A first-in-human, open-label Phase 1b and a randomised, double-blind Phase 2a clinical trial in recent-onset type 1 diabetes with AG019 as monotherapy and in combination with teplizumab
Authors' conclusion
Oral delivery of AG019 was well tolerated and safe as monotherapy and in combination with teplizumab. AG019 was not shown to interfere with the safety profile of teplizumab and may have additional biological effects, including changes in preproinsulin-specific T cells. These preliminary data support continuing studies with this agent alone and in combination with teplizumab or other systemic immunotherapies in type 1 diabetes.
Study context
- Population
- Adults (18–42 years) and adolescents (12–17 years) with T1D diagnosed within 150 days, ≥1 autoantibody and stimulated peak C-peptide >0.2 nmol/l
- Participants
- 42 adults
- Comparison
- Oral AG019 monotherapy; AG019 in combination with teplizumab
- AG019 monotherapyn = 24
- AG019/teplizumabn = 18
- Primary endpoint
- Safety and tolerability based on incidence of treatment-emergent adverse events
- Follow-up
- Up to 6 months post treatment initiation
Methodological detailsfirst-in-human, double-blind (phase 2a), parallel
- First-in-human
- Double-blind (phase 2a)
- Parallel
Primary result
As reported in the abstract
Serious adverse events
0
Discontinued AG019 due to treatment-emergent adverse events
0
Secondary outcomes
Pharmacokinetics
- No systemic exposure to AG019 bacteria, proinsulin or human IL-10 was demonstrated
Metabolic variables, AG019 monotherapy (adults) · 6–12 months
- Metabolic variables stabilised up to 6 months (C-peptide, insulin use) or 12 months (HbA1c)
Metabolic and immune variables, AG019/teplizumab · 6–12 months
- All measured metabolic variables stabilised or improved up to 12 months
- CD8+ T cells with a partially exhausted phenotype significantly increased at 6 months
Preproinsulin-specific T cells
- Reduced frequency of preproinsulin-specific CD8+ T cells after monotherapy or combination therapy
Safety
Serious adverse events and discontinuations · up to 6 months
- Serious adverse events
- 0
- Discontinued AG019 due to treatment-emergent adverse events
- 0
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →