Title
A Study to Assess the Safety and Tolerability of Different Doses of AG019 Administered Alone or in Combination With Teplizumab in Participants With Recent-onset Diagnosed Type 1 Diabetes (T1D)
A Prospective, Multi-center, Phase 1b/2a Study to Assess the Safety and Tolerability of Different Doses of AG019 Administered Alone or in Association With Teplizumab in Patients With Clinical Recent-onset Type 1 Diabetes Mellitus (T1D)
Phase
Phase 1/Phase 2Lead Sponsor
IntrexonStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Diabetes Mellitus, Type 1 ...Intervention/Treatment
AG019 - Low Dose Teplizumab Placebo-AG019 Placebo-Teplizumab AG019 - High Dose AG019 - High DoseStudy Participants
45The purpose of this study is to assess the safety and tolerability of different doses of AG019 administered alone or in combination with teplizumab in participants with recent-onset type 1 diabetes (T1D).
This Phase 1b/2a, multi-center study will be conducted in participants with clinical recent-onset type 1 diabetes (T1D).
The primary objective of this study is to assess the safety and tolerability of different doses of AG019 alone as well as AG019 in combination with teplizumab. The secondary objectives of this study are: to obtain pharmacodynamic (PD) data of AG019 alone as well as AG019 in combination with teplizumab; and to determine the potential presence of AG019 in systemic circulation (safety - systemic exposure) and the presence of L. lactis bacteria in fecal excretion (local exposure): Pharmacokinetic (PK) profile.
This study consists of 2 phases:
Phase 1b: this open-label part of the study will investigate the safety and tolerability of 2 different doses of AG019 in 2 age groups (18-40 years of age and 12-17 years of age).
Phase 2a: this randomized, double-blind part of the study will investigate the safety and tolerability of AG019, in combination with teplizumab, in 2 age groups (18-40 years of age and 12-17 years of age).
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)
Daily IV infusions of Teplizumab during the first 12 days of AG019 treatment. Total cumulative dose is approximately 17mg (dose calculation based on body surface area).
Formulated identically to AG019 with the active ingredient removed.
Formulated identically to teplizumab with the active ingredient removed.
Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks
Solid, orally administered capsule - 6 capsules per day for 8 weeks.
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 American Diabetes Association (ADA) recommended criteria Evidence of auto-antibodies to at least 1 β-cell autoantigen 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 of diabetes Body weight ≥ 33kg Written informed consent obtained and documented (participant, parent, guardian as applicable) 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. (Participants enrolled in the second phase of the trial in either Combination Cohort 1 or Combination Cohort 2, only) 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) 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. Patients on therapy for type 2 diabetes (e.g. metformin) should stop their therapy in order to be eligible for study participation. 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 Positive result of SARS-Cov2 PCR test at screening or within 3 days before randomization
| Event Type | Organ System | Event Term | AG019 Cohort 1 - Low (Single) Dose/Adults | AG019 Cohort 1 - Low (Repeat) Dose/Adults | AG019 Cohort 2 - High (Single) Dose/Adults | AG019 Cohort 2 - High (Repeat) Dose/Adults | AG019 Cohort 3 - Low (Single) Dose/Adolescents | AG019 Cohort 3 - Low (Repeat) Dose/Adolescents | AG019 Cohort 4 - High (Single) Dose/Adolescents | AG019 Cohort 4 - High (Repeat) Dose/Adolescents | Combination Cohort 1 - Active AG019/Teplizumab - Adults | Combination Cohort 1 - AG019-placebo/Teplizumab-placebo - Adults | Combination Cohort 2 - Active AG019/Teplizumab - Adolescents | Combination Cohort 2 - AG019-placebo/Teplizumab-placebo - Adolescents |
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Treatment-emergent adverse events assessed by the investigator, review of lab reports and information provided by the participant during site visits and/or participant diary with AG019 alone or with teplizumab
The presence of live L. lactis bacteria in blood will be assessed by plating
The presence of L. lactis-secreted hPINS or hIL-10 in the blood will be assessed by ELISA (enzyme-linked immunosorbent assay)
The presence of L. lactis (live or dead) in feces will be assessed by Q-PCR (quantitative real-time polymerase chain reaction)
MMTT-stimulated 2-hour C-peptide AUC was defined as the mean area under the C-peptide level time curve over the 2-hour period divided by the duration after a mixed-meal tolerance test.
Incidence of all reported TEAE up to the 12-month follow-up visit. The TEAE are counted once within each patient on the preferred term level.
