthsChange in A1c baseline to 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
A1c
|
0.47 % change
Standard Deviation 1.88
|
0.98 % change
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsPopulation: Insulin use data was not provided by all subjects resulting in sampling for analysis that was smaller than the cohort for the entire study.
Change in Insulin Requirements, baseline to 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=14 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=5 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Insulin Requirements, Baseline to 12 Months
|
-0.03 units/kg/day
Standard Deviation 0.4
|
0.08 units/kg/day
Standard Deviation 0.19
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in Glutamic Acid Decarboxylase Antibodies (GADA) over 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months
|
-17.75 nmol/L
Standard Deviation 225.81
|
-29.5 nmol/L
Standard Deviation 38.96
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in Insulin Autoantibodies (IAA) over 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months
|
0.12 Units/mL
Standard Deviation 0.5
|
-0.15 Units/mL
Standard Deviation 0.43
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in Insulinoma Associated 2 Autoantibodies (IA-2A)
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Insulinoma Associated 2 Autoantibodies (IA-2A) From Baseline to 12 Months
|
-21.63 nmol/L
Standard Deviation 50.3
|
2.5 nmol/L
Standard Deviation 31.47
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in Zinc Transporter 8 Autoantibodies (ZnT8A) over 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in Zinc Transporter 8 Autoantibodies (ZnT8A) From Baseline to 12 Months
|
-0.07 nmol/L
Standard Deviation 0.17
|
-0.10 nmol/L
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in Neutrophil Count over 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Percentage of Neutrophils
|
0.21 Percentage of neutrophils
Standard Deviation 0.69
|
0.44 Percentage of neutrophils
Standard Deviation 1.19
|
SECONDARY outcome
Timeframe: Change from baseline to 12 monthsChange in WBC over 12 months
Outcome measures
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 Participants
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 Participants
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Change in White Blood Count (WBC) From Baseline to 12 Months
|
-0.51 Change in percentage of WBC
Standard Deviation 0.81
|
0.4 Change in percentage of WBC
Standard Deviation 1.25
|
Adverse Events
Anti-Thymocyte Globin Plus Pegylated GCSF
Serious events: 15 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 participants at risk
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 participants at risk
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Immune system disorders
Lymphocyte Count Decreased
|
93.8%
15/16 • Number of events 15 • 12 months
|
37.5%
3/8 • Number of events 5 • 12 months
|
|
Immune system disorders
Serum Sickness
|
81.2%
13/16 • Number of events 13 • 12 months
|
0.00%
0/8 • 12 months
|
|
Immune system disorders
Cytokine Release Syndrome
|
87.5%
14/16 • Number of events 14 • 12 months
|
0.00%
0/8 • 12 months
|
Other adverse events
| Measure |
Anti-Thymocyte Globin Plus Pegylated GCSF
n=16 participants at risk
Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks.
Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
|
Placebo
n=8 participants at risk
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes
|
|---|---|---|
|
Endocrine disorders
Elevated Alk Phos
|
43.8%
7/16 • Number of events 7 • 12 months
|
0.00%
0/8 • 12 months
|
|
Blood and lymphatic system disorders
Anemia
|
37.5%
6/16 • Number of events 6 • 12 months
|
37.5%
3/8 • Number of events 3 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
56.2%
9/16 • Number of events 9 • 12 months
|
0.00%
0/8 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
56.2%
9/16 • Number of events 9 • 12 months
|
0.00%
0/8 • 12 months
|
|
Immune system disorders
Chills
|
37.5%
6/16 • Number of events 6 • 12 months
|
12.5%
1/8 • Number of events 1 • 12 months
|
|
General disorders
Fatigue
|
37.5%
6/16 • Number of events 6 • 12 months
|
37.5%
3/8 • Number of events 3 • 12 months
|
|
General disorders
Headache
|
81.2%
13/16 • Number of events 13 • 12 months
|
50.0%
4/8 • Number of events 4 • 12 months
|
|
Endocrine disorders
Hypoglycemia
|
75.0%
12/16 • Number of events 12 • 12 months
|
62.5%
5/8 • Number of events 5 • 12 months
|
|
Endocrine disorders
Hyponatremia
|
18.8%
3/16 • Number of events 5 • 12 months
|
25.0%
2/8 • Number of events 4 • 12 months
|
|
General disorders
Nausea
|
31.2%
5/16 • Number of events 8 • 12 months
|
0.00%
0/8 • 12 months
|
|
General disorders
Others
|
93.8%
15/16 • Number of events 84 • 12 months
|
62.5%
5/8 • Number of events 41 • 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place