Type 1 Diabetes Mellitus
Conditions
Keywords
Teplizumab, Protege, MGA031, Monoclonal antibody, Type 1 Diabetes Mellitus, T1DM, MacroGenics
Brief summary
The purpose of this study is to assess the long term safety and efficacy in subjects with Type 1 Diabetes Mellitus who completed the Protege Study (CP-MGA031-01).
Detailed description
The primary objective of the extension study is to assess long-term safety, with particular focus on the development of serious adverse events (SAEs), adverse events of special interest (AESIs) including opportunistic infections and lymphoproliferative disease, and other immediately reportable events (IREs), in subjects with recent-onset T1DM who complete CP-MGA031-01. The secondary objectives of the extension study are to: 1) assess long-term efficacy; 2) evaluate immunological effects(North America only); 3) measure anti-teplizumab antibody levels;4) assess Health Related Quality of Life Questionnaires.
Interventions
DIAGNOSTIC_TESTBlood samples for safety
serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
BEHAVIORALPatient reported outcome questionnaires
EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
DIAGNOSTIC_TESTAnalysis of T-cell subsets
CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets
Sponsors
Eli Lilly and Company
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 37 Years
Healthy volunteers
No
Inclusion criteria
1. Complete Protocol CP-MGA031-01 (i.e., all subjects who complete Study Day 728, regardless of how many doses of study drug are received). 2. Provide written informed consent.
Exclusion criteria
None
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | Duration of study participation up to 15 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With HbA1c <6.5% | Month 6 | — |
| Mean HbA1c at 6 Months | 6 months | — |
| Mean HbA1c at 12 Months | Month 12 | — |
| C-peptide Area Under the Curve (AUC) at 6 Months | Month 6 | This outcome measure summarizes the mean and standard deviation of the observed value. |
| C-peptide AUC at 12 Months | Month 12 | This outcome measure summarizes the mean and standard deviation of the observed value. |
| Total Daily Insulin Usage at 6 Months | Month 6 | — |
| Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | Month 6 | — |
| Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | Month 6 | The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life. |
| Mean Values for Participant-reported Outcomes on the EQ-5D | Month 12 | The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life. |
| Pediatric Quality of Life Questionnaire Total Score | Month 6 | The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed. |
| Percentage of Cells by Immunophenotype | Month 6 | — |
| Human Anti-human Antibody (HAHA) Levels | Month 6 and 12 | Patients with HAHA levels \> 0. |
| Total Daily Insulin Usage at 12 Months | Month 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Herold Regimen Patients who had been assigned to Herold Regimen in Segment 1 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.
Blood samples for safety: serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
Patient reported outcome questionnaires: EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
Analysis of T-cell subsets: CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets | 32 |
| Double-blind Herold Regimen Patients who had been assigned to Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.
Blood samples for safety: serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
Patient reported outcome questionnaires: EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
Analysis of T-cell subsets: CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets | 73 |
| Double-blind 33.3% Herold Regimen Patients who had been assigned to 33.3% Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.
Blood samples for safety: serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
Patient reported outcome questionnaires: EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
Analysis of T-cell subsets: CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets | 38 |
| Double-blind Curtailed Herold Regimen Patients who had been assigned to Curtailed Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.
Blood samples for safety: serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
Patient reported outcome questionnaires: EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
Analysis of T-cell subsets: CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets | 38 |
| Double-blind Placebo Patients who had been assigned to Placebo in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.
Blood samples for safety: serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies
Patient reported outcome questionnaires: EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.
