Early Markers of Disease and Response to Therapy

NCT04118153 | Completed Early Phase 1 FDA Drug

• 1 other identifier: DREAMT V1.0
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (7)

• Change in insulin antibody titers (NIDDK units/mL)

  Insulin antibody titers

  0 to 2 weeks

• Change in frequency of B cells within total PBMC (%)

  % of B cells

  0 to 2 weeks

• 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

• Change in B-cell transcriptional module (CD19.mod) (composite score)

  CD19 mod is composite score of B cell transcripts.

  0 to 2 weeks

• Change in islet-specific exhausted CD8 T cells (%)

  % of CD8+ T cells (CD8+PD-1+KLRG1+CD57-)

  0 to 2 weeks

• Change in EOMES CD8 whole blood gene expression signature (composite score)

  Gene transcript score for EOMES module

  0 to 2 weeks

• Change in frequency of TfH within total CD4 T cells (%)

  % of TfH cells within CD4+ T cells

  0 to 2 weeks

Study Arms (1)

Abatacept

EXPERIMENTAL

Abatacept will be given by a subcutaneous (SC) formulation weekly for three months.

Drug: Abatacept

Interventions

Abatacept DRUG

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.

Also known as: ORENCIA

Abatacept

Eligibility Criteria

• Age: 6 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≤ 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
• Positive for at least 1 diabetes autoantibody (excluding mIAA in those who have received ≥ 2 weeks of exogenous insulin therapy)

You may not qualify if:

• 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
• 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).
• Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
• Have a history of malignancies
• Receipt of live vaccine (MMR, intranasal influenza, varicella, rotatvirus) in 3 months before treatment

Sponsors & Collaborators

• Sandra Lord, MD: lead
• Juvenile Diabetes Research Foundation: collaborator
• Medical College of Wisconsin: collaborator

Study Sites (2)

Benaroya Research Institute

Seattle, Washington, 98101, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Abatacept

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)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Carla Greenbaum, MD

  Benaroya Research Institute at Virginia Mason

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director, Center for Interventional Immunology

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 8, 2019
• Study Start: March 5, 2021
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: June 4, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)