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)
NCT ID: NCT03751007
Last Updated: 2023-02-01
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
45 participants
INTERVENTIONAL
2018-10-24
2021-10-13
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
SEQUENTIAL
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.
TREATMENT
QUADRUPLE
Study Groups
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AG019 Cohort 1 - Low Dose/Adults
AG019 - Low Dose
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)
AG019 Cohort 2 - High Dose/Adults
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks
AG019 Cohort 3 - Low Dose/Adolescents
AG019 - Low Dose
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)
AG019 Cohort 4 - High Dose/Adolescents
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks
Combination Cohort 1 - 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).
Placebo-AG019
Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab
Formulated identically to teplizumab with the active ingredient removed.
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 8 weeks.
Combination Cohort 2 - 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).
Placebo-AG019
Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab
Formulated identically to teplizumab with the active ingredient removed.
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 8 weeks.
Interventions
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AG019 - Low Dose
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)
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).
Placebo-AG019
Formulated identically to AG019 with the active ingredient removed.
Placebo-Teplizumab
Formulated identically to teplizumab with the active ingredient removed.
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 1 day (single dose) or 8 weeks
AG019 - High Dose
Solid, orally administered capsule - 6 capsules per day for 8 weeks.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
12 Years
40 Years
ALL
No
Sponsors
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Intrexon Actobiotics NV, d/b/a Precigen Actobio
UNKNOWN
Precigen Actobio T1D, LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Chantal Mathieu, MD
Role: PRINCIPAL_INVESTIGATOR
University Hospital of Leuven, Clinical and Experimental Endocrinology
Kevan Herold, MD
Role: PRINCIPAL_INVESTIGATOR
Yale Center for Clinical Investigation; Yale University
Locations
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University of Alabama, Birmingham
Birmingham, Alabama, United States
University of California, San Francisco
San Francisco, California, United States
Coastal Metabolic Research Centre
Ventura, California, United States
University of Colorado
Aurora, Colorado, United States
Yale Center for Clinical Investigation
New Haven, Connecticut, United States
University of Miami
Miami, Florida, United States
University of South Florida
Tampa, Florida, United States
Barry J Reiner, MD, LLC
Baltimore, Maryland, United States
University of Minnesota Health
Minneapolis, Minnesota, United States
University of Missouri-Kansas City School of Medicine
Kansas City, Missouri, United States
Sanford Children's Specialty Clinic
Sioux Falls, South Dakota, United States
University Diabetes and Endocrine Consultants
Chattanooga, Tennessee, United States
Texas Diabetes & Endocrinology, P.A.
Austin, Texas, United States
Research Institute of Dallas
Dallas, Texas, United States
Benaroya Research Institute
Seattle, Washington, United States
UZ Brussel
Brussels, , Belgium
UZ Antwerpen
Edegem, , Belgium
UZ Leuven
Leuven, , Belgium
Countries
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References
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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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2017-002871-24
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
AG019-T1D-101
Identifier Type: -
Identifier Source: org_study_id
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