Analysis of T-cell subsets: CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets | 38 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Terminated by sponsor | 29 | 70 | 36 | 36 | 38 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Open-label Herold Regimen | Total | Double-blind Placebo | Double-blind Curtailed Herold Regimen | Double-blind 33.3% Herold Regimen | Double-blind Herold Regimen |
|---|---|---|---|---|---|---|
| Age, Continuous | 14.0 years | 18.0 years | 16.5 years | 16.0 years | 18.5 years | 18.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 214 Participants | 38 Participants | 37 Participants | 37 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 72 Participants | 15 Participants | 13 Participants | 12 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 146 Participants | 23 Participants | 25 Participants | 26 Participants | 45 Participants |
| Region of Enrollment Czechia | 7 participants | 27 participants | 4 participants | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Estonia | 1 participants | 4 participants | 1 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment India | 5 participants | 71 participants | 15 participants | 13 participants | 12 participants | 26 participants |
| Region of Enrollment Israel | 0 participants | 14 participants | 4 participants | 2 participants | 4 participants | 4 participants |
| Region of Enrollment Latvia | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Poland | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Romania | 4 participants | 12 participants | 2 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Spain | 0 participants | 9 participants | 2 participants | 1 participants | 2 participants | 4 participants |
| Region of Enrollment Sweden | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Ukraine | 0 participants | 15 participants | 2 participants | 3 participants | 4 participants | 6 participants |
| Region of Enrollment United States | 16 participants | 65 participants | 8 participants | 11 participants | 11 participants | 19 participants |
| Sex: Female, Male Female | 7 Participants | 74 Participants | 14 Participants | 9 Participants | 12 Participants | 32 Participants |
| Sex: Female, Male Male | 25 Participants | 145 Participants | 24 Participants | 29 Participants | 26 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 1 / 73 | 0 / 38 | 0 / 38 | 0 / 38 |
| other Total, other adverse events | 8 / 32 | 2 / 73 | 1 / 38 | 10 / 38 | 4 / 38 |
| serious Total, serious adverse events | 1 / 32 | 5 / 73 | 3 / 38 | 4 / 38 | 0 / 38 |
Outcome results
Primary
The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest.
Time frame: Duration of study participation up to 15 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Herold Regimen | The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | 8 Participants |
| Double-blind Herold Regimen | The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | 8 Participants |
| Double-blind 33.3% Herold Regimen | The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | 3 Participants |
| Double-blind Curtailed Herold Regimen | The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | 10 Participants |
| Double-blind Placebo | The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. | 4 Participants |
Secondary
C-peptide Area Under the Curve (AUC) at 6 Months
This outcome measure summarizes the mean and standard deviation of the observed value.
Time frame: Month 6
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | C-peptide Area Under the Curve (AUC) at 6 Months | 0.30 min*nmol/L | Standard Deviation 0.195 |
| Double-blind Herold Regimen | C-peptide Area Under the Curve (AUC) at 6 Months | 0.45 min*nmol/L | Standard Deviation 0.36 |
| Double-blind 33.3% Herold Regimen | C-peptide Area Under the Curve (AUC) at 6 Months | 0.25 min*nmol/L | Standard Deviation 0.301 |
| Double-blind Curtailed Herold Regimen | C-peptide Area Under the Curve (AUC) at 6 Months | 0.25 min*nmol/L | Standard Deviation 0.248 |
| Double-blind Placebo | C-peptide Area Under the Curve (AUC) at 6 Months | 0.37 min*nmol/L | Standard Deviation 0.399 |
Secondary
C-peptide AUC at 12 Months
This outcome measure summarizes the mean and standard deviation of the observed value.
Time frame: Month 12
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | C-peptide AUC at 12 Months | 0.32 min*nmol/L | Standard Deviation 0.183 |
| Double-blind Herold Regimen | C-peptide AUC at 12 Months | 0.56 min*nmol/L | Standard Deviation 0.123 |
| Double-blind 33.3% Herold Regimen | C-peptide AUC at 12 Months | 0.26 min*nmol/L | Standard Deviation 0.276 |
| Double-blind Curtailed Herold Regimen | C-peptide AUC at 12 Months | 0.59 min*nmol/L | Standard Deviation 0.036 |
| Double-blind Placebo | C-peptide AUC at 12 Months | 0.19 min*nmol/L | Standard Deviation 0.058 |
Secondary
Human Anti-human Antibody (HAHA) Levels
Patients with HAHA levels \> 0.
