Early Markers of Disease and Response to Therapy

Type 1 Diabetes Clinical Trial

Official title:

Early Markers of Disease and Response to Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04118153
• Other study ID #: DREAMT V1.0
• Status: Completed
• Phase: Early Phase 1
• Start date: March 5, 2021
• Est. completion date: May 24, 2024

Study information

• Verified date: May 2024
• Source: Benaroya Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 24, 2024
• Est. primary completion date: May 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Abatacept
Abatacept will be administered by subcutaneous injections weekly for 3 months. Dosing is according to body weight at screening visit and will be administered as follows: up to 25 kg receive 50 mg (0.4 mL); 25 to <50 kg receive 87.5 mg (0.7 mL), and > 50 kg receive 125 mg (1.0 mL) per dose.

Locations

Country	Name	City	State
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Benaroya Research Institute	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Sandra Lord, MD	Juvenile Diabetes Research Foundation, Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in insulin antibody titers (NIDDK units/mL)	Insulin antibody titers	0 to 2 weeks
Primary	Change in frequency of B cells within total PBMC (%)	% of B cells	0 to 2 weeks
Primary	Change in inflammatory Index by serum transcriptional exposure assay (composite score)	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'	0 to 2 weeks
Primary	Change in B-cell transcriptional module (CD19.mod) (composite score)	CD19 mod is composite score of B cell transcripts.	0 to 2 weeks
Primary	Change in islet-specific exhausted CD8 T cells (%)	% of CD8+ T cells (CD8+PD-1+KLRG1+CD57-)	0 to 2 weeks
Primary	Change in EOMES CD8 whole blood gene expression signature (composite score)	Gene transcript score for EOMES module	0 to 2 weeks
Primary	Change in frequency of TfH within total CD4 T cells (%)	% of TfH cells within CD4+ T cells	0 to 2 weeks