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)

NCT03751007 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: AG019-T1D-1012017-002871-24
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 18

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).

Conditions

Diabetes type1

Outcome Measures

Primary Outcomes (1)

• 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 (4)

• AG019 in Systemic Circulation

  Up to 3 months after initiation of the treatment

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

  Up to 3 months after initiation of the treatment

• AG019 in Feces

  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

  up to 12 months

Other Outcomes (1)

• Incidence of Treatment Emergent Adverse Events up to 12 Months

  Up to 12 months from screening

Study Arms (6)

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

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; AG019 Cohort 3 - Low Dose/Adolescents

Teplizumab DRUG

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

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Precigen Actobio T1D, LLC: lead
• Intrexon Actobiotics NV, d/b/a Precigen Actobio: collaborator

Study Sites (18)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Coastal Metabolic Research Centre

Ventura, California, 93003, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Barry J Reiner, MD, LLC

Baltimore, Maryland, 21229, United States

Location

University of Minnesota Health

Minneapolis, Minnesota, 55454, United States

Location

University of Missouri-Kansas City School of Medicine

Kansas City, Missouri, 64108, United States

Location

Sanford Children's Specialty Clinic

Sioux Falls, South Dakota, 57117, United States

Location

University Diabetes and Endocrine Consultants

Chattanooga, Tennessee, 37411, United States

Location

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, 78749, United States

Location

Research Institute of Dallas

Dallas, Texas, 75231, United States

Location

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

UZ Brussel

Brussels, 1090, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Related Publications (2)

• 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.

  PMID: 37782353 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.

  PMID: 36220750 DERIVED

MeSH Terms

Interventions

teplizumab

Results Point of Contact

• Title: Sven Blomme
• Organization: Precigen Actobio T1D, LLC

sblomme@actobio.com

+3292771177

Study Officials

• Chantal Mathieu, MD

  University Hospital of Leuven, Clinical and Experimental Endocrinology

  PRINCIPAL INVESTIGATOR

• Kevan Herold, MD

  Yale Center for Clinical Investigation; Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 23, 2018
• Study Start: October 24, 2018
• Primary Completion: October 13, 2021
• Study Completion: October 13, 2021
• Last Updated: February 1, 2023
• Results First Posted: February 1, 2023

Record last verified: 2023-01

Locations

BE (3); US (15)