Type 1 Diabetes Mellitus
Conditions
Brief summary
This is a double-blind, randomized , placebo-controlled study to evaluate the safety and tolerability of AVT001, and to assess AVT001 as a potential treatment for type 1 diabetes (T1D). The trial will involve approximately 24 new-onset T1D subjects.
Interventions
DRUGAVT001
autologous dendritic cell therapy
OTHERPlacebo
matched placebo
Sponsors
Avotres Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of type 1 diabetes, within 12 months of first dosing, confirmed by positive lab result for one or more of the following types of autoantibodies: 1. Glutamic acid decarboxylase (GAD65) 2. Insulinoma associated protein 2 (IA-2, also known as ICA-512) 3. Zinc transporter 8 (ZnT8). 2. Age 16 or older and able to provide informed consent/assent. 3. If a participant is female with reproductive potential, willing to avoid pregnancy through the duration of the trial. 4. Signed and dated written informed consent/assent. Key
Exclusion criteria
1. Poorly controlled diabetes despite insulin therapy, who in the opinion of the investigator would not be a good candidate for participation in a clinical trial 2. Screening hemoglobin \<10.0 g/dL; leukocytes \<3,000/uL; neutrophils \<1,500/uL; lymphocytes \<800/uL; platelets \<100,000/uL 3. Screening Urine Albumin Excretion \> 300mg/gmCr 4. Screening eGFR \< 60 mL/min/1.73m2 5. Screening ALT or AST \> 1.5x upper limit of normal (ULN) 6. Screening bilirubin \> 2.0 mg / dL, or \> 3.0 mg / dL for participants with Gilbert's Syndrome 7. Current use of immunosuppressive or immunomodulatory therapies, including pharmacologic doses of systemic steroids. However, topical steroidal creams and inhaled steroids without large systemic absorption are allowed. 8. Coincident medical condition likely to require immunosuppressive or immunomodulatory therapies. 9. Coincident medical condition likely to limit short term (5 year) life expectancy (malignancy, symptomatic coronary artery disease, recent stroke) 10. Prior radiation therapy, immunotherapy (within 1 year of screening), or chemotherapy 11. Serologic evidence of current HIV-1 or HIV-2 infection 12. Serologic evidence of hepatitis C infection 13. Serologic evidence of acute or chronic active hepatitis B as measured by Core Ab positive and / or Surface Antibody antigen positive 14. Subjects with other autoimmune conditions (except compensated or treated autoimmune thyroid, celiac, alopecia, or vitiligo diseases) 15. Women who are pregnant (pregnancy testing during screening), breastfeeding, or planning pregnancy during the study period 16. Inadequate venous access to support leukapheresis 17. Any condition that in the opinion of the investigator(s) would preclude the subject from participating in a clinical trial. 18. Abnormal screening ECG that in the opinion of the investigator or sponsor would pose a safety risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline of Total Bilirubin | 5 months post first dose | Safety/tolerability outcomes - Total Bilirubin |
| Changes From Baseline of Creatinine | 5 months post first dose | Safety/tolerability outcomes - creatinine |
| Changes From Baseline of Aspartate Aminotransferase | 5 months post first dose | Safety/tolerability outcomes - Aspartate Aminotransferase |
| Changes From Baseline of Alanine Aminotransferase | 5 months post first dose | Safety/tolerability outcomes - Alanine Aminotransferase |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | At the Primary Analysis (when all the patients have completed their Day 150 visit) | Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose. |
| Number of Participants and Severity of Local i.v.-Site Reactions, | 5 months post first dose | Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | 5 months post first dose | The area under the stimulated C-peptide curve (AUC) over the first 4-hour period of a mixed meal glucose tolerance test is calculated using the trapezoidal rule that is a weighted sum of the C-peptide values over the 240 minutes. The AUC is normalized by dividing it with 240 mins, therefore, its unit is nmol/L. Missing C-peptide levels at any given timepoint is not imputed. In the calculation of the AUC when C-peptide levels are missing, a line is drawn from the last timepoint with a non-missing C-peptide to the next timepoint with non-missing C-peptide. |
| Changes From Baseline in HbA1c | 5 months post first dose | HbA1c is a blood test that is used to monitor blood glucose control in people with diabetes. HbA1c is short for glycated haemoglobin. The test is also sometimes called haemoglobin A1c. |
| Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay) | 5 months post first dose | CD8+ T cell Inhibition Assay is used to determine whether AVT001 corrects the defect of the dysfunctional Q/E CD8+ Treg pathway in T1D patients. More specifically, this assay detects the specific recognition between the TCR on patients' Q/E CD8+Treg cells and the common target structure, the HLA-E/Hsp60sp complex, expressed on the surface of the artificially established target cells. The % inhibition measures the function of down-regulation by Q/E CD8+ Tregs via comparing the % of inhibition of TH1 cells versus TB1 cells. By assessing the % inhibition of the TH1 cells of the patient's CD8+ T cells, the CD8+ T cell Inhibition Assay detects the specific recognition of the common target structure (HLA-E/Hsp60sp) on TH1 cells by the TCR on the patient's T cells to be tested. A negative value means the measured Q/E CD8+ Tregs completely lose its inhibition function, and the TH1 cells cultured with it happened to grow faster than the corresponding TB1 cells as its control. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVT001 (Treatment) Infusion of AVT001 (treatment)
AVT001: autologous dendritic cell therapy | 16 |
| Matched Placebo Infusion of AVT001-matched placebo
Placebo: matched placebo | 9 |
| Total | 25 |
Baseline characteristics
| Characteristic | AVT001 (Treatment) | Matched Placebo | Total |
|---|---|---|---|
| Age, Continuous | 26.5 years STANDARD_DEVIATION 9 | 26.2 years STANDARD_DEVIATION 6.2 | 26.4 years STANDARD_DEVIATION 8 |
| Age, Customized Age by Category <18 | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized Age by Category 18-<25 | 7 Participants | 4 Participants | 11 Participants |
| Age, Customized Age by Category 25-<40 | 6 Participants | 4 Participants | 10 Participants |
| Age, Customized Age by Category 40-<60 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 9 |
| other Total, other adverse events | 16 / 16 | 9 / 9 |
| serious Total, serious adverse events | 0 / 16 | 0 / 9 |
Outcome results
Primary
Changes From Baseline of Alanine Aminotransferase
Safety/tolerability outcomes - Alanine Aminotransferase
Time frame: 5 months post first dose
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline of Alanine Aminotransferase | -0.1 U/L | Standard Deviation 5.21 |
| Matched Placebo | Changes From Baseline of Alanine Aminotransferase | 1.1 U/L | Standard Deviation 3.26 |
Primary
Changes From Baseline of Aspartate Aminotransferase
Safety/tolerability outcomes - Aspartate Aminotransferase
Time frame: 5 months post first dose
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline of Aspartate Aminotransferase | -1.9 U/L | Standard Deviation 7.76 |
| Matched Placebo | Changes From Baseline of Aspartate Aminotransferase | 2.2 U/L | Standard Deviation 6.1 |
Primary
Changes From Baseline of Creatinine
Safety/tolerability outcomes - creatinine
Time frame: 5 months post first dose
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline of Creatinine | 1.9338 umol/L | Standard Deviation 7.51638 |
| Matched Placebo | Changes From Baseline of Creatinine | 0.4911 umol/L | Standard Deviation 5.48705 |
Primary
Changes From Baseline of Total Bilirubin
Safety/tolerability outcomes - Total Bilirubin
Time frame: 5 months post first dose
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline of Total Bilirubin | -0.114 umol/L | Standard Deviation 4.0603 |
| Matched Placebo | Changes From Baseline of Total Bilirubin | 0.000 umol/L | Standard Deviation 4.0103 |
Primary
Number of Participants and Severity of Local i.v.-Site Reactions,
Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported.
Time frame: 5 months post first dose
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVT001 (Treatment) | Number of Participants and Severity of Local i.v.-Site Reactions, | 0 Number of patients |
| Matched Placebo | Number of Participants and Severity of Local i.v.-Site Reactions, | 0 Number of patients |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose.
Time frame: At the Primary Analysis (when all the patients have completed their Day 150 visit)
Population: The safety (SAF) population is defined as all subjects who receive at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Nasal congestion | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Influenza like illness | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Nausea | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Oral papule | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Upper-airway cough syndrome | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Participants with Any TEAE | 9 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Neutrophil count decreased | 4 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Hyponatraemia | 3 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Cough | 3 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | White blood cell count decreased | 2 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Ear pain | 2 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Lymphocyte count decreased | 2 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Dizziness | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Anaemia | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood bicarbonate decreased | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood bilirubin increased | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Corona virus infection | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Fatigue | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Hypocalcaemia | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Pyrexia | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Chills | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Gastrooesophageal reflux disease | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Joint dislocation | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Gastroenteritis | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Non-cardiac chest pain | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Oropharyngeal pain | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Palpitations | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Sinusitis | 1 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Headache | 0 participants |
| AVT001 (Treatment) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood potassium decreased | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood bilirubin increased | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Gastroenteritis | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Nasal congestion | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Influenza like illness | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Corona virus infection | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Nausea | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Upper-airway cough syndrome | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Oral papule | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Fatigue | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Headache | 2 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Participants with Any TEAE | 6 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Hypocalcaemia | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Neutrophil count decreased | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Non-cardiac chest pain | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Hyponatraemia | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Pyrexia | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Cough | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Sinusitis | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | White blood cell count decreased | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Chills | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Ear pain | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Oropharyngeal pain | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Lymphocyte count decreased | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Gastrooesophageal reflux disease | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Dizziness | 2 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood potassium decreased | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Anaemia | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Joint dislocation | 0 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Blood bicarbonate decreased | 1 participants |
| Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Palpitations | 0 participants |
Secondary
Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay)
CD8+ T cell Inhibition Assay is used to determine whether AVT001 corrects the defect of the dysfunctional Q/E CD8+ Treg pathway in T1D patients. More specifically, this assay detects the specific recognition between the TCR on patients' Q/E CD8+Treg cells and the common target structure, the HLA-E/Hsp60sp complex, expressed on the surface of the artificially established target cells. The % inhibition measures the function of down-regulation by Q/E CD8+ Tregs via comparing the % of inhibition of TH1 cells versus TB1 cells. By assessing the % inhibition of the TH1 cells of the patient's CD8+ T cells, the CD8+ T cell Inhibition Assay detects the specific recognition of the common target structure (HLA-E/Hsp60sp) on TH1 cells by the TCR on the patient's T cells to be tested. A negative value means the measured Q/E CD8+ Tregs completely lose its inhibition function, and the TH1 cells cultured with it happened to grow faster than the corresponding TB1 cells as its control.
Time frame: 5 months post first dose
Population: The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVT001 (Treatment) | Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay) | Baseline | -11.2 Percent of Inhibition | Standard Deviation 9.9 |
| AVT001 (Treatment) | Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay) | Visit Day 150 | 9.3 Percent of Inhibition | Standard Deviation 24.9 |
| Matched Placebo | Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay) | Baseline | 3.5 Percent of Inhibition | Standard Deviation 7.1 |
| Matched Placebo | Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity (Potency Assay) | Visit Day 150 | 1.8 Percent of Inhibition | Standard Deviation 15.1 |
Secondary
Changes From Baseline in HbA1c
HbA1c is a blood test that is used to monitor blood glucose control in people with diabetes. HbA1c is short for glycated haemoglobin. The test is also sometimes called haemoglobin A1c.
Time frame: 5 months post first dose
Population: The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline in HbA1c | Baseline | 6.0375 % of glycated haemoglobin in the blood | Standard Deviation 0.73201 |
| AVT001 (Treatment) | Changes From Baseline in HbA1c | Visit Day 150 | 6.1500 % of glycated haemoglobin in the blood | Standard Deviation 0.84538 |
| Matched Placebo | Changes From Baseline in HbA1c | Baseline | 5.6556 % of glycated haemoglobin in the blood | Standard Deviation 0.67289 |
| Matched Placebo | Changes From Baseline in HbA1c | Visit Day 150 | 5.8222 % of glycated haemoglobin in the blood | Standard Deviation 0.8408 |
Secondary
Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT)
The area under the stimulated C-peptide curve (AUC) over the first 4-hour period of a mixed meal glucose tolerance test is calculated using the trapezoidal rule that is a weighted sum of the C-peptide values over the 240 minutes. The AUC is normalized by dividing it with 240 mins, therefore, its unit is nmol/L. Missing C-peptide levels at any given timepoint is not imputed. In the calculation of the AUC when C-peptide levels are missing, a line is drawn from the last timepoint with a non-missing C-peptide to the next timepoint with non-missing C-peptide.
Time frame: 5 months post first dose
Population: The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVT001 (Treatment) | Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | Baseline | 0.531 nmol/L | Standard Deviation 0.3628 |
| AVT001 (Treatment) | Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | Visit Day 150 | 0.518 nmol/L | Standard Deviation 0.4299 |
| Matched Placebo | Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | Baseline | 0.611 nmol/L | Standard Deviation 0.1776 |
| Matched Placebo | Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | Visit Day 150 | 0.472 nmol/L | Standard Deviation 0.1342 |