Time frame: Month 6 and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 6 | 30 Participants |
| Open-label Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 12 | 26 Participants |
| Double-blind Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 12 | 2 Participants |
| Double-blind Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 6 | 22 Participants |
| Double-blind 33.3% Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 12 | 2 Participants |
| Double-blind 33.3% Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 6 | 13 Participants |
| Double-blind Curtailed Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 12 | 2 Participants |
| Double-blind Curtailed Herold Regimen | Human Anti-human Antibody (HAHA) Levels | Month 6 | 12 Participants |
| Double-blind Placebo | Human Anti-human Antibody (HAHA) Levels | Month 12 | 2 Participants |
| Double-blind Placebo | Human Anti-human Antibody (HAHA) Levels | Month 6 | 11 Participants |
Secondary
Mean HbA1c at 12 Months
Time frame: Month 12
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Mean HbA1c at 12 Months | 7.81 percentage of glycosylated hemoglobin | Standard Deviation 2.155 |
| Double-blind Herold Regimen | Mean HbA1c at 12 Months | 6.30 percentage of glycosylated hemoglobin | Standard Deviation 0.141 |
| Double-blind 33.3% Herold Regimen | Mean HbA1c at 12 Months | 6.35 percentage of glycosylated hemoglobin | Standard Deviation 0.354 |
| Double-blind Curtailed Herold Regimen | Mean HbA1c at 12 Months | 6.05 percentage of glycosylated hemoglobin | Standard Deviation 0.778 |
| Double-blind Placebo | Mean HbA1c at 12 Months | 6.95 percentage of glycosylated hemoglobin | Standard Deviation 0.919 |
Secondary
Mean HbA1c at 6 Months
Time frame: 6 months
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Mean HbA1c at 6 Months | 8.24 percentage of glycosylated hemoglobin | Standard Deviation 2.063 |
| Double-blind Herold Regimen | Mean HbA1c at 6 Months | 8.25 percentage of glycosylated hemoglobin | Standard Deviation 0.262 |
| Double-blind 33.3% Herold Regimen | Mean HbA1c at 6 Months | 8.25 percentage of glycosylated hemoglobin | Standard Deviation 2.709 |
| Double-blind Curtailed Herold Regimen | Mean HbA1c at 6 Months | 7.83 percentage of glycosylated hemoglobin | Standard Deviation 1.489 |
| Double-blind Placebo | Mean HbA1c at 6 Months | 8.10 percentage of glycosylated hemoglobin | Standard Deviation 1.009 |
Secondary
Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D)
The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life.
Time frame: Month 6
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | 5.3 units on a scale | Standard Deviation 0.53 |
| Double-blind Herold Regimen | Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | 5.8 units on a scale | Standard Deviation 1.25 |
| Double-blind 33.3% Herold Regimen | Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | 5.2 units on a scale | Standard Deviation 0.63 |
| Double-blind Curtailed Herold Regimen | Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | 5.1 units on a scale | Standard Deviation 0.3 |
| Double-blind Placebo | Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | 5.7 units on a scale | Standard Deviation 1.12 |
Secondary
Mean Values for Participant-reported Outcomes on the EQ-5D
The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life.
Time frame: Month 12
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Mean Values for Participant-reported Outcomes on the EQ-5D | 5.1 units on a scale | Standard Deviation 0.33 |
| Double-blind Herold Regimen | Mean Values for Participant-reported Outcomes on the EQ-5D | 6.52 units on a scale | Standard Deviation 2.12 |
| Double-blind 33.3% Herold Regimen | Mean Values for Participant-reported Outcomes on the EQ-5D | 5.0 units on a scale | Standard Deviation 0 |
| Double-blind Curtailed Herold Regimen | Mean Values for Participant-reported Outcomes on the EQ-5D | 5.0 units on a scale | Standard Deviation 0 |
| Double-blind Placebo | Mean Values for Participant-reported Outcomes on the EQ-5D | 6.0 units on a scale | Standard Deviation 1.41 |
Secondary
Pediatric Quality of Life Questionnaire Total Score
The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed.
