CAMPath and BELimumab for Transplant Tolerance in Sensitized Kidney Transplant Recipients

NCT03591380 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 2017-1385Protocol Version 8/17/2020A539742SMPH/SURGERY/TRANSPLANT
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine whether kidney transplant recipients who receive belimumab (Benlysta®), combined with the standard of care medications for kidney transplant recipients, is safe and effective in helping prevent new donor specific antibodies (DSA) after transplantation. The presence of DSA increases the risk that the kidney transplant recipient's body will reject the new kidney. The investigators are doing this research because it is estimated that greater than 50% of kidney transplant failures are attributed to antibodies produced in the body, that attack the transplanted organ as a foreign object. DSA produced in the body after a kidney transplant, is thought to occur in 20-50% of patients and is associated with a low likelihood that the organ recipient's body will accept the new kidney. A major unmet need in the kidney transplant area are safe and effective therapies to prevent DSA after transplantation.

Conditions

Kidney Transplantation

Keywords

Donor Specific Antibody; Donors, Living; Allograft Tolerance

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Are DSA Positive as Measured by Mean Fluorescence Intensity Greater Than Zero for DSA

  Use descriptive statistics to describe the rate of de novo DSA development as determined using Luminex, graft survival and function as determined by serum creatinine/eGFR and urine protein, rates of acute cellular and antibody mediated rejection.

  12 months from the time of transplant.

Secondary Outcomes (5)

• Number of Participants With DSA Development, Graft Survival, and Cellular and Antibody Rejection

  12 months from the time of transplant

• Report the Nature, Frequency, and Severity of Serious and Non-serious Adverse Events Greater Than or Equal to Grade 2 Per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.

  Monitored for 12 months from the time of transplant

• Graft Survival and Function by Serum Creatinine

  1, 3, 6, 9, and 12 months from the time of transplant

• Graft Survival and Function by eGFR

  1, 3, 6, 9, and 12 months from the time of transplant

• Graft Survival and Function by Urine Protein

  1, 3, 6, 9, and 12 months from the time of transplant

Study Arms (1)

Experimental: Belimumab

EXPERIMENTAL

Belimumab 10mg/kg will be administered IV at the following intervals: at the time of transplant (Day 0), then post-transplant at 2, 4, 8, 12, 16, and 20 weeks.

Drug: Belimumab

Interventions

Belimumab DRUG

Kidney transplant recipients (n=5) will receive standard of care (SOC) therapy consisting of alemtuzumab and steroid induction with mycophenolic acid and tacrolimus maintenance immunosuppression, plus induction and treatment for 6 months with belimumab.

Also known as: Benlysta

Experimental: Belimumab

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects 18-60 years of age
• Planned to receive a deceased or living donor kidney transplant
• Sensitized patients: Positive sum DSA \<1000, and/or PRA\>0%.
• Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
• Female subjects must be post-menopausal, surgically sterilized, or she and/or sexual partner must be willing to use an acceptable method of birth control with a \<1% failure rate as stated in the product label from time of study consent, during study participation, and for 16 weeks after the last dose of the study agent (i.e., contraceptive subdermal implant of levonorgestrel or etonogestrel, intrauterine device or intrauterine system, combined estrogen and progestogen oral contraceptive, Injectable progestogen, contraceptive vaginal ring, percutaneous contraceptive patches, or abstinence) for the duration of the study. Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation of male sterility can come from the site personnel's: review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner. Note: Mycophenolate mofetil (MMF) affects the metabolism of oral contraceptives and may reduce their effectiveness. As such, women receiving MMF who are using oral contraceptives for birth control should employ an additional method (e.g., barrier method). Mycophenolate can cause fetal harm when administered to a pregnant female. Use of mycophenolate during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations. Mycophenolate affects the metabolism of oral contraceptives and may reduce their effectiveness. As such, women receiving MMF who are using oral contraceptives for birth control should employ an additional method (e.g., barrier method) resulting in two reliable forms of contraception being used simultaneously before starting study treatments, during therapy, and for 6 weeks after stopping therapy; unless abstinence is the chosen method of contraception
• Female patients of childbearing potential must have a negative serum pregnancy test within 48 hours of transplant. Must be willing to use contraceptives from the time of study consent, during study participation, and for 16 weeks after the last dose of study agent. For sexually active men, condoms should be used during, and for at least 90 days after cessation of mycophenolate treatment. No sperm donation should be made during this period of time. For female partners of male subjects, it is recommended to use highly effective contraception during treatment and for 90 days after the last dose of mycophenolate
• No blood donation should be made by the study subjects during mycophenolate treatment and for at least 6 weeks after stopping mycophenolate treatment
• If stricter female or male contraception requirements are specified in the country-specific label for any study related therapies, they must be followed.
• Male subjects must agree to use an acceptable method for contraception for the duration of the study.
• Female patients of childbearing potential must have a negative serum pregnancy test within 48 hours of transplant. Must be willing to use contraceptives from the time of study consent, during study participation, and for 16 weeks after the last dose of study agent. Reproductive Status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below).
• Post-menopause is defined as:
• Women who have had amenorrhea for greater than or equal to 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level \> 35 mIU/mL.
• Women who have irregular menstrual periods and a documented serum FSH level \> 35 mIU/mL.
• Women who are taking hormone replacement therapy (HRT).
• The following women are WOCBP:

You may not qualify if:

• ABO incompatible donor kidney
• Deceased donor \<5 years of age
• KDPI greater than or equal to 85%
• HLA identical or matched kidney
• Transplant other than kidney: has previously received a hematopoietic stem cell/marrow transplant or an organ transplant other than a kidney (with the exception of corneal transplantation)
• T- and/or B-cell positive crossmatch by complement dependent cytotoxicity or flow cytometry against the recipient
• Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).
• Hospitalization for treatment of infection within 60 days of Day 0
• Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0
• Have a history of a primary immunodeficiency
• Uncontrolled infection or any other unstable medical condition that could interfere with the study
• Seropositive for HIV, HCV or HBV, except for hepatitis B surface antibody positive
• Have a significant IgG deficiency (IgG level \< 400 mg/dl) Have an IgA deficiency (IgA level \< 10 mg/dL)
• Prior therapy at any time: has ever received any of the following: a) B-cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti-CD2 \[epratuzumab\], anti-CD52 \[alemtuzumab\], BLyS-receptor fusion protein \[BR3\], TACI fragment, crystallizable (Fc), belimumab), or IV cyclophosphamide
• Live vaccines within 30 days

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• GlaxoSmithKline: collaborator
• American College of Surgeons: collaborator

Study Sites (1)

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

belimumab

Results Point of Contact

• Title: David Foley, MD
• Organization: University of Wisconsin - Madison

foley@surgery.wisc.edu

608-263-2527

Study Officials

• David Foley, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is proposed to be an open-label, single-arm, pilot study to test whether the addition of belimumab, to inhibit the B cell survival factor BLyS at the time of kidney transplantation, to standard or care therapy (alemtuzumab and steroid induction with mycophenolic acid and tacrolimus maintenance immunosuppression) will prevent the prevent the generation of de novo DSA

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: July 19, 2018
• Study Start: May 14, 2019
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: January 9, 2023
• Results First Posted: January 9, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)