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)

Diabetes type1 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03751007
• Other study ID #: AG019-T1D-101
• Secondary ID: 2017-002871-24
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 24, 2018
• Est. completion date: October 13, 2021

Study information

• Verified date: January 2023
• Source: Precigen Actobio T1D, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 13, 2021
• Est. primary completion date: October 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 40 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes type1

Intervention

Biological:
• AG019 - Low Dose
Solid, orally administered capsule - 2 capsules per day for 1 day (single dose) or 8 weeks (repeat dose)

Drug:
• 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.

Biological:
• 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.

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussels
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven	Leuven
United States	University of Colorado	Aurora	Colorado
United States	Texas Diabetes & Endocrinology, P.A.	Austin	Texas
United States	Barry J Reiner, MD, LLC	Baltimore	Maryland
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee
United States	Research Institute of Dallas	Dallas	Texas
United States	University of Missouri-Kansas City School of Medicine	Kansas City	Missouri
United States	University of Miami	Miami	Florida
United States	University of Minnesota Health	Minneapolis	Minnesota
United States	Yale Center for Clinical Investigation	New Haven	Connecticut
United States	University of California, San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington
United States	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota
United States	University of South Florida	Tampa	Florida
United States	Coastal Metabolic Research Centre	Ventura	California

Sponsors (2)

Lead Sponsor	Collaborator
Precigen Actobio T1D, LLC	Intrexon Actobiotics NV, d/b/a Precigen Actobio

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
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	up to 6 months
Secondary	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
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)	Up to 3 months after initiation of the treatment
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)	Up to 8 days after completion of the treatment
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.	up to 12 months