Clinical trial NCT04118153: Early Markers of Disease and Response to Therapy
Official title: Early Markers of Disease and Response to Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
name: Medical College of Wisconsin
First posted: 2019-10-08
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. ≤ 7 months from type 1 diabetes diagnosis based on ADA criteria
2. \> 21 days from type 1 diabetes diagnosis or metabolically stable per study physician assessment
3. Males and females 6-55 years of age, inclusive, at time of screening visit
4. Peak MMTT stimulated C-peptide ≥ 0.2 pmol/ml
5. 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
6. Up to date for clinically recommended immunizations prior to screening
7. Willing to forgo live vaccines 3 months prior to the screening visit until three months following last study drug administration
8. Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is \< 18 years of age
9. Weight ≥ 20 kg at baseline visit
10. HbA1c ≤ 8.5% at baseline visit
11. Positive for at least 1 diabetes autoantibody (excluding mIAA in those who have received ≥ 2 weeks of exogenous insulin therapy)

Exclusion Criteria:

1. Concurrent or recent (within the past 30 days of screening MMTT (visit -1)) use of non-insulin therapies aimed to control hyperglycemia
2. Females who are pregnant or lactating
3. Immunodeficiency or clinically significant chronic lymphopenia
4. Have an active infection at time of screening or baseline visit
5. Recent exposure, or possible or known active SARS-CoV-2 infection as defined by public health guidelines
6. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection
7. Active infection with EBV or CMV, defined by real-time PCR
8. History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac disease and stable thyroid disease
9. Require use of other immunosuppressive agents for any other condition
10. Use of medications known to influence glucose tolerance
11. Have any complicating medical or psychological issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. These include pre-existing cardiac disease, COPD, neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).
12. Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
13. Have a history of malignancies
14. Receipt of live vaccine (MMR, intranasal influenza, varicella, rotatvirus) in 3 months before treatment

Primary outcomes:
measure: Change in insulin antibody titers (NIDDK units/mL)
timeFrame: 0 to 2 weeks
measure: Change in frequency of B cells within total PBMC (%)
timeFrame: 0 to 2 weeks
measure: Change in inflammatory Index by serum transcriptional exposure assay (composite score)
timeFrame: 0 to 2 weeks
measure: Change in B-cell transcriptional module (CD19.mod) (composite score)
timeFrame: 0 to 2 weeks
measure: Change in islet-specific exhausted CD8 T cells (%)
timeFrame: 0 to 2 weeks
measure: Change in EOMES CD8 whole blood gene expression signature (composite score)
timeFrame: 0 to 2 weeks
measure: Change in frequency of TfH within total CD4 T cells (%)
timeFrame: 0 to 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Benaroya Research Institute at Virginia Mason
name: Carla Greenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: