Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes Mellitus, Alpha1-Proteinase Inhibitor, Beta Cell, Alpha1-Antitrypsin
Brief summary
This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed enrollment will be opened to the child cohort. The purpose of this study is to evaluate the safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
Interventions
BIOLOGICAL180 mg/kg Alpha1-PI
BIOLOGICAL90 mg/kg Alpha1-PI
BIOLOGICALPlacebo
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T1DM according to the ADA criteria. * Current use of injected insulin therapy and one positive result on testing for any of the following antibodies (If not currently on insulin therapy, must have positive result for at least two of the below antibodies): * Anti-islet-cell antibodies (islet cell antigen 512, insulinoma associated protein 2), * Anti-glutamic acid decarboxylase antibodies, or * Anti-insulin antibodies (unless received insulin therapy for \> 7 days). * Body Mass Index (BMI) ≤ 28 kg/m2 for adults (≥ 20 years of age) OR ≤ 90th percentile in accordance with the Centers for Disease Control BMI assessment for children and teens (2 through 19 years old).
Exclusion criteria
* History of or current diabetic retinopathy, neuropathy, or nephropathy. * Known thrombophilia or history of thrombosis. * Malignant disease (including malignant melanoma; however, other forms of skin cancer are allowed) within five years of randomization. * Active Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, or Human Immunodeficiency Virus infection. * History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s). * Known selective or severe Immunoglobulin A deficiency. * Elevated liver enzymes (aspartate transaminase, alanine aminotransferase, and alkaline phosphatase) equal to or greater than 2.5 times the upper limit of normal. * Therapy with exenatide or any other agents that stimulate pancreatic β cell regeneration or insulin secretion, or any antidiabetic agents (oral or parenteral) other than insulin within one month prior to screening. * Use of omega-3 fatty acid supplements, including fish oil, within seven days prior to screening. * Current or planned therapy with inhaled insulin, if it becomes available. * Chronic use of systemic steroids, with the exception of inhaled steroids, above a stable dose equivalent to 5 mg/day prednisone (e.g., 10 mg every 2 days) within 4 weeks prior to randomization. It is recommended to maintain the same dose throughout the study. (Note: Subjects with autoimmune conditions (i.e., asthma) necessitating treatment with systemic short-term corticosteroids and administered a rapid taper are eligible per protocol with the caveat that the tapering is complete or decreased to the minimum requirement (i.e., 5 mg/day) at least 1 week prior to the Baseline visit (when randomization occurs) to ensure the subject is stable. For longer term steroid usage, please consult the Grifols Medical Monitor before considering the subject for study participation.) * Treatment with immunosuppressants or cytostatic agents within 6 months of randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink) | C-peptide concentration during MMTT with high protein energy drink. Dose for time frame refers to intake of high protein energy drink. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink) | — |
| Change From Baseline for HbA1c Levels | Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104 | — |
| Number of Subjects With Overall Severe Hypoglycemic Episodes | 104 weeks | Severe hypoglycemia defined according the ADA Workgroup on Hypoglycemia definition, as follows: An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions. |
| Change From Baseline for Mean Daily Insulin Dose Requirements | Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104 | — |
| Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104 | For each visit, the mean daily glucose levels were calculated over the previous 3-7 days prior to the study visit from blood glucose levels recorded daily prior to meals and bedtime. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
180 mg/kg Alpha1-PI | 15 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks 180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.
180 mg/kg Alpha1-PI | 16 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
90 mg/kg Alpha1-PI | 15 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
90 mg/kg Alpha1-PI | 15 |
| Placebo Weekly infusions of placebo for 13 or 26 weeks.
