Allogeneic Regulatory Dendritic Cell (DCreg) Renal Study

NCT03726307 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY19040393U01AI136779
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and feasibility of treatment involving a single infusion of donor-derived regulatory dendritic cells (DCreg) in first time, living donor renal transplant recipients. DCreg will be prepared from monocytes obtained by leukapheresis from prospective (non-mobilized) living kidney donors and infused into the respective recipients 7 days before renal transplantation. This study will enroll 28 subjects (14 recipients, 14 donors). The duration of follow-up will be:

• 1 week following the leukapheresis procedure for donors and
• 2 years following their DCreg infusion for kidney recipients.

Conditions

Kidney Transplant; Renal Transplant Recipients

Keywords

donor recipient pairs; allogeneic regulatory dendritic cell therapy (DCreg); DCreg therapy; de novo (first) live-donor renal transplant recipients

Outcome Measures

Primary Outcomes (1)

• Composite Outcome: Proportion of Participants who Experience any of the Pre-Specified Safety Events

  Safety will be assessed by summarizing the proportion of participants who experience any of the following events from the initiation of the regulatory dendritic cells (DCreg) infusion administered 7 days prior to kidney transplant to 1 year post-transplant: * Recipient death attributed to receipt of DCreg, * NCI-CTCAE Grade 4 or higher DCreg infusion reaction, * NCI-CTCAE Grade 4 or higher infection, * Malignancy other than non-melanoma skin cancer, * Pre-transplant Donor Specific Antibodies (DSA), * Post-transplant DSA, * Biopsy-proven acute rejection (BPAR) by BANFF 2017 criteria (grade ≥2A), or * Non-surgical graft loss. * Reference: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).

  Seven Days Prior to Transplant Surgery(e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant

Secondary Outcomes (8)

• Incidence of Death Attributed to Participant Receipt of Regulatory Dendritic Cells (DCreg)

  Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant

• Incidence of Adverse Event: CTCAE Grade 4 or Higher Infusion Reaction

  Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant

• Incidence of Adverse Event:CTCAE Grade 4 or Higher Infection

  Seven Days Prior to Transplant Surgery (e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant

• Incidence of Adverse Event: Malignancy

  Seven Days Prior to Transplant Surgery(e.g. Day of Regulatory Dendritic Cells (DCreg) Infusion) up to 1-Year Post-Transplant

• Incidence of Pre-Transplant Donor Specific Antibodies (DSA)

  Baseline (Seven Days Prior to Transplant Surgery, "Pre" -Regulatory Dendritic Cells (DCreg)) Infusion) up to within 48 Hours of Transplant

Study Arms (3)

DCreg: 0.5 million cells/kg+SOC

EXPERIMENTAL

N=3 participants will receive 0.5 (± 0.1) million cells/kg body weight as a single infusion. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Biological: DCreg: 0.5 million cells/kg+SOC

DCreg: 1.2 million cells/kg+SOC

EXPERIMENTAL

N=3 participants will receive 1.2 (± 0.2) million cells/kg body weight as a single infusion. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Biological: DCreg: 1.2 million cells/kg+SOC

DCreg:2.5 to 5.0 million cells/kg+SOC

EXPERIMENTAL

N=8 participants will receive 25 to 5.0 million cells /kg body weight as a single infusion. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Biological: DCreg:2.5 to 5.0 million cells/kg+SOC

Interventions

DCreg: 0.5 million cells/kg+SOC BIOLOGICAL

DCreg 0.5 (±0.1) million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Also known as: Regulatory Donor-Derived Dendritic Cells (DCreg)

DCreg: 0.5 million cells/kg+SOC

DCreg: 1.2 million cells/kg+SOC BIOLOGICAL

DCreg 1.2 (±02) million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Also known as: Regulatory Donor-Derived Dendritic Cells (DCreg)

DCreg: 1.2 million cells/kg+SOC

DCreg:2.5 to 5.0 million cells/kg+SOC BIOLOGICAL

DCreg 2.5 to 5.0 million cells/kilogram body weight infused as a single dose. Standard of Care (SOC) immunosuppressive agents (ISA): Participants will receive combination ISA according to the site's SOC regimen, with two exceptions: * mycophenolic acid (MPA) will be initiated 7 days before transplant, at the time of donor DCreg infusion, instead of on the day of transplant; and * the pre-transplant dose of MPA will be half the standard post-transplant dose due to increased drug bioavailability in recipients with low glomerular filtration rate (GFR). Participants will be maintained on triple IS therapy with MPA, tacrolimus, and prednisone after transplant, a combination regimen widely applied as SOC at many transplant centers in North America and worldwide.

Also known as: Regulatory Donor-Derived Dendritic Cells (DCreg)

DCreg:2.5 to 5.0 million cells/kg+SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Donor Eligibility Criteria:
• Able to understand and provide informed consent;
• Male or female \>/= 18 years of age
• Meets all standard institutional criteria for kidney donation and Health Agency criteria for kidney donation;
• For females of childbearing potential, a negative urine or serum pregnancy test;
• Negative for Human Immunodeficiency Virus type 1 (HIV) -1 (antigen and Nucleic Acid Testing (NAT)), HIV-2, Human T-cell leukemia virus type 1 (HTLV-1), and HTLV-2;
• Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and core antibody), and Treponema pallidum infection;
• Negative for West Nile Virus;
• Negative health history for Creutzfeldt-Jakob disease;
• No live vaccines within 8 weeks prior to leukapheresis;
• No medical condition(s) that the investigator deems incompatible with participation in the trial; and
• No use of investigational drugs within 12 weeks of participation.
• Must be able to understand and provide informed consent;
• Is \>/= 18 years old at the time of informed consent;
• Is undergoing a living donor renal transplant;

You may not qualify if:

• Panel Reactive Antibody (PRA \>20%);
• Positive T or B Cell Flow Crossmatch prior to transplant;
• Presence of donor specific antibody (DSA) ≥ to mean fluorescence intensity (MFI) of 1000, or DSA between 500 and 1000, if a specific shared epitope pattern is present;
• Recipient of multi-organ transplant;
• Any prior renal or extra-renal transplant with HLA class II antigen mismatch shared with prior organ;
• Epstein-Barr Virus (EBV) Immunoglobulin G (IgG) negative if the donor is EBV positive;
• Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (HCV) antibody (if hepatitis C antibody positive, confirm negative infection by HCV RNA), or positivity for hepatitis B surface antigen;
• History of malignancy witin the past 5 years unless standard institutional criteria detailed in Appendix 6 have been met;
• High risk for recurrence of renal disease: Hemolytic Uremic Syndrome Thrombotic Thrombocytopenic Purpura (HUS-TTP); Focal Segmental Glomerular Sclerosis (FSGS); or Aggressive native kidney disease.
• Compensated and decompensated cirrhosis of liver and/or portal hypertension;
• Chronic Obstructive Pulmonary Disease requiring nasal oxygen, and/or pulmonary hypertension (mean pulmonary pressure \>45mm/hg);
• Any history of stroke with neurological deficit;
• Any condition that, in the opinion of the investigator, confers excessive risk for participation in this phase 1 study;
• Presence of a condition that requires treatment with an immunosuppressive agent, other than a physiologic dose of corticosteroid;
• Live vaccines within 8 weeks prior to transplant;

Sponsors & Collaborators

• Angus W. Thomson PhD DSc: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Pittsburgh, Starzl Transplantation Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.

  PMID: 24472190 BACKGROUND

• Haas M. The Revised (2013) Banff Classification for Antibody-Mediated Rejection of Renal Allografts: Update, Difficulties, and Future Considerations. Am J Transplant. 2016 May;16(5):1352-7. doi: 10.1111/ajt.13661. Epub 2016 Feb 4.

  PMID: 26696524 BACKGROUND

Related Links

• NIH NCI Common Terminology Criteria for Adverse Events (CTCAE)

Study Officials

• Amit D. Tevar, MD, FACS

  University of Pittsburgh: Starzl Transplantation Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Open-label, dose-escalation, phase 1 clinical trial.

Study Record Dates

• First Submitted: October 29, 2018
• First Posted: October 31, 2018
• Study Start: April 10, 2019
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)