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)
- Conditions
- Diabetes type1
- Interventions
- Biological: AG019 - Low DoseDrug: Placebo-AG019Drug: Placebo-TeplizumabBiological: AG019 - High Dose
- Registration Number
- NCT03751007
- Lead Sponsor
- Precigen Actobio T1D, LLC
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination Cohort 1 - Adults Placebo-Teplizumab - Combination Cohort 2 - Adolescents Placebo-AG019 - Combination Cohort 2 - Adolescents Placebo-Teplizumab - AG019 Cohort 3 - Low Dose/Adolescents AG019 - Low Dose - Combination Cohort 1 - Adults AG019 - High Dose - Combination Cohort 2 - Adolescents AG019 - High Dose - AG019 Cohort 1 - Low Dose/Adults AG019 - Low Dose - AG019 Cohort 2 - High Dose/Adults AG019 - High Dose - AG019 Cohort 4 - High Dose/Adolescents AG019 - High Dose - Combination Cohort 1 - Adults Teplizumab - Combination Cohort 1 - Adults Placebo-AG019 - Combination Cohort 2 - Adolescents Teplizumab -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (18)
Sanford Children's Specialty Clinic
🇺🇸Sioux Falls, South Dakota, United States
UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
University of Colorado
🇺🇸Aurora, Colorado, United States
Yale Center for Clinical Investigation
🇺🇸New Haven, Connecticut, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of Minnesota Health
🇺🇸Minneapolis, Minnesota, United States
Benaroya Research Institute
🇺🇸Seattle, Washington, United States
University of Miami
🇺🇸Miami, Florida, United States
Research Institute of Dallas
🇺🇸Dallas, Texas, United States
University Diabetes and Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
University of Missouri-Kansas City School of Medicine
🇺🇸Kansas City, Missouri, United States
UZ Brussel
🇧🇪Brussels, Belgium
Texas Diabetes & Endocrinology, P.A.
🇺🇸Austin, Texas, United States
Coastal Metabolic Research Centre
🇺🇸Ventura, California, United States
University of Alabama, Birmingham
🇺🇸Birmingham, Alabama, United States
Barry J Reiner, MD, LLC
🇺🇸Baltimore, Maryland, United States