Immune Effects of Vedolizumab With or Without Anti-TNF Pre-treatment in T1D

NCT05281614 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB22-007
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The underlying hypothesis is that vedolizumab will modify immune cell trafficking in type 1 diabetes, and that this will be enhanced by pre-treatment with etanercept. This study will determine whether there is mechanistic evidence in support of this hypothesis and provide preliminary information about safety, efficacy, and tolerability of vedolizumab with and without pretreatment with etanercept in adults with type 1 diabetes (T1D)

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (3)

• Impact on insulin secretion determined by 2-hour MMTT stimulated AUC C-peptide 10 weeks after first vedolizumab dose and 52 weeks after randomization.

  MMTT-Stimulated 2-Hour C-peptide AUC is 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.

  baseline dose to 10 weeks and baseline dose to 52 weeks

• Adverse events of etanercept treatment as a measure of safety and tolerability

  An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event

  baseline to 52 weeks

• Adverse events of vedolizumab treatment as a measure of safety and tolerability

  An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Results will be reported as a rate of each adverse event

  baseline to 52 weeks

Secondary Outcomes (4)

• Frequency of α4β7+ T cells

  baseline to 52 weeks

• Frequency of myeloid DC1 cells

  baseline to 52 weeks

• Frequency and surface marker phenotype of other immune cells such as antigen specific CD4 and CD8 cells, memory and naive T and B cells

  baseline to 52 weeks

• Change in T1D antibody titers

  baseline to 52 weeks

Study Arms (2)

Arm A

EXPERIMENTAL

Arm A will receive 6 weeks of vedolizumab after 8 weeks of etanercept. Final study visit at 52 weeks.

Drug: Etanercept; Drug: Vedolizumab

Arm B

EXPERIMENTAL

Arm B will receive 6 weeks of vedolizumab only. Final study visit at 52 weeks.

Drug: Vedolizumab

Interventions

Etanercept DRUG

Etanercept is a fully humanized monoclonal antibody that targets TNFα.

Also known as: Enbrel

Arm A

Vedolizumab DRUG

Vedolizumab is a humanized monoclonal antibody that targets α4ß7 integrin.

Also known as: Entyvio

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females 18-45 years of age, inclusive
• Diagnosis of T1D between 21 days and 3 years from screening
• Positive for at least one diabetes-related autoantibody any time since diagnosis, including but not limited to:
• Glutamate decarboxylase (GAD-65)
• mIAA, if obtained within 10 days of the onset of exogenous insulin therapy
• IA-2
• ZnT8 (Zinc transporter 8)
• Random (non-fasting) C-peptide or peak MMTT stimulated C-peptide ≥ 0.2 pmol/mL.
• Females of child-bearing potential must be willing to use effective birth control from the screening visit through 12 weeks post last dose of study medication.
• Up to date for clinically recommended immunizations including COVID-19 and seasonal influenza vaccine at least 3 weeks prior to baseline treatment.
• Willing to forgo live vaccines 6 weeks prior to baseline treatment visit until 6 weeks following last treatment visit.
• HbA1c ≤ 8.5% at screening
• Willing and able to give informed consent for participation

You may not qualify if:

• History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
• History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
• History of immunodeficiency
• Recent (within 3 months) serious bacterial, viral, fungal, or other infections
• Pending or positive SARS-CoV-2 test or symptoms of possible COVID-19 illness at baseline treatment visit.
• Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.
• Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.
• Active infection with EBV as defined by real-time polymerase chain reaction (PCR).
• Active infection with CMV as defined by real-time PCR.
• Clinically significant liver function abnormalities as defined by ALT or AST\> 1.5 x the upper limit of age-determined normal (ULN).
• Any of the following hematologic abnormalities:
• White blood count \<3,000/μL or \>14,000/μL
• Lymphocyte count \<800/μL
• Platelet count \<75,000 /μL
• Hemoglobin \<10.0 g/dL

Sponsors & Collaborators

• Benaroya Research Institute: lead
• University of California, San Diego: collaborator

Study Sites (2)

University of California San Diego

La Jolla, California, 92037, United States

Location

Benaroya Research Institute

Seattle, Washington, 98102, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Etanercept; vedolizumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label study with 2 treatment arms

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: March 16, 2022
• Study Start: September 21, 2022
• Primary Completion: January 10, 2024
• Study Completion: January 10, 2024
• Last Updated: May 24, 2024

Record last verified: 2023-02

Locations

US (2)