Early Markers of Disease and Response to Therapy
Overview
- Phase
- Early Phase 1
- Intervention
- Abatacept
- Conditions
- Type 1 Diabetes
- Sponsor
- Sandra Lord, MD
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Change in islet-specific exhausted CD8 T cells (%)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to identify early immune markers associated with response to treatment with abatacept in individuals with Type 1 diabetes (T1D). In this open label mechanistic study, participants who were recently diagnosed with T1D (males or females, ages 6-45 and <7months from T1D diagnosis) will be treated with a short-course of abatacept (weekly subcutaneous injections for 3 months). Participants will undergo baseline and repeated mixed meal tolerance testing (MMTT) to assess disease progression and blood samples will be obtained at frequent intervals to measure changes in immune markers.
Investigators
Sandra Lord, MD
Clinical Director, Center for Interventional Immunology
Benaroya Research Institute
Eligibility Criteria
Inclusion Criteria
- •≤ 7 months from type 1 diabetes diagnosis based on ADA criteria
- •\> 21 days from type 1 diabetes diagnosis or metabolically stable per study physician assessment
- •Males and females 6-55 years of age, inclusive, at time of screening visit
- •Peak MMTT stimulated C-peptide ≥ 0.2 pmol/ml
- •Females of child-bearing age must be willing to use effective birth control for 1 year (which may include abstinence) from screening visit and undergo regular pregnancy testing
- •Up to date for clinically recommended immunizations prior to screening
- •Willing to forgo live vaccines 3 months prior to the screening visit until three months following last study drug administration
- •Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is \< 18 years of age
- •Weight ≥ 20 kg at baseline visit
- •HbA1c ≤ 8.5% at baseline visit
Exclusion Criteria
- •Concurrent or recent (within the past 30 days of screening MMTT (visit -1)) use of non-insulin therapies aimed to control hyperglycemia
- •Females who are pregnant or lactating
- •Immunodeficiency or clinically significant chronic lymphopenia
- •Have an active infection at time of screening or baseline visit
- •Recent exposure, or possible or known active SARS-CoV-2 infection as defined by public health guidelines
- •Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection
- •Active infection with EBV or CMV, defined by real-time PCR
- •History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac disease and stable thyroid disease
- •Require use of other immunosuppressive agents for any other condition
- •Use of medications known to influence glucose tolerance
Arms & Interventions
Abatacept
Abatacept will be given by a subcutaneous (SC) formulation weekly for three months.
Intervention: Abatacept
Outcomes
Primary Outcomes
Change in islet-specific exhausted CD8 T cells (%)
Time Frame: 0 to 2 weeks
% of CD8+ T cells (CD8+PD-1+KLRG1+CD57-)
Change in insulin antibody titers (NIDDK units/mL)
Time Frame: 0 to 2 weeks
Insulin antibody titers
Change in B-cell transcriptional module (CD19.mod) (composite score)
Time Frame: 0 to 2 weeks
CD19 mod is composite score of B cell transcripts.
Change in frequency of B cells within total PBMC (%)
Time Frame: 0 to 2 weeks
% of B cells
Change in inflammatory Index by serum transcriptional exposure assay (composite score)
Time Frame: 0 to 2 weeks
Inflammatory Index (359). This is an inflammatory index based on transcription of 359 probe sets (I.I.359) calculated by dividing the average signal intensity of the 103 probe sets generally annotated as 'inflammatory' by the average signal intensity of the 256 probe sets generally annotated as 'regulatory'
Change in EOMES CD8 whole blood gene expression signature (composite score)
Time Frame: 0 to 2 weeks
Gene transcript score for EOMES module
Change in frequency of TfH within total CD4 T cells (%)
Time Frame: 0 to 2 weeks
% of TfH cells within CD4+ T cells