A Study to Assess the Safety and Tolerability of Differen... | NCT03751007 | Trialant
NCT03751007
Sponsor
Precigen Actobio T1D, LLC
Status
Completed
Last Update Posted
Feb 1, 2023Actual
Enrollment
45Actual
Phase
Phase 1Phase 2
Conditions
Diabetes type1
Interventions
AG019 - Low Dose
Teplizumab
Placebo-AG019
Placebo-Teplizumab
AG019 - High Dose
AG019 - High Dose
Countries
United States
Belgium
Protocol Section
Identification Module
NCT ID
NCT03751007
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AG019-T1D-101
Secondary IDs
ID
Type
Description
Link
2017-002871-24
EudraCT Number
Brief 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)
Official Title
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)
Acronym
Not provided
Organization
Precigen Actobio T1D, LLCINDUSTRY
Status Module
Record Verification Date
Jan 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 24, 2018Actual
Primary Completion Date
Oct 13, 2021Actual
Completion Date
Oct 13, 2021Actual
First Submitted Date
Nov 8, 2018
First Submission Date that Met QC Criteria
Nov 20, 2018
First Posted Date
Nov 23, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Oct 13, 2022
Results First Submitted that Met QC Criteria
Jan 31, 2023
Results First Posted Date
Feb 1, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 31, 2023
Last Update Posted Date
Feb 1, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Precigen Actobio T1D, LLCINDUSTRY
Collaborators
Name
Class
Intrexon Actobiotics NV, d/b/a Precigen Actobio
UNKNOWN
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
Conditions Module
Conditions
Diabetes type1
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
45Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
AG019 Cohort 1 - Low Dose/Adults
Experimental
Biological: AG019 - Low Dose
AG019 Cohort 2 - High Dose/Adults
Experimental
Biological: AG019 - High Dose
AG019 Cohort 3 - Low Dose/Adolescents
Experimental
Biological: AG019 - Low Dose
AG019 Cohort 4 - High Dose/Adolescents
Experimental
Biological: AG019 - High Dose
Combination Cohort 1 - Adults
Experimental
Drug: Teplizumab
Drug: Placebo-AG019
Drug: Placebo-Teplizumab
Biological: AG019 - High Dose
Combination Cohort 2 - Adolescents
Experimental
Drug: Teplizumab
Drug: Placebo-AG019
Drug: Placebo-Teplizumab
Biological: AG019 - High Dose
Interventions
Name
Type
Description
Arm Group Labels
Other Names
AG019 - Low Dose
Biological
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)
AG019 Cohort 1 - Low Dose/Adults
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
up to 6 months
Secondary Outcomes
Measure
Description
Time Frame
AG019 in Systemic Circulation
The presence of live L. lactis bacteria in blood will be assessed by plating
Up to 3 months after initiation of the treatment
L. Lactis-secreted hPINS or hIL-10 in Systemic Circulation
Other Outcomes
Measure
Description
Time Frame
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.
Up to 12 months from screening
Eligibility Module
Eligibility 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 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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
12 Years
Maximum Age
40 Years
Standard Ages
ChildAdult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Chantal Mathieu, MD
University Hospital of Leuven, Clinical and Experimental Endocrinology
Principal Investigator
Kevan Herold, MD
Yale Center for Clinical Investigation; Yale University
Mathieu C, Wiedeman A, Cerosaletti K, Long SA, Serti E, Cooney L, Vermeiren J, Caluwaerts S, Van Huynegem K, Steidler L, Blomme S, Rottiers P, Nepom GT, Herold KC; AG019-T1D-101 Trial Investigators. 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. Diabetologia. 2024 Jan;67(1):27-41. doi: 10.1007/s00125-023-06014-2. Epub 2023 Oct 2.
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
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
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
AG019 Cohort 1 - Low (Single) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
FG001
AG019 Cohort 1 - Low (Repeat) Dose/Adults
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jun 11, 2020
Oct 13, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
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.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Quadruple
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.
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).
Combination Cohort 1 - Adults
Combination Cohort 2 - Adolescents
Placebo-AG019
Drug
Formulated identically to AG019 with the active ingredient removed.
