Immunological Tolerance in Patients With Mismatched Kidney Transplants

NCT05806749 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Mismatch-Tolerance
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to determine if administration of the drug belumosudil (KD025) will be safe and improve transplant tolerance in subjects undergoing combined Human Leukocyte Antigen (HLA) single haplotype-matched related or 0-3 antigen (at A, B, C, DR) HLA mismatched unrelated living donor kidney and hematopoietic stem cell transplantation.

Conditions

End Stage Kidney Disease; Immunological Tolerance; Kidney Transplant Failure and Rejection; Chronic Kidney Diseases

Keywords

Immunological Tolerance; Kidney Transplant; Tolerance; End Stage Kidney Disease; End Stage Renal Disease; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Determine impact of treatment regimen on patient and kidney allograft survival

  Measure percentage of patients alive and percentage of patients with a functioning graft at 12 months

  12 months

Secondary Outcomes (3)

• Determine probability of successful withdrawal of immunosuppression

  18 months

• Determine risk of kidney allograft rejection

  36 months

• Determine risk of acute and/or chronic graft vs host disease

  36 months

Study Arms (1)

Immune tolerance in mismatched kidney transplant recipient

EXPERIMENTAL

Our goal is to establish this regimen as a novel, safe and effective approach for induction of transplant tolerance in HLA single haplotype-matched related and HLA mismatched unrelated recipients of combined Hematopoietic Stem Cell Transplant(HSCT)/ Kidney Transplant (KT). Patients will undergo conditioning with rATG and TLI, followed by infusion of hematopoeitic stem cells from the same donor, a triple immunosuppressive regimen, and receive belumosudil following the kidney transplant. Immunosuppression taper will be stopped and/or immunosuppression will be resumed for any of the following conditions: (1) loss of chimerism 2) clinical or pathological evidence of acute rejection and (3) clinical or pathological evidence of graft vs host disease.

Combination Product: Donor CD34+, CD3+. and belumosudil

Interventions

Donor CD34+, CD3+. and belumosudil COMBINATION_PRODUCT

Immediately after living donor kidney transplantation, subjects will begin a conditioning regimen of rATG and total lymphoid irradiation. An infusion of at least 8 X106 donor CD34 cells/kg recipient weight and of at least 10 X106 donor CD3 cells/kg recipient weight will then be given. A triple immunosuppressive regimen of tacrolimus, corticosteroids, and mycophenolate will be utilized. Corticosteroids will be given on a tapering schedule from day 0 through the first four months. Tacrolimus will be given on a tapering schedule from day 1 through month 18. Mycophenolate will be given at a fixed dose from day 11 through month 12. Subjects will receive belumosudil 200 mg by mouth daily from day 28 following the kidney transplant through month 24.

Immune tolerance in mismatched kidney transplant recipient

Eligibility Criteria

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

You may qualify if:

• Age 18 and older
• Receiving an HLA single haplotype-matched related living donor or 0-3 antigen (at A, B, C, DR) HLA mismatched unrelated living donor combined kidney and hematopoietic stem cell transplant (the first six subjects will be HLA single haplotype-matched; the final two subjects may be either HLA single-haplotype-matched or 0-3 antigen (at A, B, C, DR) HLA mismatched)
• Agreement to participate in the study and ability to give informed consent
• Meets institutional criteria for kidney and allogeneic hematopoietic stem cell transplant
• Resides or is willing to stay within 3 hours distance from University of California, Los Angeles Medical Center by ground transportation for the first six months post-kidney transplant
• No known contraindication to administration of rATG or radiation
• If a patient is a female of reproductive potential (i.e. no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) patient must be confirmed not pregnancy by a serum or urine pregnancy test and must agree to practice a reliable form of contraception including hormonal treatments, barrier methods or intrauterine device for duration of the study
• Males of reproductive age must consent to use reliable and effective methods to avoid pregnancy
• Karnofsky Performance Score (KPS) ≥ 70
• Adequate cardiac function defined as left ventricular ejection fracture (LVEF) ≥ 40% by Multi Gated Acquisition (MUGA) scan or echocardiogram
• Adequate pulmonary function defined as FVC and DLCO of ≥ 50% of predicted
• Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal
• Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker
• Negative test for COVID 19 by RT -PCR and/or have received COVID 19 vaccinations. Subjects who have not received their COVID-19 vaccination may be enrolled on the trial based on clinical judgement.

You may not qualify if:

• ABO incompatibility with donor
• Previous solid organ transplant
• Multi-organ transplantation
• Previous treatment with rATG or a known allergy to rabbit proteins
• Previous treatment with belumosudil (KD025)
• History of active malignancy within the past 5 years with the exception of:
• Low risk cancer on active surveillance
• Malignancy treated with curative intent with no known active disease \>2 years before the first dose of study treatment and of low potential risk of recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ, and DCIS)
• Pregnant (confirmed by urine or serum pregnancy test) or lactating
• Leukopenia (with a white blood cell count \< 3,000/µL) or thrombocytopenia (with a platelet count \< 100,000/µL)
• INR and/or PTT ≥ 1.5X upper limits of institutional normal
• Positive HLA DSA
• Active bacterial, fungal, mycobacterial, or viral infection (including active hepatitis B and/or C, or West Nile Virus)

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic; Rejection, Psychology; Renal Insufficiency, Chronic

Interventions

CD3 Complex; belumosudil

Condition Hierarchy (Ancestors)

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; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: April 10, 2023
• Study Start: July 7, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (1)