Recent-onset Type 1 Diabetes mellitus (T1D) MedDRA version: 21.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: AG019
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: Unknown
CAS Number: Unknown
Current Sponsor code: AG019
Other descriptive name: AG019
Concentration unit: m
Sponsors
Intrexon T1D Partners, LLC (IT1D)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or non-pregnant, non-lactating females, 18-40 years of age (both inclusive) or 12-17 years of age (both inclusive) - Diagnosis of diabetes according to the ADA recommended criteria - Evidence of auto-antibodies to at least 1 of the following ß-cell autoantigens: insulin, IA-2, GAD65, ZnT8 - Stimulated C-peptide measured during 4h Mixed Meal tolerance Test (MMTT) > 0.2 nmol/L - The first administration of AG019 should occur no later than 150 days post diagnosis - Body weight = 33kg - Willing and medically able to postpone live vaccine immunizations for at least 8 weeks after randomization - Ability and willingness of patients to participate fully in all aspects of this clinical study - Written informed consent obtained and documented - Willingness to use a continuous glucose monitoring device and willingness to comply with the protocol defined glucose monitoring - Total bilirubin =1.0 x upper limit of normal (ULN), Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =1.5 x ULN, =1,000 lymphocytes/µL, =1,000 polymorphonuclear neutrophils (PMN)/µL, =100,000 platelets/µL, Hgb =10 g/dL, Serum Creatinin =1.5 x ULN, eGFR =60 mL/min/1.73m², INR =0.1 above upper limit of normal, Absence of clinically significant age appropriate abnormalities on all other lab values, except for abnormalities directly attributable to T1D Are the trial subjects under 18? yes Number of subjects for this age range: 24 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Previous history of serious cytokine release syndrome to teplizumab or other humanized anti-CD3 monoclonal antibodies with no or minimal capacity to bind Fc receptors - Current use of any systemic antibiotics, except for the following: metronidazole (metronidazole), nalidixic acid (first generation quinolone), trimethoprim, sulfamethoxazole (sulfonamide) and/or a combination of both in a ratio 1/19 (sulfonamides) - Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomization - Participation in another investigational drug trial within 12 weeks prior to the first study drug intake and during participation in this study - History of recurrent infections, other autoimmune diseases, cardiac disease, malignancy, or any other (chronic) medical condition which, in the investigator’s opinion, could compromise participant safety - Documented history of human immunodeficiency virus (HIV), Hepatitis Virus Type C (HCV), Hepatitis Virus Type B (HBV) infection - Evidence of active infection with Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) - Untreated hypothyroidism or active Graves’ disease - Evidence of any active infection with the exception of superficial skin infections - Vaccination with live virus or organism within 8 weeks prior to randomization - Evidence of active or latent tuberculosis (TB) - Administration of anti-CD3 antibody in past year - Current therapy with any other anti-diabetic agents other than insulin (MDI, CSII or analogue). Current or planned therapy with experimental (i.e., unapproved) insulin - Use of medications known to influence glucose tolerance - Daily use of non-steroidal anti-inflammatory agents - Compromised GI mucosal integrity or motility, not attributable to T1D (i.e., recent diarrhea, gluten sensitive enteropathy, inflammatory bowel disease, irritable bowel syndrome), or current use of medications known to influence GI motility - Inability to swallow size 1 capsules - Alcohol or illicit drug consumption, which in the opinion of the investigator, may interfere with the patient’s ability to comply with the study procedures - Active psychiatric problems, which in the opinion of the investigator, may interfere with the patient’s ability to comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of different doses of AG019 alone as well as in association with teplizumab.;Primary end point(s): Analysis of the incidence of treatment-emergent adverse events (TEAEs) collected up to the 6-month follow-up visit. ;Timepoint(s) of evaluation of this end point: Cohorts 1-4 (AG019 only): Study day 1, 4, 7, 12, 28, 56, 90, 180 Cohorts 5-6 (AG019 + teplizumab): Study day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 28, 56, 90, 180;Secondary Objective: To obtain pharmacodynamics (PD) data of AG019 alone as well as AG019 in association with teplizumab To determine the potential presence of sAGX0407 or its secreted proteins in systemic circulation (safety – systemic exposure) and the presence of L. lactis bacteria in fecal excretion (local exposure): pharmacokinetic (PK) profile | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The PD activity of the study drug(s) will be assessed by measurement of biomarkers in blood and serum samples. Relevant parameters will be assessed, including immune markers for effect, relevant T1D parameters and relevant cytokines. Following parameters will be assessed for analysis of systemic and local exposure to L. lactis (PK profile): • Presence of live L. lactis clinical strain bacteria in whole blood • Measurable serum levels of hIL-10 and hPINS • Presence of L. lactis clinical strain bacteria in fecal excretion Safety information collected at all other time points will be assessed as secondary end points. ;Timepoint(s) of evaluation of this end point: PD: Study day1, 12, 56, 180, 270 and 360 PK: Study day 12, 56 and 90 | — |
Countries
Belgium, United States
Contacts
Public ContactSven Blomme
Intrexon Actobiotics NV, d/b/a ActoBio Therapeutics
Outcome results
None listed