Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1 (new-onset), Diabetes Mellitus, Insulin-Dependent (new-onset), new-onset T1DM, new-onset T1D, Diabetes Mellitus, Juvenile-Onset, Diabetes, Autoimmune, Aralast NP, Alpha-1 Antitrypsin, AAT
Brief summary
The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) that affects the cells thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD) and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in Part II (NCT01183455, Phase II Clinical Trial) will begin.
Detailed description
Researchers are interested in conducting this study to assess whether Aralast NP (AAT, Alpha-1 Antitrypsin ) will help slow the progression of T1DM. Part I of this study has two parts:-1a and -1b: Part 1a (Complete): An open-label, dose-escalation, PK, PD and safety study. Participants receive 12 intravenous (IV) infusions of Aralast NP. Infusions 1 through 6 are administered at 45 mg/kg/wk and infusions 7 through 12 are administered at 90 mg/kg/wk. Part Ia consists of two groups: * Subjects aged 16 - 35 years at enrollment with new-onset T1DM * Subjects aged 8 -15 years at enrollment with new-onset T1DM. Part 1b (study terminated prior to subject enrollment): An open-label, dose-escalation PK, PD and safety study in which participants receive 12 infusions of Aralast NP. Infusions 1 through 6 are administered at 90 mg/kg/wk and infusions 7 through 12 are administered at 180 mg/kg/wk. Part Ib consists of two groups: * Subjects aged 16 - 35 years at enrollment with new-onset T1DM * Subjects 8 - 15 years at enrollment with new-onset T1DM. Participants in Part Ib do not roll over into Part II (Refer to NCT01183455).
Interventions
BIOLOGICALAralast NP 45 mg dose
\- 45 mg/kg/week
BIOLOGICALAralast NP 90 mg dose
\- 90 mg/kg/week
BIOLOGICALAralast NP 180 mg dose
\- 180 mg/kg/week
Sponsors
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with T1DM within the past 100 days (of enrollment) * Positive for at least one diabetes-related autoantibody (Anti-GAD; Anti-insulin, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or ZnT8.) * Peak stimulated C-peptide level \> 0.2 pmol/mL following a mixed meal tolerance test (MMTT)
Exclusion criteria
* Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic, renal or immunodeficiency) * History of any bleeding or clotting factor deficiencies, or stroke * History of vascular disease or significant vascular abnormalities * Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV (human immunodeficiency virus) or toxoplasmosis * Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), or tuberculosis(TB) * Prior or current use of oral, inhaled or intranasal glucocorticoids, or any medication known to cause a significant, ongoing change in the course of T1DM or immunologic status * Prior treatment with Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to alpha 1-antitrypsin or human plasma-derived products * Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin * Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin) * Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation * IgA (immunoglobulin A) deficiency * Uncontrolled hypertension * Current life-threatening malignancy * Any condition that in the investigator's opinion may compromise study participation or may confound the interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52 | Week 52 | No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks. |
Countries
United States
Participant flow
Recruitment details
Twelve of the fifteen centers enrolled a total of 17 newly diagnosed (within 100 days of Visit 0 first low dose infusion) Type 1 Diabetes Mellitus participants.
Participants by arm
| Arm | Count |
|---|---|
| Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions. | 8 |
| Part 1a (Aralast NP)-Subjects 8-15 Yrs Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions. | 9 |
| Part 1b (Aralast NP)-Subjects Aged 18-35 Yrs Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Aralast NP 90 mg dose: - 90 mg/kg/week
Aralast NP 180 mg dose: - 180 mg/kg/week | 0 |
| Part 1b (Aralast NP)-Subjects 8-17 Yrs Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Aralast NP 90 mg dose: - 90 mg/kg/week
Aralast NP 180 mg dose: - 180 mg/kg/week | 0 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1a (Aralast NP)-Subjects 8-15 Yrs | Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 4 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Continuous | 10.7 years STANDARD_DEVIATION 2.2 | 20.6 years STANDARD_DEVIATION 5.7 | 15.4 years STANDARD_DEVIATION 6.6 |
| Region of Enrollment United States | 9 participants | 8 participants | 17 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 8 / 9 |
| serious Total, serious adverse events | 2 / 8 | 1 / 9 |
Outcome results
Primary
C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52
No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.
Time frame: Week 52
Population: Enrolled Sample