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)

Phase 1

• Conditions: Recent-onset Type 1 Diabetes mellitus (T1D); MedDRA version: 21.1Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2017-002871-24-BE
• Lead Sponsor: Intrexon T1D Partners, LLC (IT1D)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-30
• Last Update Posted: 22 November 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

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 ADA recommended criteria
- Evidence of auto-antibodies to at least 1 of the following ß-cell autoantigens: insulin, IA-2, GAD65, ZnT8
- 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
- Body weight = 33kg
- Willing and medically able to postpone live vaccine immunizations for at least 8 weeks after randomization
- Ability and willingness of patients to participate fully in all aspects of this clinical study
- Written informed consent obtained and documented
- Willingness to use a continuous glucose monitoring device and willingness to comply with the protocol defined glucose monitoring
- Total bilirubin =1.0 x upper limit of normal (ULN), Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =1.5 x ULN, =1,000 lymphocytes/µL, =1,000 polymorphonuclear neutrophils (PMN)/µL, =100,000 platelets/µL, Hgb =10 g/dL, Serum Creatinin =1.5 x ULN, eGFR =60 mL/min/1.73m², INR =0.1 above upper limit of normal, Absence of clinically significant age appropriate abnormalities on all other lab values, except for abnormalities directly attributable to T1D
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
- Current use of any systemic antibiotics, except for the following: metronidazole (metronidazole), nalidixic acid (first generation quinolone), trimethoprim, sulfamethoxazole (sulfonamide) and/or a combination of both in a ratio 1/19 (sulfonamides)
- 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)
- Untreated hypothyroidism or active Graves’ disease
- Evidence of any active infection with the exception of superficial skin infections
- Vaccination with live virus or organism within 8 weeks prior to randomization
- 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
- 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
- Inability to swallow size 1 capsules
- Alcohol or illicit drug consumption, which in the opinion of the investigator, may interfere with the patient’s ability to comply with the study procedures
- Active psychiatric problems, which in the opinion of the investigator, may interfere with the patient’s ability to comply with study procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified