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)
Condition: Diabetes type1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The 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).
    

Detailed description: 
      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).
    

Intervention name(s): AG019 - Low Dose; Teplizumab; Placebo-AG019; Placebo-Teplizumab; AG019 - High Dose; AG019 - High Dose
Intervention type(s): Biological; Drug; Drug; Drug; Biological; Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: The phase 1b part of the study will enroll 4 sequential AG019 cohorts of up to 6 participants, in ascending dose cohorts and descending age cohorts. All participants in these cohorts will be treated with AG019 in an open label fashion.
The phase 2a part of the study will evaluate 2 cohorts of participants administered AG019 and teplizumab. The first 2 participants will be treated with active treatment in an open label fashion. Participants 3-12 will be randomized (4:1) to receive active treatment or placebo in a double-blind fashion.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment