A Pilot Study Using Autologous Regulatory T Cell Infusion Zortress (Everolimus) in Renal Transplant Recipients

NCT03284242 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 16-0779-F6ACRAD001AUS210T
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll individuals who have end stage renal disease and who are undergoing a solitary kidney transplant. This study is investigating/evaluating the safety and effectiveness of collecting, expanding and infusing a specific certain type of immune cell known as Regulatory T cells (Treg cells) to renal transplant recipients who are using Zortress (Everolimus) as immunosuppressive therapy. Treg cells, once they have been expanded in the laboratory to help prevent kidney rejection. Treg cells are collected from a participant's blood through a procedure called apheresis. Treg cells are a type of white blood cells that are able to suppress the activity of other immune cells responsible for organ rejection. The investigator plans to enroll 12 participants at the University of Kentucky.

Conditions

End Stage Renal Disease; Kidney Transplant

Keywords

Kidney; Transplant

Outcome Measures

Primary Outcomes (4)

• Changes in Tregs Infusion Toxicities

  Laboratory measurement and observed toxicities immediately and with in 24 hours post infusion of Tregs.

  Immediately following Tregs infusion and again within 24 hours after Tregs infusion

• Changes in Kidney Function

  Creatinine level measurement

  for 2 years from the start of the study

• Changes In Steroid Resistance Rejection Rates

  Laboratory measurement

  1, 6 and 12 months post Tregs infusion

• Infectious Complications

  Laboratory measurement

  for 2 years from the start of the study

Secondary Outcomes (2)

• Treg cell measurements within the allograft

  6 to 12 weeks post transplant

• Circulating T cell subset measurements

  twice a week for 4 weeks then weekly for 3 months

Study Arms (1)

Autologous Treg Infusion

EXPERIMENTAL

This will be a single intravenous (IV) infusion. A participant's own expanded regulatory T cells will be added to Albumin, and administered to them. The amount of the solution will be approximately 300 ml and the infusion will take about 3 to 4 hours.

Drug: Treg

Interventions

Treg DRUG

Collect white blood cells to isolate Treg cells for expansion. Once the blood cells are collected the cells will be cultured in the laboratory and will be expanded. After approximately 3 weeks in culture, the cells will have increased in number and be ready for the autologous Treg cell infusion.

Also known as: regulatory T cells

Autologous Treg Infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fluent in English able to understand and provide informed consent
• End stage renal disease listed for primary solitary kidney transplant
• Willing to participate in the study and comply with study requirements
• Female participants must agree to use 2 different birth control methods

You may not qualify if:

• History of previous organ, tissue or cell transplant
• Known sensitivity to Sirolimus, Everolimus, Tacrolimus or MMF
• Previous chronic use of systemic glucocorticoids or other immunosuppression, or biologic immunomodulators
• Significant or active infection: HIV, Hepatitis B and C
• Active cancer or history of cancer within 3 years of screening
• Participation in other study that involved investigational drug or regimens in the preceding 12 months
• History of delayed or abnormal wound healing
• Delayed graft function
• Chronic illness or prior treatment which, in the opinion of the investigator, precludes study participation
• Pregnant or breastfeeding or refusal to us birth control
• Inability or unwillingness to comply with study protocol or procedures
• Chronic use of anticoagulants
• Blood transfusion 3 months prior to transplant
• History of non-compliance

Sponsors & Collaborators

• Roberto Gedaly: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Related Publications (1)

• Gedaly R, De Stefano F, Turcios L, Hill M, Hidalgo G, Mitov MI, Alstott MC, Butterfield DA, Mitchell HC, Hart J, Al-Attar A, Jennings CD, Marti F. mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation. Transplantation. 2019 Apr;103(4):705-715. doi: 10.1097/TP.0000000000002495.

  PMID: 30451741 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roberto Gedaly, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor/Investigator

Model Details: Single intravenous infusion of autologous, ex vivo, expanded Treg cells in renal transplant recipients who are on Everolimus-based immunosupressive therapy.

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: September 15, 2017
• Study Start: March 15, 2019
• Primary Completion: April 10, 2024
• Study Completion: April 10, 2024
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)