Abatacept Conversion in Kidney Transplantation

Emory University

Status and phase: Active, not recruiting; Phase 2

Conditions: Renal Transplant Recipient

Treatments: Drug: Abatacept; Drug: Belatacept

Study type: Interventional

Funder types: Other

Identifiers

NCT04955366

STUDY00001855

Details and patient eligibility

About

This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function.The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.

Full description

This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function. Research subjects will be recruited from those who were initiated on belatacept at the time of their kidney transplant and have been stable on belatacept therapy for at least 2 years post-transplant and off CNI therapy for at least 6 months.

A total of 86 subjects will be randomized in equal numbers, 43 patients in each arm. Enrollment of all 86 patients is expected to be completed within 1.5 years. All patients will be actively followed in the study for 24 months following randomization. The patient participation is projected to last a total of 3.5 years with data analysis to follow.

The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. Adult (age ≥18 years currently)

2. First-time renal transplant recipients of either living donor or deceased donor

   1. Treatment with belatacept from the time of transplant
   2. At least 2 years post-transplant and off CNI therapy for at least 6 months

3. Patients at low immunologic risk

   1. First time transplant
   2. HLA antibody screen with PRA < 80% against class I and class II antigens
   3. Negative crossmatch (actual or virtual)
   4. No donor specific anti-HLA antibody (DSA)
   5. No more than one episode of rejection (Banff grade 1A or greater)
   6. No episodes of rejection (borderline or greater) within the last 6 months prior to study participation
   7. No rejection of Banff grade IIB or greater

4. Immunosuppression consisting of belatacept (5mg/kg q 1M), mycophenolate mofetil (at least 1000 mg daily), or equivalent mycophenolic acid (720 mg daily) or azathioprine (1- 2 mg/kg daily) dose, and prednisone 5 mg daily.

5. Confirmed Tb screening at the time of transplantation

Exclusion criteria

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

1. Repeat renal transplant, or multi-organ transplant recipient
2. History of more than one episode of biopsy-proven acute rejection (Banff grade 1A or greater), or of any episode of rejection of Banff 97 grade IIB or greater, or any rejection (borderline or greater) within the last 6 months
3. Pregnancy (women of childbearing potential must use adequate contraception during study)
4. GFR less than 35
5. Serum creatinine at enrollment more than 30% higher than at 3 months (±4 weeks) prior to randomization
6. Recent history of clinically significant proteinuria (urinary protein/Cr ratio >1.0)
7. Receiving belatacept at a dose other than 5 mg/kg body weight
8. Receiving mycophenolate mofetil at a dose of less than 1000 mg po QD (or mycophenolic acid or azathioprine equivalent).
9. Receiving prednisone at a dose greater than 5 mg po qd within 3 months of enrollment
10. Not currently receiving maintenance immunosuppression with prednisone
11. Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization
12. Evidence of CMV viremia or clinical CMV infection within the last 3 months prior to randomization.
13. BK viremia of greater than 4.3 DNA log copies/mL (greater than 20,000 copies/mL) within 3 months of randomization
14. Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required)
15. Known HIV-positivity (testing not required)
16. Presence of donor specific antibody by Luminex single antigen bead assay, or antibody screen (% PRA) above 80%.
17. History of substance abuse or psychiatric disorder not compatible with study adherence and follow up.
18. History of medical noncompliance
19. Untreated latent Tb (as determined from prior Tb screening at the time of transplantation)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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87 participants in 2 patient groups

Belatacept group (Control Group)

Active Comparator group

Description:

Participants will receive the following: * Belatacept: 5 mg/kg i.v. monthly * Blood draws for PD studies at baseline/Month 0 and Month 6 fora total of two timepoints. * HLA labs at 6, 12 and 24 months * Basic chemistry panel (CP Basic) every 3 months per clinical protocol for efficacy analysis * Hemoglobin A1c at Screening visit * Urine pregnancy test via test kit for WOCP at Screening visit * BK and CMV testing at 6, 12, and 24 months

Treatment:

Drug: Belatacept

Abatacept Group (Conversion Group)

Experimental group

Description:

Participants will receive the following: * Abatacept 125 mg s.c. weekly * Safety labs every 2 weeks (months 0-3) then monthly (months 4-12) * Blood draws forPK atMonth 6, Month 12, and two random time points in between Month 6 and Month 12 for a total of four time points. * Blood draws for PD studies at baseline/Month0 and Month 6 fora total of two timepoints. * HLA labs at 6, 12 and 24 months * Basic chemistry panel (CP Basic) at each study visit per clinical protocol for efficacy analysis * Hemoglobin A1c at Screening visit * Urine pregnancy test via test kit for WOCP at screening * BK and CMV testing at 6, 12, and 24 months

Treatment:

Drug: Abatacept