Combination Cohort 1 - Adults
Combination Cohort 2 - Adolescents
Placebo-Teplizumab
Drug
Formulated identically to teplizumab with the active ingredient removed.
Combination Cohort 1 - Adults
Combination Cohort 2 - Adolescents
AG019 - High Dose
Biological
Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks
AG019 Cohort 2 - High Dose/Adults
AG019 Cohort 4 - High Dose/Adolescents
AG019 - High Dose
Biological
Solid, orally administered capsule - 6 capsules per day for 8 weeks.
Combination Cohort 1 - Adults
Combination Cohort 2 - Adolescents
The presence of L. lactis-secreted hPINS or hIL-10 in the blood will be assessed by ELISA (enzyme-linked immunosorbent assay)
Up to 3 months after initiation of the treatment
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)
Up to 8 days after completion of the treatment
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.
up to 12 months
San Francisco
California
94158
United States
Coastal Metabolic Research Centre
Ventura
California
93003
United States
University of Colorado
Aurora
Colorado
80045
United States
Yale Center for Clinical Investigation
New Haven
Connecticut
06519
United States
University of Miami
Miami
Florida
33136
United States
University of South Florida
Tampa
Florida
33612
United States
Barry J Reiner, MD, LLC
Baltimore
Maryland
21229
United States
University of Minnesota Health
Minneapolis
Minnesota
55454
United States
University of Missouri-Kansas City School of Medicine
Kansas City
Missouri
64108
United States
Sanford Children's Specialty Clinic
Sioux Falls
South Dakota
57117
United States
University Diabetes and Endocrine Consultants
Chattanooga
Tennessee
37411
United States
Texas Diabetes & Endocrinology, P.A.
Austin
Texas
78749
United States
Research Institute of Dallas
Dallas
Texas
75231
United States
Benaroya Research Institute
Seattle
Washington
98101
United States
UZ Brussel
Brussels
1090
Belgium
UZ Antwerpen
Edegem
2650
Belgium
UZ Leuven
Leuven
3000
Belgium
Derived
Alexander LM, van Pijkeren JP. Modes of therapeutic delivery in synthetic microbiology. Trends Microbiol. 2023 Feb;31(2):197-211. doi: 10.1016/j.tim.2022.09.003. Epub 2022 Oct 8.
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
FG002
AG019 Cohort 2 - High (Single) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
FG003
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
FG004
AG019 Cohort 3 - Low (Single) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
FG005
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
FG006
AG019 Cohort 4 - High (Single) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
FG007
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
FG008
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.
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
FG010
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.
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
FG0002 subjects
FG0015 subjects
FG0022 subjects
FG0035 subjects
FG0042 subjects
FG0054 subjects
FG0062 subjects
FG0075 subjects
FG00810 subjects
FG0092 subjects
FG0105 subjects
FG0111 subjects
COMPLETED
FG0002 subjects
FG0015 subjects
FG0022 subjects
FG0034 subjects
FG0042 subjects
FG0054 subjects
FG0062 subjects
FG0074 subjects
FG00810 subjects
FG0092 subjects
FG0104 subjects
FG0110 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
FG0101 subjects
FG0111 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
AG019 Cohort 1 - Low (Single) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
BG001
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
BG002
AG019 Cohort 2 - High (Single) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
BG003
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
BG004
AG019 Cohort 3 - Low (Single) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
BG005
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
BG006
AG019 Cohort 4 - High (Single) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
BG007
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
BG008
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
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
BG010
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
IDAA1c values below or equal to 9 generally represent partial disease remission.
this assessment was not required for single dose patients, result not available
Mean
Standard Deviation
units on a scale'
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0015
ParticipantsBG002
Fasting C-peptide
this assessment was not required for single dose patients, result not available
Mean
Standard Deviation
nmol/L
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0015
ParticipantsBG002
Peak stimulated C-peptide
this assessment was not required for single dose patients, result not available
Mean
Standard Deviation
nmol/L
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0015
ParticipantsBG002
Mean 2H C-peptide AUC
Mixed Meal Tolerance test (MMTT)-stimulated 2-hour C-peptide area under the curve (AUC) was defined as the mean area under the C-peptide level time curve over the 2-hour period divided by the duration after an MMTT.
