Abatacept Conversion in Kidney Transplantation

Renal Transplant Recipient Clinical Trial

Official title:

Late Abatacept Conversion in Kidney Transplant Recipients Receiving Belatacept: a Prospective, Randomized Controlled Non-inferiority Trial. IM101-884

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04955366
• Other study ID #: STUDY00001855
• Status: Recruiting
• Phase: Phase 2
• Start date: September 22, 2021
• Est. completion date: October 2024

Study information

• Verified date: September 2023
• Source: Emory University
• Contact: Idelberto R Badell, MD
• Phone: 404-712-6562
• Email: ibadell[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 86
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Renal Transplant Recipient

Intervention

Drug:
• Belatacept
Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg monthly
• Abatacept
Abatacept is an immunosuppressive medication and will be given SQ at a dose of 125 mg s.c. weekly

Locations

Country	Name	City	State
United States	Emory University Hospital (EUH)	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mean estimated GFR (eGFR) between randomization and 12 months post baseline	Difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.	Baseline, 12 months post baseline
Secondary	Change in eGFR between abatacept and belatacept groups at 24 months	The treatment difference in eGFR between abatacept and belatacept groups at 24 months, using a monthly repeated measures model and a pre-specified acceptable difference, or non-inferiority margin of 5 ml/min/1.73m2.	Monthly until 24 months post baseline
Secondary	Number of subjects with biopsy proven acute rejection: Acute Cellular Rejection (ACR)	Incidence and severity of acute cellular rejection (ACR)	12 months post baseline, 24 months post baseline
Secondary	Number of subjects with biopsy proven acute rejection: Antibody Mediated Rejection (AMR)	Incidence and severity of antibody mediated rejection (AMR) analyses	12 months post baseline, 24 months post baseline
Secondary	Number of participants with kidney transplant biopsies post baseline	Number of participants with kidney transplant biopsies post baseline	12 months post baseline, 24 months post baseline
Secondary	Proportion of subjects treated for ACR/AMR due to clinical suspicion	Proportion of subjects treated for ACR/AMR due to clinical suspicion	12 months post baseline, 24 months post baseline
Secondary	Number of subjects with de novo anti-donor human leukocyte antigen (HLA) antibodies	Incidence of de novo anti-donor human leukocyte antigen (HLA) antibodies	12 months post baseline, 24 months post baseline
Secondary	First occurrence of graft loss or death post baseline	First occurrence of graft loss or death at 6, 12 and 24 months post baseline	12 months post baseline, 24 months post baseline
Secondary	Number of deaths at 6, 12 and 24 months post baseline	Incidence of death with graft function at 6, 12 and 24 months post baseline	12 months post baseline, 24 months post baseline
Secondary	Incidence of death-censored graft loss post baseline	Incidence of death-censored graft loss at 12 and 24 months	12 months post baseline, 24 months post baseline
Secondary	Compliance with patient-administered subcutaneous abatacept	Compliance with patient-administered subcutaneous abatacept	12 months post baseline, 24 months post baseline
Secondary	Incidence of adverse events	Incidence of adverse events	12 months post baseline, 24 months post baseline
Secondary	Incidence of serious adverse events	Incidence of serious adverse events	12 months post baseline, 24 months post baseline
Secondary	Incidence of events of special interest	Incidence of events of special interest, including CMV viremia, BKV viremia, and serious infections	12 months post baseline, 24 months post baseline
Secondary	Incidence of any malignancy	Incidence of any malignancy including PTLD	12 months post baseline, 24 months post baseline
Secondary	Incidence of subcutaneous injection site complications	Incidence of subcutaneous injection site complications	12 months post baseline, 24 months post baseline
Secondary	Proportion of subjects who develop de-novo, anti-HLA donor specific antibody	Proportion of subjects who develop de-novo, anti-HLA donor specific antibody	12 months post baseline, 24 months post baseline