Placebo | 15 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study termination | 6 | 5 | 4 | 6 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 4 | 1 | 1 |
Baseline characteristics
| Characteristic | Alpha1-PI 180 mg/kg/wk, 26 Weeks | Total | Placebo | 90 mg/kg/wk Alpha1-PI, 13 Weeks | 90 mg/kg/wk Alpha1-PI, 26 Weeks | 180 mg/kg/wk Alpha1-PI, 13 Weeks |
|---|---|---|---|---|---|---|
| Age, Customized 12 - 17 years | 7 Participants | 34 Participants | 6 Participants | 7 Participants | 7 Participants | 7 Participants |
| Age, Customized 18 - 35 years | 6 Participants | 29 Participants | 7 Participants | 5 Participants | 5 Participants | 6 Participants |
| Age, Customized 6 - 11 years | 2 Participants | 13 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 9 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 67 Participants | 15 Participants | 13 Participants | 12 Participants | 15 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 71 Participants | 15 Participants | 13 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Female | 6 Participants | 31 Participants | 4 Participants | 4 Participants | 9 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 45 Participants | 11 Participants | 11 Participants | 6 Participants | 8 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 / 15 | 1 / 16 | 0 / 14 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 10 / 15 | 8 / 16 | 11 / 14 | 13 / 15 | 11 / 15 |
| serious Total, serious adverse events | 0 / 15 | 3 / 16 | 0 / 14 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
C-peptide concentration during MMTT with high protein energy drink. Dose for time frame refers to intake of high protein energy drink.
Time frame: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Population: Twelve subjects prematurely discontinued from the study prior to Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | -32.357 min*nmol/L | Standard Deviation 27.7184 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | -25.171 min*nmol/L | Standard Deviation 28.945 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | -21.682 min*nmol/L | Standard Deviation 24.5787 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | -34.393 min*nmol/L | Standard Deviation 25.6837 |
| Placebo | Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) | -16.909 min*nmol/L | Standard Deviation 19.1278 |
Secondary
Change From Baseline for HbA1c Levels
Time frame: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Population: Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 14 | -0.68 percentage of change from baseline | Standard Deviation 2.108 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 104 | -0.76 percentage of change from baseline | Standard Deviation 1.419 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 87 | -0.54 percentage of change from baseline | Standard Deviation 1.31 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 39 | -0.58 percentage of change from baseline | Standard Deviation 2.098 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 27 | -0.67 percentage of change from baseline | Standard Deviation 1.953 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 52 | -0.47 percentage of change from baseline | Standard Deviation 1.383 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for HbA1c Levels | Week 69 | -0.01 percentage of change from baseline | Standard Deviation 1.63 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 69 | -0.18 percentage of change from baseline | Standard Deviation 2.529 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 52 | -0.55 percentage of change from baseline | Standard Deviation 3.437 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 27 | -1.38 percentage of change from baseline | Standard Deviation 2.799 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 14 | -1.75 percentage of change from baseline | Standard Deviation 2.543 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 87 | -0.38 percentage of change from baseline | Standard Deviation 3.035 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 39 | -0.78 percentage of change from baseline | Standard Deviation 3.043 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 104 | -0.69 percentage of change from baseline | Standard Deviation 2.49 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 52 | -0.25 percentage of change from baseline | Standard Deviation 1.399 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 14 | -1.16 percentage of change from baseline | Standard Deviation 1.683 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 27 | -0.74 percentage of change from baseline | Standard Deviation 2.263 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 39 | -0.40 percentage of change from baseline | Standard Deviation 1.495 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 69 | 0.09 percentage of change from baseline | Standard Deviation 1.197 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 87 | 0.30 percentage of change from baseline | Standard Deviation 2.147 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for HbA1c Levels | Week 104 | 0.28 percentage of change from baseline | Standard Deviation 1.987 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 39 | -0.55 percentage of change from baseline | Standard Deviation 2.798 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 69 | -0.33 percentage of change from baseline | Standard Deviation 2.532 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 27 | -0.89 percentage of change from baseline | Standard Deviation 2.74 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 104 | -0.10 percentage of change from baseline | Standard Deviation 2.89 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 87 | -0.26 percentage of change from baseline | Standard Deviation 2.608 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 14 | -1.45 percentage of change from baseline | Standard Deviation 1.812 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for HbA1c Levels | Week 52 | -0.51 percentage of change from baseline | Standard Deviation 2.504 |
| Placebo | Change From Baseline for HbA1c Levels | Week 39 | -1.52 percentage of change from baseline | Standard Deviation 2.473 |
| Placebo | Change From Baseline for HbA1c Levels | Week 104 | -1.36 percentage of change from baseline | Standard Deviation 2.155 |
| Placebo | Change From Baseline for HbA1c Levels | Week 87 | -0.89 percentage of change from baseline | Standard Deviation 3.011 |
| Placebo | Change From Baseline for HbA1c Levels | Week 69 | -1.37 percentage of change from baseline | Standard Deviation 3.004 |
| Placebo | Change From Baseline for HbA1c Levels | Week 27 | -2.52 percentage of change from baseline | Standard Deviation 2.439 |
| Placebo | Change From Baseline for HbA1c Levels | Week 14 | -2.64 percentage of change from baseline | Standard Deviation 2.452 |
| Placebo | Change From Baseline for HbA1c Levels | Week 52 | -1.52 percentage of change from baseline | Standard Deviation 2.805 |
Secondary
Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime
For each visit, the mean daily glucose levels were calculated over the previous 3-7 days prior to the study visit from blood glucose levels recorded daily prior to meals and bedtime.
Time frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Population: Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 104 | 2.545 mmol/L | Standard Deviation 0 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 39 | 1.347 mmol/L | Standard Deviation 2.0674 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 4 | 2.343 mmol/L | Standard Deviation 2.3942 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 52 | 2.995 mmol/L | Standard Deviation 1.6703 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 87 | 3.354 mmol/L | Standard Deviation 2.955 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 14 | 2.812 mmol/L | Standard Deviation 2.5953 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 69 | 2.182 mmol/L | Standard Deviation 1.3352 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 27 | 1.782 mmol/L | Standard Deviation 1.7921 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 2 | 2.223 mmol/L | Standard Deviation 3.6282 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 69 | 18.224 mmol/L | Standard Deviation 41.1471 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 52 | 3.067 mmol/L | Standard Deviation 2.916 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 27 | 2.252 mmol/L | Standard Deviation 2.8173 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 39 | 3.848 mmol/L | Standard Deviation 2.2236 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 14 | 2.200 mmol/L | Standard Deviation 2.1283 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 104 | 1.867 mmol/L | Standard Deviation 2.4532 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 4 | 1.856 mmol/L | Standard Deviation 2.475 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 2 | 2.379 mmol/L | Standard Deviation 2.7555 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 87 | 3.101 mmol/L | Standard Deviation 2.3859 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 52 | 3.242 mmol/L | Standard Deviation 3.1636 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 2 | 1.848 mmol/L | Standard Deviation 1.1257 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 4 | 2.106 mmol/L | Standard Deviation 1.3144 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 14 | 2.852 mmol/L | Standard Deviation 3.0376 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 27 | 2.446 mmol/L | Standard Deviation 3.2355 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 39 | 4.471 mmol/L | Standard Deviation 2.739 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 69 | 4.324 mmol/L | Standard Deviation 4.4173 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 87 | 3.234 mmol/L | Standard Deviation 2.1516 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 104 | 2.390 mmol/L | Standard Deviation 1.5429 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 27 | 3.471 mmol/L | Standard Deviation 3.1043 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 52 | 2.723 mmol/L | Standard Deviation 4.3749 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 14 | 2.337 mmol/L | Standard Deviation 3.9732 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 69 | 3.677 mmol/L | Standard Deviation 3.7397 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 4 | 0.759 mmol/L | Standard Deviation 1.0403 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 104 | 2.283 mmol/L | Standard Deviation 6.1064 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 87 | 3.835 mmol/L | Standard Deviation 3.676 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 2 | 0.578 mmol/L | Standard Deviation 1.6824 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 39 | 3.681 mmol/L | Standard Deviation 4.0469 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 2 | 0.178 mmol/L | Standard Deviation 1.5195 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 27 | 0.577 mmol/L | Standard Deviation 2.1475 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 52 | 0.616 mmol/L | Standard Deviation 2.1868 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 14 | -0.053 mmol/L | Standard Deviation 1.4368 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 39 | 1.421 mmol/L | Standard Deviation 2.1779 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 104 | 2.431 mmol/L | Standard Deviation 1.4519 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 87 | 4.863 mmol/L | Standard Deviation 2.5173 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 69 | 1.467 mmol/L | Standard Deviation 4.2254 |
| Placebo | Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime | Week 4 | -0.158 mmol/L | Standard Deviation 1.4665 |
Secondary
Change From Baseline for Mean Daily Insulin Dose Requirements
Time frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Population: Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 27 | -0.040 U/kg/day | Standard Deviation 0.2313 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 69 | 0.192 U/kg/day | Standard Deviation 0.5491 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 14 | -0.239 U/kg/day | Standard Deviation 0.2301 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 4 | -0.147 U/kg/day | Standard Deviation 0.1405 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 104 | 0.491 U/kg/day | Standard Deviation 0 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 87 | 0.517 U/kg/day | Standard Deviation 0 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 52 | 0.226 U/kg/day | Standard Deviation 0.5861 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 2 | -0.146 U/kg/day | Standard Deviation 0.2044 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 39 | -0.040 U/kg/day | Standard Deviation 0.3222 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 87 | 0.164 U/kg/day | Standard Deviation 0.5377 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 104 | -0.168 U/kg/day | Standard Deviation 0.465 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 2 | -0.141 U/kg/day | Standard Deviation 0.2143 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 14 | -0.305 U/kg/day | Standard Deviation 0.1406 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 27 | -0.033 U/kg/day | Standard Deviation 0.431 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 39 | 0.146 U/kg/day | Standard Deviation 0.79 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 52 | -0.037 U/kg/day | Standard Deviation 0.872 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 69 | 0.213 U/kg/day | Standard Deviation 0.6097 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 4 | -0.264 U/kg/day | Standard Deviation 0.1456 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 87 | 0.247 U/kg/day | Standard Deviation 0.6591 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 27 | -0.090 U/kg/day | Standard Deviation 0.2117 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 69 | 0.142 U/kg/day | Standard Deviation 0.5981 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 39 | -0.089 U/kg/day | Standard Deviation 0.2099 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 104 | 0.307 U/kg/day | Standard Deviation 0.3772 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 52 | -0.055 U/kg/day | Standard Deviation 0.218 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 4 | -0.201 U/kg/day | Standard Deviation 0.2058 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 14 | -0.092 U/kg/day | Standard Deviation 0.1442 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 2 | -0.205 U/kg/day | Standard Deviation 0.2194 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 14 | -0.239 U/kg/day | Standard Deviation 0.143 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 2 | -0.274 U/kg/day | Standard Deviation 0.1416 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 52 | 0.214 U/kg/day | Standard Deviation 0.5898 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 27 | -0.138 U/kg/day | Standard Deviation 0.2321 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 87 | 0.086 U/kg/day | Standard Deviation 0.5132 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 39 | -0.158 U/kg/day | Standard Deviation 0.2552 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 104 | -0.015 U/kg/day | Standard Deviation 0.5626 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 4 | -0.220 U/kg/day | Standard Deviation 0.1744 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 69 | 0.016 U/kg/day | Standard Deviation 0.7005 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 104 | 0.303 U/kg/day | Standard Deviation 0 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 2 | -0.158 U/kg/day | Standard Deviation 0.2828 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 4 | -0.150 U/kg/day | Standard Deviation 0.2788 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 14 | -0.118 U/kg/day | Standard Deviation 0.1114 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 27 | -0.135 U/kg/day | Standard Deviation 0.0607 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 39 | -0.150 U/kg/day | Standard Deviation 0.11 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 52 | -0.320 U/kg/day | Standard Deviation 0.2906 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 69 | -0.011 U/kg/day | Standard Deviation 0.2858 |
| Placebo | Change From Baseline for Mean Daily Insulin Dose Requirements | Week 87 | -0.044 U/kg/day | Standard Deviation 0.4264 |
Secondary
Change From Baseline for MMTT Stimulated C-peptide 2h AUC
Time frame: Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Population: Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 27 | -30.709 min*nmol/L | Standard Deviation 21.2821 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 14 | -19.396 min*nmol/L | Standard Deviation 23.7789 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 39 | -28.500 min*nmol/L | Standard Deviation 37.6682 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 69 | -45.316 min*nmol/L | Standard Deviation 27.1563 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 87 | -42.487 min*nmol/L | Standard Deviation 31.9418 |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 104 | -29.687 min*nmol/L | Standard Deviation 25.5941 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 87 | -43.012 min*nmol/L | Standard Deviation 23.2403 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 104 | -44.314 min*nmol/L | Standard Deviation 28.0612 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 14 | -0.444 min*nmol/L | Standard Deviation 18.8595 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 39 | -17.664 min*nmol/L | Standard Deviation 26.1729 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 69 | -42.014 min*nmol/L | Standard Deviation 15.7239 |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 27 | -17.826 min*nmol/L | Standard Deviation 21.0462 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 69 | -27.023 min*nmol/L | Standard Deviation 28.692 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 87 | -34.590 min*nmol/L | Standard Deviation 21.6148 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 14 | 4.427 min*nmol/L | Standard Deviation 33.222 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 39 | -23.342 min*nmol/L | Standard Deviation 21.6945 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 27 | 6.537 min*nmol/L | Standard Deviation 56.1336 |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 104 | -32.980 min*nmol/L | Standard Deviation 18.2765 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 69 | -39.735 min*nmol/L | Standard Deviation 23.3488 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 27 | -23.082 min*nmol/L | Standard Deviation 22.3027 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 39 | -36.580 min*nmol/L | Standard Deviation 20.7765 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 104 | -39.908 min*nmol/L | Standard Deviation 26.4652 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 87 | -47.496 min*nmol/L | Standard Deviation 23.7717 |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 14 | -12.725 min*nmol/L | Standard Deviation 20.2051 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 87 | -32.561 min*nmol/L | Standard Deviation 20.0826 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 104 | -26.586 min*nmol/L | Standard Deviation 20.6803 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 39 | -10.808 min*nmol/L | Standard Deviation 20.0078 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 27 | -1.411 min*nmol/L | Standard Deviation 26.855 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 69 | -16.744 min*nmol/L | Standard Deviation 21.8947 |
| Placebo | Change From Baseline for MMTT Stimulated C-peptide 2h AUC | Week 14 | 3.317 min*nmol/L | Standard Deviation 21.1784 |
Secondary
Number of Subjects With Overall Severe Hypoglycemic Episodes
Severe hypoglycemia defined according the ADA Workgroup on Hypoglycemia definition, as follows: An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions.
Time frame: 104 weeks
Population: Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 1 episode | 1 Participants |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 3 episodes | 0 Participants |
| Alpha1-PI 180 mg/kg/wk, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 2 episodes | 0 Participants |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 2 episodes | 0 Participants |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 1 episode | 2 Participants |
| 180 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 3 episodes | 0 Participants |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 2 episodes | 0 Participants |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 1 episode | 0 Participants |
| 90 mg/kg/wk Alpha1-PI, 26 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 3 episodes | 1 Participants |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 1 episode | 0 Participants |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 3 episodes | 0 Participants |
| 90 mg/kg/wk Alpha1-PI, 13 Weeks | Number of Subjects With Overall Severe Hypoglycemic Episodes | 2 episodes | 0 Participants |
| Placebo | Number of Subjects With Overall Severe Hypoglycemic Episodes | 2 episodes | 0 Participants |
| Placebo | Number of Subjects With Overall Severe Hypoglycemic Episodes | 1 episode | 1 Participants |
| Placebo | Number of Subjects With Overall Severe Hypoglycemic Episodes | 3 episodes | 0 Participants |