Mean 2h AUC is the AUC (expressed as nmol*min/L) divided by the number of minutes (120 min).
this assessment was not required for single dose patients, result not available
Mean
Standard Deviation
nmol/L
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0015
Total daily insulin use
this assessment was not required for single dose patients, result not available
Mean
Standard Deviation
IU/kg/d
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0015
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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
Posted
Number
Events
up to 6 months
ID
Title
Description
OG000
AG019 Cohort 1 - Low (Single) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
OG001
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG002
AG019 Cohort 2 - High (Single) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
OG003
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG004
AG019 Cohort 3 - Low (Single) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
OG005
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG006
AG019 Cohort 4 - High (Single) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
OG007
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG008
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG010
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
Units
Counts
Participants
OG0002
OG0015
OG0022
OG003
Title
Denominators
Categories
Title
Measurements
OG0001
OG0016
OG0021
OG003
Secondary
AG019 in Systemic Circulation
The presence of live L. lactis bacteria in blood will be assessed by plating
This assessment was not required for single dose patients, result not available
Posted
Count of Participants
Participants
Up to 3 months after initiation of the treatment
ID
Title
Description
OG000
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG001
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG002
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG003
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
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)
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
Posted
Count of Participants
Participants
Up to 3 months after initiation of the treatment
ID
Title
Description
OG000
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG001
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG002
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG003
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
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)
This assessment was not required for single dose patients, result not available
Posted
Count of Participants
Participants
Up to 8 days after completion of the treatment
ID
Title
Description
OG000
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG001
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG002
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 (repeat dose).
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.
Posted
Mean
Standard Deviation
nmol/L
up to 12 months
ID
Title
Description
OG000
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG001
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG002
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 (repeat dose).
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.
Posted
Number
events
Up to 12 months from screening
ID
Title
Description
OG000
AG019 Cohort 1 - Low (Single) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
OG001
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG002
AG019 Cohort 2 - High (Single) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
OG003
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG004
Time Frame
Adverse events were collected from signature of informed consent until completion of the study (or premature withdrawal), an average of 13 months (1 month of screening plus 12 months of study participation).
Description
All adverse events are listed, regardless of treatment emergence, severity, or relationship to AG019 or teplizumab. The results of the primary endpoint (incidence of TEAE up to 6 months) are outlined in the Endpoints section.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
AG019 Cohort 1 - Low (Single) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
0
2
0
2
1
2
EG001
AG019 Cohort 1 - Low (Repeat) Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
0
5
0
5
3
5
EG002
AG019 Cohort 2 - High (Single) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
0
2
0
2
1
2
EG003
AG019 Cohort 2 - High (Repeat) Dose/Adults
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
0
5
0
5
2
5
EG004
AG019 Cohort 3 - Low (Single) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
0
2
0
2
1
2
EG005
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
0
4
0
4
2
4
EG006
AG019 Cohort 4 - High (Single) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
0
2
0
2
1
2
EG007
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
0
5
0
5
2
5
EG008
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
0
2
0
2
2
2
EG010
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
0
1
0
1
1
1
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG0030 affected5 at risk
EG0040 affected2 at risk
EG0050 affected4 at risk
EG0060 affected2 at risk
EG0071 events1 affected5 at risk
EG0080 affected10 at risk
EG0090 affected2 at risk
EG0101 events1 affected5 at risk
EG0110 affected1 at risk
Eosinophilia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Erythropenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Iron deficiency anaemia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Microcytic anaemia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Palpitations
Cardiac disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Motion sickness
Ear and labyrinth disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0011 events1 affected5 at risk
EG0020 affected2 at risk
EG003
Retinopathy
Eye disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Abdominal tenderness
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Chronic gastritis
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Coeliac disease
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0011 events1 affected5 at risk
EG0020 affected2 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Glossitis
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Lip dry
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tongue dry
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Administration site pain
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Catheter site pain
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Catheter site pruritus
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Catheter site related reaction
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Chest pain
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Chills
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Fatigue