Time frame: Month 12
Population: Pediatric patients completing PedQL questionnaire. Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 6.3 units on a scale | Standard Deviation 6.39 |
| Double-blind Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 21.0 units on a scale | Standard Deviation 26.87 |
| Double-blind 33.3% Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 6.5 units on a scale | Standard Deviation 2.12 |
| Double-blind Curtailed Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 11.0 units on a scale | Standard Deviation 9.9 |
| Double-blind Placebo | Pediatric Quality of Life Questionnaire Total Score | 30.5 units on a scale | Standard Deviation 7.78 |
Secondary
Pediatric Quality of Life Questionnaire Total Score
The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed.
Time frame: Month 6
Population: Pediatric patients who completed the questionnaire. Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 7.7 units on a scale | Standard Deviation 6.82 |
| Double-blind Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 13.5 units on a scale | Standard Deviation 13.07 |
| Double-blind 33.3% Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 12.2 units on a scale | Standard Deviation 8.82 |
| Double-blind Curtailed Herold Regimen | Pediatric Quality of Life Questionnaire Total Score | 9.3 units on a scale | Standard Deviation 10.52 |
| Double-blind Placebo | Pediatric Quality of Life Questionnaire Total Score | 13.8 units on a scale | Standard Deviation 15.66 |
Secondary
Percentage of Cells by Immunophenotype
Time frame: Month 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD4+] | 0.4 Percent | Standard Deviation 1.87 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD8+] | 3.7 Percent | Standard Deviation 1.71 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD4+] | 0.9 Percent | Standard Deviation 0.77 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD3+/CD16,CD56+ | 6.7 Percent | Standard Deviation 4.39 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD8+] | 0.2 Percent | Standard Deviation 0.33 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD3-/CD16,CD56+ | 8.9 Percent | Standard Deviation 3.32 |
| Open-label Herold Regimen | Percentage of Cells by Immunophenotype | %CD40+ [of CD4+] | 0.7 Percent | Standard Deviation 0.49 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD40+ [of CD4+] | 1.1 Percent | Standard Deviation 0.48 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD3-/CD16,CD56+ | 9.1 Percent | Standard Deviation 3.23 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD8+] | 0.5 Percent | Standard Deviation 0.3 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD4+] | 5.5 Percent | Standard Deviation 1.35 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD4+] | 0.1 Percent | Standard Deviation 0.09 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD3+/CD16,CD56+ | 4.4 Percent | Standard Deviation 1.52 |
| Double-blind Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD8+] | 3.3 Percent | Standard Deviation 0.23 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD3-/CD16,CD56+ | 6.4 Percent | Standard Deviation 3.09 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD4+] | 4.8 Percent | Standard Deviation 1 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD8+] | 0.4 Percent | Standard Deviation 0.1 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD3+/CD16,CD56+ | 7.7 Percent | Standard Deviation 2.85 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD40+ [of CD4+] | 0.9 Percent | Standard Deviation 0.89 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD4+] | 0.7 Percent | Standard Deviation 1.2 |
| Double-blind 33.3% Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD8+] | 3.4 Percent | Standard Deviation 1.39 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD3+/CD16,CD56+ | 4.8 Percent | Standard Deviation 1.63 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD40+ [of CD4+] | 0.8 Percent | Standard Deviation 0.54 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD8+] | 0.7 Percent | Standard Deviation 0.46 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD8+] | 3.4 Percent | Standard Deviation 1.25 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD69+ [of CD4+] | 0.1 Percent | Standard Deviation 0.12 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD4+] | 6.0 Percent | Standard Deviation 1.28 |
| Double-blind Curtailed Herold Regimen | Percentage of Cells by Immunophenotype | %CD3-/CD16,CD56+ | 10.7 Percent | Standard Deviation 4.31 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD3+/CD16,CD56+ | 4.2 Percent | Standard Deviation 1.02 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD69+ [of CD8+] | 4.2 Percent | Standard Deviation 1.16 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD69+ [of CD4+] | 0.1 Percent | Standard Deviation 0.1 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD40+ [of CD4+] | 0.8 Percent | Standard Deviation 0.52 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD8+] | 0.6 Percent | Standard Deviation 0.35 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD25+/FOXp3+ [of CD4+] | 4.5 Percent | Standard Deviation 1.46 |
| Double-blind Placebo | Percentage of Cells by Immunophenotype | %CD3-/CD16,CD56+ | 5.8 Percent | Standard Deviation 2.11 |
Secondary
Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.
