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)

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03751007

Enrollment

Registered

2018-11-23

Start date

2018-10-24

Completion date

2021-10-13

Last updated

2023-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes type1

Brief 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).

Interventions

BIOLOGICALAG019 - Low Dose

Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)

DRUGTeplizumab

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).

DRUGPlacebo-AG019

Formulated identically to AG019 with the active ingredient removed.

DRUGPlacebo-Teplizumab

Formulated identically to teplizumab with the active ingredient removed.

BIOLOGICALAG019 - High Dose

Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

For the randomized participants in the combination cohorts, blinding will be accomplished by arranging for AG019 and placebo components as well as teplizumab and placebo components to have identical packaging.

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.

Eligibility

Sex/Gender

ALL

Age

12 Years to 40 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Treatment-emergent Adverse Events (TEAE)	up to 6 months	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

Secondary

Measure	Time frame	Description
AG019 in Systemic Circulation	Up to 3 months after initiation of the treatment	The presence of live L. lactis bacteria in blood will be assessed by plating
L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	Up to 3 months after initiation of the treatment	The presence of L. lactis-secreted hPINS or hIL-10 in the blood will be assessed by ELISA (enzyme-linked immunosorbent assay)
AG019 in Feces	Up to 8 days after completion of the treatment	The presence of L. lactis (live or dead) in feces will be assessed by Q-PCR (quantitative real-time polymerase chain reaction)
C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	up to 12 months	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.

Other

Measure	Time frame	Description
Incidence of Treatment Emergent Adverse Events up to 12 Months	Up to 12 months from screening	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.

Countries

Belgium, United States

Participant flow

Recruitment details

AG019 monotherapy cohorts: a total of 8 single dose patients and 19 repeat dose patients. AG019/teplizumab combination cohorts: a total of 18 patients

Pre-assignment details

* 18-40y, or 12-17y * diagnosis of diabetes according to ADA criteria * positive for at least 1 T1D autoantibody * treatment to be started within 150 days of diagnosis * greater than 0.2 nmol/L of C-peptide following mixed meal tolerance test * No active infections

Participants by arm

Arm	Count
AG019 Cohort 1 - Low (Single) Dose/Adults AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)	2
AG019 Cohort 1 - Low (Repeat) Dose/Adults AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)	5
AG019 Cohort 2 - High (Single) Dose/Adults AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)	2
AG019 Cohort 2 - High (Repeat) Dose/Adults AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)	5
AG019 Cohort 3 - Low (Single) Dose/Adolescents AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)	2
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)	4
AG019 Cohort 4 - High (Single) Dose/Adolescents AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)	2
AG019 Cohort 4 - High (Repeat) Dose/Adolescents AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)	5
Combination Cohort 1 - Active AG019/Teplizumab - Adults Teplizumab: 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). AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks	10
Combination Cohort 1 - AG019-placebo/Teplizumab-placebo - Adults Placebo-AG019: Formulated identically to AG019 with the active ingredient removed. Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.	2
Combination Cohort 2 - Active AG019/Teplizumab - Adolescents Teplizumab: 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). AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks	5
Combination Cohort 2 - AG019-placebo/Teplizumab-placebo - Adolescents Placebo-AG019: Formulated identically to AG019 with the active ingredient removed. Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.	1
Total	45

Baseline characteristics

Characteristic	Total	Combination Cohort 2 - AG019-placebo/Teplizumab-placebo - Adolescents	Combination Cohort 2 - Active AG019/Teplizumab - Adolescents	Combination Cohort 1 - AG019-placebo/Teplizumab-placebo - Adults	Combination Cohort 1 - Active AG019/Teplizumab - Adults	AG019 Cohort 1 - Low (Single) Dose/Adults	AG019 Cohort 4 - High (Repeat) Dose/Adolescents	AG019 Cohort 4 - High (Single) Dose/Adolescents	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
Age, Continuous	20.0 years STANDARD_DEVIATION 8.6	12.0 years STANDARD_DEVIATION 0	14.0 years STANDARD_DEVIATION 1.1	29.0 years STANDARD_DEVIATION 5.7	26.5 years STANDARD_DEVIATION 6.7	38.0 years STANDARD_DEVIATION 5.7	14.0 years STANDARD_DEVIATION 1.9	17.0 years STANDARD_DEVIATION 0	26.0 years STANDARD_DEVIATION 8.9	19.5 years STANDARD_DEVIATION 2.1	22.0 years STANDARD_DEVIATION 7.4	16.5 years STANDARD_DEVIATION 0.7	14.0 years STANDARD_DEVIATION 2.2
Autoantibody positivity - GAD65 Missing	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Autoantibody positivity - GAD65 Negative	3 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Autoantibody positivity - GAD65 Positive	39 Participants	1 Participants	3 Participants	2 Participants	10 Participants	1 Participants	5 Participants	1 Participants	5 Participants	2 Participants	5 Participants	1 Participants	3 Participants
Autoantibody positivity - IA-2 Missing	8 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Autoantibody positivity - IA-2 Negative	16 Participants	0 Participants	1 Participants	1 Participants	5 Participants	1 Participants	2 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	2 Participants
Autoantibody positivity - IA-2 Positive	21 Participants	1 Participants	4 Participants	1 Participants	3 Participants	0 Participants	2 Participants	0 Participants	2 Participants	1 Participants	4 Participants	1 Participants	2 Participants
Autoantibody positivity - Insulin Missing	13 Participants	0 Participants	1 Participants	0 Participants	5 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants
Autoantibody positivity - Insulin Negative	19 Participants	0 Participants	3 Participants	1 Participants	5 Participants	1 Participants	2 Participants	1 Participants	2 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Autoantibody positivity - Insulin Positive	13 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	3 Participants	1 Participants	3 Participants	0 Participants	1 Participants
Autoantibody positivity - ZnT8 Missing	18 Participants	1 Participants	2 Participants	2 Participants	3 Participants	1 Participants	1 Participants	2 Participants	3 Participants	0 Participants	1 Participants	2 Participants	0 Participants
Autoantibody positivity - ZnT8 Negative	7 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Autoantibody positivity - ZnT8 Positive	20 Participants	0 Participants	3 Participants	0 Participants	5 Participants	1 Participants	3 Participants	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	3 Participants
Baseline HbA1c	6.86 percent STANDARD_DEVIATION 1.44	8.40 percent	7.14 percent STANDARD_DEVIATION 2.43	7.35 percent STANDARD_DEVIATION 3.04	6.92 percent STANDARD_DEVIATION 1.42	—	6.28 percent STANDARD_DEVIATION 0.89	—	6.38 percent STANDARD_DEVIATION 0.56	—	7.00 percent STANDARD_DEVIATION 1.57	—	6.40 percent STANDARD_DEVIATION 0.51
Baseline IDAA1c	8.55 units on a scale' STANDARD_DEVIATION 2.02	10.640 units on a scale'	9.605 units on a scale' STANDARD_DEVIATION 2.583	8.530 units on a scale' STANDARD_DEVIATION 4.54	8.412 units on a scale' STANDARD_DEVIATION 1.725	—	8.392 units on a scale' STANDARD_DEVIATION 2.47	—	7.385 units on a scale' STANDARD_DEVIATION 1.303	—	8.248 units on a scale' STANDARD_DEVIATION 2.369	—	9.090 units on a scale' STANDARD_DEVIATION 1.093
Baseline serological cytomegalovirus positivity Missing	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Baseline serological cytomegalovirus positivity Negative	37 Participants	1 Participants	4 Participants	1 Participants	5 Participants	2 Participants	5 Participants	2 Participants	5 Participants	2 Participants	5 Participants	2 Participants	3 Participants
Baseline serological cytomegalovirus positivity Positive	7 Participants	0 Participants	0 Participants	1 Participants	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Baseline serological Epstein-Barr virus positivity Negative	31 Participants	1 Participants	4 Participants	0 Participants	4 Participants	2 Participants	4 Participants	2 Participants	2 Participants	2 Participants	4 Participants	2 Participants	4 Participants
Baseline serological Epstein-Barr virus positivity Positive	14 Participants	0 Participants	1 Participants	2 Participants	6 Participants	0 Participants	1 Participants	0 Participants	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants	1 Participants	5 Participants	2 Participants	10 Participants	2 Participants	5 Participants	1 Participants	5 Participants	1 Participants	4 Participants	2 Participants	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Fasting C-peptide	0.65 nmol/L STANDARD_DEVIATION 0.46	0.16 nmol/L	0.25 nmol/L STANDARD_DEVIATION 0.07	0.36 nmol/L STANDARD_DEVIATION 0.22	0.18 nmol/L STANDARD_DEVIATION 0.13	—	0.27 nmol/L STANDARD_DEVIATION 0.14	—	0.27 nmol/L STANDARD_DEVIATION 0.15	—	0.38 nmol/L STANDARD_DEVIATION 0.19	—	0.33 nmol/L STANDARD_DEVIATION 0.08
Insulin required at baseline No	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Insulin required at baseline Yes	43 Participants	1 Participants	5 Participants	2 Participants	10 Participants	1 Participants	5 Participants	2 Participants	5 Participants	2 Participants	4 Participants	2 Participants	4 Participants
Mean 2H C-peptide AUC	0.63 nmol/L STANDARD_DEVIATION 0.32	0.000 nmol/L STANDARD_DEVIATION 0	0.665 nmol/L STANDARD_DEVIATION 0.16	0.396 nmol/L STANDARD_DEVIATION 0	0.464 nmol/L STANDARD_DEVIATION 0.255	—	0.512 nmol/L STANDARD_DEVIATION 0.484	—	0.418 nmol/L STANDARD_DEVIATION 0.257	—	0.500 nmol/L STANDARD_DEVIATION 0.327	—	0.428 nmol/L STANDARD_DEVIATION 0.134
Peak stimulated C-peptide	2.08 nmol/L STANDARD_DEVIATION 1.54	0.28 nmol/L	0.76 nmol/L STANDARD_DEVIATION 0.25	1.10 nmol/L STANDARD_DEVIATION 0.11	0.71 nmol/L STANDARD_DEVIATION 0.26	—	0.81 nmol/L STANDARD_DEVIATION 0.09	—	0.92 nmol/L STANDARD_DEVIATION 0.35	—	1.26 nmol/L STANDARD_DEVIATION 1.12	—	0.97 nmol/L STANDARD_DEVIATION 0.45
Sex: Female, Male Female	20 Participants	1 Participants	3 Participants	1 Participants	4 Participants	0 Participants	3 Participants	0 Participants	1 Participants	1 Participants	2 Participants	2 Participants	2 Participants
Sex: Female, Male Male	25 Participants	0 Participants	2 Participants	1 Participants	6 Participants	2 Participants	2 Participants	2 Participants	4 Participants	1 Participants	3 Participants	0 Participants	2 Participants
Time from diagnosis to treatment	102.2 days STANDARD_DEVIATION 36.1	90.0 days	122.6 days STANDARD_DEVIATION 36.3	70.0 days STANDARD_DEVIATION 15.6	101.0 days STANDARD_DEVIATION 35.9	84.5 days STANDARD_DEVIATION 44.5	126.4 days STANDARD_DEVIATION 19.4	113.0 days STANDARD_DEVIATION 53.7	91.0 days STANDARD_DEVIATION 38.2	45.5 days STANDARD_DEVIATION 20.5	100 days STANDARD_DEVIATION 42.2	146.0 days STANDARD_DEVIATION 4.2	95.0 days STANDARD_DEVIATION 21.3
Total daily insulin use	0.42 IU/kg/d STANDARD_DEVIATION 0.27	0.56 IU/kg/d	0.51 IU/kg/d STANDARD_DEVIATION 0.18	0.30 IU/kg/d STANDARD_DEVIATION 0.37	0.37 IU/kg/d STANDARD_DEVIATION 0.14	—	0.53 IU/kg/d STANDARD_DEVIATION 0.46	—	0.23 IU/kg/d STANDARD_DEVIATION 0.18	—	0.39 IU/kg/d STANDARD_DEVIATION 0.2	—	0.67 IU/kg/d STANDARD_DEVIATION 0.27