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Influenza like illness
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0011 events1 affected5 at risk
EG0020 affected2 at risk
EG003
Infusion site irritation
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Pain
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Cytokine release syndrome
Immune system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Selective IgA immunodeficiency
Immune system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Body tinea
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0011 events1 affected5 at risk
EG0020 affected2 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Hordeolum
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Infectious mononucleosis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Influenza
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Medical device site infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0013 events2 affected5 at risk
EG0020 affected2 at risk
EG003
Otitis externa
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Skin infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0014 events3 affected5 at risk
EG0020 affected2 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Viral infection
Infections and infestations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Joint Injury
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0021 events1 affected2 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tooth fracture
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood glucose decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood potassium increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood urea increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Blood uric acid increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Body Temperature decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0021 events1 affected2 at risk
EG003
C-reactive protein increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Eosinophil count increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Epstein-Barr virus test positive
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
International normalised ratio increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Liver function test abnormal
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Monocyte count decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Platelet count increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Protein total increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Prothrombin time prolonged
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Red blood cell count decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Weight increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0023 events1 affected2 at risk
EG003
Iron deficiency
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Growing pains
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Medial tibial stress syndrome
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Systemic lupus erythematosus
Musculoskeletal and connective tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dizziness postural
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Presyncope
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tension headache
Nervous system disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Attention deficit hyperactivity disorder
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Depression
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Panic attack
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Scrotal irritation
Reproductive system and breast disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Vulvovaginal discomfort
Reproductive system and breast disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Nasal discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Painful respiration
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Tonsillar hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0011 events1 affected5 at risk
EG0020 affected2 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0021 events1 affected2 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Scab
Skin and subcutaneous tissue disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Pallor
Vascular disorders
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
haemoglobin increased
Investigations
MedDRA (21.0)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected5 at risk
EG0020 affected2 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Confidentiality and consulting agreements restrict the dissemination of confidential information, but PIs are not restricted to act as a consultant for other companies.
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG006
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
Units
Counts
Participants
OG0005
OG0015
OG0024
OG0035
OG00410
OG0052
OG0064
OG0071
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG004
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG006
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
Units
Counts
Participants
OG0005
OG0015
OG0024
OG0035
OG00410
OG0052
OG0064
OG0071
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG004
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
Units
Counts
Participants
OG0005
OG0014
OG00210
OG0032
OG0043
OG0051
Title
Denominators
Categories
Title
Measurements
participants with AG019 in feces
OG0003
OG0013
OG0029
OG0030
OG0043
OG0050
participants with no AG019 in feces
OG0002
OG0011
OG0021
OG0032
OG004
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG004
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 (repeat dose).
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG006
AG019 Cohort 1 - Low (Repeat)-Dose/Adults
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG007
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
Units
Counts
Participants
OG0005
OG0015
OG00210
OG0032
OG0045
OG0051
OG0065
OG0074
Title
Denominators
Categories
Title
Measurements
OG0000.89± 0.61
OG0010.57± 0.13
OG0020.48± 0.19
OG0030.73± 0.01
OG0040.57± 0.21
OG0050.25± 0
OG0060.62± 0.48
OG0070.78± 0.35
AG019 Cohort 3 - Low (Single) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 1 day (single dose)
OG005
AG019 Cohort 3 - Low (Repeat) Dose/Adolescents
AG019 - Low Dose: Solid, orally administered capsule - 2 capsules per day for 8 weeks (repeat dose)
OG006
AG019 Cohort 4 - High (Single) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 1 day (single dose)
OG007
AG019 Cohort 4 - High (Repeat) Dose/Adolescents
AG019 - High Dose: Solid, orally administered capsule - 6 capsules per day for 8 weeks (repeat dose)
OG008
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.
Placebo-AG019: Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab: Formulated identically to teplizumab with the active ingredient removed.
OG010
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.