Time frame: Month 6
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 3 Participants |
| Double-blind Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 3 Participants |
| Double-blind 33.3% Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 0 Participants |
| Double-blind Curtailed Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 1 Participants |
| Double-blind Placebo | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 0 Participants |
Secondary
Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.
Time frame: Month 12
Population: Because the study was terminated early with a limited number of subjects and subject visits, the data are only summarized. Too few data are available for meaningful analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 4 Participants |
| Double-blind Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 1 Participants |
| Double-blind 33.3% Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 0 Participants |
| Double-blind Curtailed Herold Regimen | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 1 Participants |
| Double-blind Placebo | Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. | 0 Participants |
Secondary
Proportion of Subjects With HbA1c <6.5%
Time frame: Month 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Herold Regimen | Proportion of Subjects With HbA1c <6.5% | 5 Participants |
| Double-blind Herold Regimen | Proportion of Subjects With HbA1c <6.5% | 6 Participants |
| Double-blind 33.3% Herold Regimen | Proportion of Subjects With HbA1c <6.5% | 3 Participants |
| Double-blind Curtailed Herold Regimen | Proportion of Subjects With HbA1c <6.5% | 2 Participants |
| Double-blind Placebo | Proportion of Subjects With HbA1c <6.5% | 0 Participants |
Secondary
Total Daily Insulin Usage at 12 Months
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Total Daily Insulin Usage at 12 Months | 0.67 units/kg/day | Standard Deviation 0.28 |
| Double-blind Herold Regimen | Total Daily Insulin Usage at 12 Months | 0.47 units/kg/day | Standard Deviation 0.073 |
| Double-blind 33.3% Herold Regimen | Total Daily Insulin Usage at 12 Months | 0.49 units/kg/day | Standard Deviation 0.076 |
| Double-blind Curtailed Herold Regimen | Total Daily Insulin Usage at 12 Months | 0.40 units/kg/day | Standard Deviation 0.147 |
| Double-blind Placebo | Total Daily Insulin Usage at 12 Months | 0.76 units/kg/day | Standard Deviation 0.272 |
Secondary
Total Daily Insulin Usage at 6 Months
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Herold Regimen | Total Daily Insulin Usage at 6 Months | 0.71 units/kg/day | Standard Deviation 0.362 |
| Double-blind Herold Regimen | Total Daily Insulin Usage at 6 Months | 0.71 units/kg/day | Standard Deviation 0.451 |
| Double-blind 33.3% Herold Regimen | Total Daily Insulin Usage at 6 Months | 0.64 units/kg/day | Standard Deviation 0.274 |
| Double-blind Curtailed Herold Regimen | Total Daily Insulin Usage at 6 Months | 0.81 units/kg/day | Standard Deviation 0.433 |
| Double-blind Placebo | Total Daily Insulin Usage at 6 Months | 0.60 units/kg/day | Standard Deviation 0.251 |