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk
deaths Total, all-cause mortality	0 / 2	0 / 5	0 / 2	0 / 5	0 / 2	0 / 4	0 / 2	0 / 5	0 / 10	0 / 2	0 / 5	0 / 1
other Total, other adverse events	1 / 2	3 / 5	1 / 2	2 / 5	1 / 2	2 / 4	1 / 2	2 / 5	5 / 10	2 / 2	2 / 5	1 / 1
serious Total, serious adverse events	0 / 2	0 / 5	0 / 2	0 / 5	0 / 2	0 / 4	0 / 2	0 / 5	0 / 10	0 / 2	0 / 5	0 / 1

Outcome results

Primary

Incidence of Treatment-emergent Adverse Events (TEAE)

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

Time frame: up to 6 months

Arm	Measure	Value (NUMBER)
AG019 Cohort 1 - Low (Single) Dose/Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	1 Events
AG019 Cohort 1 - Low (Repeat) Dose/Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	6 Events
AG019 Cohort 2 - High (Single) Dose/Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	1 Events
AG019 Cohort 2 - High (Repeat) Dose/Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	19 Events
AG019 Cohort 3 - Low (Single) Dose/Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	1 Events
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	28 Events
AG019 Cohort 4 - High (Single) Dose/Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	1 Events
AG019 Cohort 4 - High (Repeat) Dose/Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	19 Events
Combination Cohort 1 - Active AG019/Teplizumab - Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	91 Events
Combination Cohort 1 - AG019-placebo/Teplizumab-placebo - Adults	Incidence of Treatment-emergent Adverse Events (TEAE)	25 Events
Combination Cohort 2 - Active AG019/Teplizumab - Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	22 Events
Combination Cohort 2 - AG019-placebo/Teplizumab-placebo - Adolescents	Incidence of Treatment-emergent Adverse Events (TEAE)	1 Events

Secondary

AG019 in Feces

The presence of L. lactis (live or dead) in feces will be assessed by Q-PCR (quantitative real-time polymerase chain reaction)

Time frame: Up to 8 days after completion of the treatment

Population: This assessment was not required for single dose patients, result not available

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
AG019 Cohort 1 - Low (Single) Dose/Adults	AG019 in Feces	participants with AG019 in feces	3 Participants
AG019 Cohort 1 - Low (Single) Dose/Adults	AG019 in Feces	participants with no AG019 in feces	2 Participants
AG019 Cohort 1 - Low (Repeat) Dose/Adults	AG019 in Feces	participants with AG019 in feces	3 Participants
AG019 Cohort 1 - Low (Repeat) Dose/Adults	AG019 in Feces	participants with no AG019 in feces	1 Participants
AG019 Cohort 2 - High (Single) Dose/Adults	AG019 in Feces	participants with AG019 in feces	9 Participants
AG019 Cohort 2 - High (Single) Dose/Adults	AG019 in Feces	participants with no AG019 in feces	1 Participants
AG019 Cohort 2 - High (Repeat) Dose/Adults	AG019 in Feces	participants with AG019 in feces	0 Participants
AG019 Cohort 2 - High (Repeat) Dose/Adults	AG019 in Feces	participants with no AG019 in feces	2 Participants
AG019 Cohort 3 - Low (Single) Dose/Adolescents	AG019 in Feces	participants with AG019 in feces	3 Participants
AG019 Cohort 3 - Low (Single) Dose/Adolescents	AG019 in Feces	participants with no AG019 in feces	0 Participants
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	AG019 in Feces	participants with AG019 in feces	0 Participants
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	AG019 in Feces	participants with no AG019 in feces	1 Participants

Secondary

AG019 in Systemic Circulation

The presence of live L. lactis bacteria in blood will be assessed by plating

Time frame: Up to 3 months after initiation of the treatment

Population: This assessment was not required for single dose patients, result not available

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
AG019 Cohort 1 - Low (Single) Dose/Adults	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 1 - Low (Repeat) Dose/Adults	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 2 - High (Single) Dose/Adults	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 2 - High (Repeat) Dose/Adults	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 3 - Low (Single) Dose/Adolescents	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 4 - High (Single) Dose/Adolescents	AG019 in Systemic Circulation	0 Participants
AG019 Cohort 4 - High (Repeat) Dose/Adolescents	AG019 in Systemic Circulation	0 Participants

Secondary

C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months

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.

Time frame: up to 12 months

Arm	Measure	Value (MEAN)	Dispersion
AG019 Cohort 1 - Low (Single) Dose/Adults	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.89 nmol/L	Standard Deviation 0.61
AG019 Cohort 1 - Low (Repeat) Dose/Adults	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.57 nmol/L	Standard Deviation 0.13
AG019 Cohort 2 - High (Single) Dose/Adults	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.48 nmol/L	Standard Deviation 0.19
AG019 Cohort 2 - High (Repeat) Dose/Adults	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.73 nmol/L	Standard Deviation 0.01
AG019 Cohort 3 - Low (Single) Dose/Adolescents	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.57 nmol/L	Standard Deviation 0.21
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.25 nmol/L	Standard Deviation 0
AG019 Cohort 4 - High (Single) Dose/Adolescents	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.62 nmol/L	Standard Deviation 0.48
AG019 Cohort 4 - High (Repeat) Dose/Adolescents	C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months	0.78 nmol/L	Standard Deviation 0.35

Secondary

L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation

The presence of L. lactis-secreted hPINS or hIL-10 in the blood will be assessed by ELISA (enzyme-linked immunosorbent assay)

Time frame: Up to 3 months after initiation of the treatment

Population: Indication for exposure of AG019 secreted hPINS or hIL-10 protein in plasma This assessment was not required for single dose patients, result not available

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
AG019 Cohort 1 - Low (Single) Dose/Adults	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 1 - Low (Repeat) Dose/Adults	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 2 - High (Single) Dose/Adults	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 2 - High (Repeat) Dose/Adults	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 3 - Low (Single) Dose/Adolescents	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 4 - High (Single) Dose/Adolescents	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants
AG019 Cohort 4 - High (Repeat) Dose/Adolescents	L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation	0 Participants

Other Pre-specified

Incidence of Treatment Emergent Adverse Events up to 12 Months

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.

Time frame: Up to 12 months from screening

Arm	Measure	Value (NUMBER)
AG019 Cohort 1 - Low (Single) Dose/Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	1 events
AG019 Cohort 1 - Low (Repeat) Dose/Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	8 events
AG019 Cohort 2 - High (Single) Dose/Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	1 events
AG019 Cohort 2 - High (Repeat) Dose/Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	26 events
AG019 Cohort 3 - Low (Single) Dose/Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	1 events
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	33 events
AG019 Cohort 4 - High (Single) Dose/Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	1 events
AG019 Cohort 4 - High (Repeat) Dose/Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	26 events
Combination Cohort 1 - Active AG019/Teplizumab - Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	97 events
Combination Cohort 1 - AG019-placebo/Teplizumab-placebo - Adults	Incidence of Treatment Emergent Adverse Events up to 12 Months	26 events
Combination Cohort 2 - Active AG019/Teplizumab - Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	23 events
Combination Cohort 2 - AG019-placebo/Teplizumab-placebo - Adolescents	Incidence of Treatment Emergent Adverse Events up to 12 Months	2 events

Source: ClinicalTrials.gov · Data processed: Feb 10, 2026

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)

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Incidence of Treatment-emergent Adverse Events (TEAE)

AG019 in Feces

AG019 in Systemic Circulation

C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 2 Hour Mixed Meal Tolerance Test (MMTT) at 12 Months

L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation

Incidence of Treatment Emergent Adverse Events up to 12 Months