Clinical trial NCT05975450: Subcutaneous Abatacept in Renal Transplant Recipients
Official title: Early Substitution of Subcutaneous Abatacept for Belatacept as Costimulation Blockade to Minimize Calcineurin Inhibitors (CNI) Exposure After Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Transplant Recipient
Keywords: Renal Transplant
abatacept
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2023-08-03
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: After a kidney transplant, patients take drugs called anti-rejection drugs (immunosuppressives) to prevent their bodies from rejecting the new kidney. At present it is not possible to have a successful transplant without these drugs. These drugs make it possible for a person who receives the transplant to accept the "foreign" kidney. Most patients who get a transplant need to take anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work.

Researchers are looking to learn whether abatacept is as good as belatacept in preventing rejection, whether there are other benefits or harms associated with abatacept treatment, and possibly allows greater flexibility on patient's travel and time since abatacept is self-administered at home.

This study is being done to answer these questions:

Are weekly abatacept injections under the skin a safe and effective substitute for monthly belatacept intravenous (IV) infusions? and How well does the kidney function after switching from belatacept to abatacept?

Detailed description: This is a Phase I, open-label, prospective, single-arm single-center study to evaluate the feasibility, effectiveness, and safety of a regimen substituting subcutaneous abatacept early post-transplant in place of intravenous belatacept as an immunosuppressant in first-time renal transplant recipients.

There is a single arm in this study; the Investigational (abatacept) group. Participants will be assigned to a treatment regimen between 2 and 5 months after transplantation. The study drug will be administered until month 12 post-transplant; at that point, all participants will be transitioned to a physician-directed immunosuppressive regimen post-study.

Eligibility criteria: Inclusion Criteria:

* Must be able to understand and provide informed consent.
* Male or Female, 18-70 years of age at the time of enrollment (all races and ethnicities)
* Negative crossmatch (virtual or physical) at the time of transplant
* No less than 8 weeks, no more than 20 weeks post-transplant at enrollment
* A first-time renal transplant who has been treated with belatacept from the time of transplant, receiving tacrolimus (target trough 3-5 ng/ml), mycophenolate mofetil (or mycophenolic acid or azathioprine), prednisone (also see exclusion criteria).
* eGFR ≥ 40ml/min/m2 \[using 2021 the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\].
* Prior documented evidence of Epstein-Barr virus (EBV) seropositivity must be available.
* Female study participants of childbearing potential must have a negative pregnancy test before enrollment.
* Agreement to use contraception that is more than 80% effective.
* Vaccines are current as per the Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials.
* Study participants must have a negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved Interferon Gamma Release Assay (IGRA) blood test, such as QuantiFERON®-Gold tuberculosis (TB) or T-SPOT®-TB assay. PPD or IGRA testing must be documented to have been performed within the 52 weeks before enrollment. Patients with latent TB may become eligible after completion of treatment.

Exclusion Criteria:

* Inability or unwillingness of a study participant to give written informed consent or comply with the study protocol.
* Recipient of previous organ transplant of any type.
* Multi-organ transplant.
* Calculated Panel Reactive Antibody (cPRA) \>80 at the time of enrollment.
* History of any episode of biopsy-proven Banff rejection (including borderline rejection or any grade of acute TCMR) before enrollment.
* History of any malignancy including lymphoma within 5 years of enrollment. Study participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled.
* Any past or current issue which in the opinion of the investigator may pose additional risks to the participant in the study, may interfere with the study participant's ability to comply with the study requirements, or may impact the quality or interpretation of the data obtained from the study.
* Human immunodeficiency virus (HIV): individuals known to be HIV positive.
* Hepatitis C virus (HCV): any study participant who receives a kidney from a seropositive or HCV RNA PCR-positive donor is ineligible. Any study participant who was HCV RNA PCR positive at transplant is ineligible. Any study participant with a history of HCV seropositivity or HCV infection who has not met the criteria for sustained spontaneous clearance or sustained viral response to therapy is ineligible.
* Hepatitis B virus (HBV): Individuals with any of the following are NOT eligible:

  * Recipient or donor positive for hepatitis B surface antigen (HBsAg)
  * Recipient or donor positive for antibodies to hepatitis B core antigen (anti-HBc)
  * Recipient or donor is known to have had a positive HBV DNA PCR
* Evidence of CMV viremia or clinical CMV infection at any time after transplant.
* Kidney recipients who were CMV seronegative who received an organ from a CMV seropositive donor.
* BK viremia of greater than 4.3 DNA log copies/ml (greater than 20,000 copies/ml) at any time post-transplant.
* Active uncontrolled infection within 1 month of enrollment.
* Clinically significant proteinuria (urinary protein/Cr ratio \>1.0).
* Receiving belatacept at a dose other than 5 mg/kg body weight.
* Receiving mycophenolate mofetil at a dose of less than 1000 mg daily (or mycophenolic acid or azathioprine equivalent).
* Receiving prednisone at a dose greater than 5 mg daily.
* Presence of donor-specific antibody by Luminex single antigen bead assay.

Primary outcomes:
measure: The proportion of subjects who tolerate subcutaneous injections and are compliant with self-administration
timeFrame: Throughout the study intervention (up to 12 months)
measure: The proportion of participants who remain free of biopsy-proven acute T-cell mediated rejection (aTCMR) or antibody-mediated rejection (ABMR) as defined by Banff criteria at or before 12 months after transplantation.
timeFrame: Throughout the study intervention up to 12 months post transplant
measure: The cumulative incidence of serious adverse events
timeFrame: Throughout the study intervention up to 12 months post transplant
measure: Incidence of serious infection of special interest
timeFrame: Throughout the study intervention up to 12 months post transplant
measure: Incidence of patients with cytomegalovirus (CMV) viremia stratified by the magnitude
timeFrame: Throughout the study intervention up to 12 months post transplant
measure: Incidence of patients with BK viremia stratified by the magnitude
timeFrame: Throughout the study intervention up to 12 months post transplant
measure: Incidence of any malignancy
timeFrame: Throughout the study intervention up to 12 months post transplant
Secondary outcomes:
measure: The proportion of subjects experiencing the composite outcome of death or allograft failure
timeFrame: Up to 12 months post transplant
measure: Number of subjects with biopsy-proven acute T-cell mediated cellular rejection (BP-aTCMR)
timeFrame: Up to 12 months post transplantation
measure: Number of subjects treated for rejection
timeFrame: Up to 12 months post transplantation
measure: Number of subjects treated for acute rejection due to clinical suspicion rather than BP-aTCMR or BP-aABMR within 12 months of transplantation.
timeFrame: Up to 12 months post transplantation
measure: Number of subjects with biopsy-proven active antibody-mediated rejection (BP-aABMR)
timeFrame: Up to 12 months post transplantation
measure: Number of subjects with changes in allograft biopsies for the 5 categories of aTCMR specified in the Banff schema
timeFrame: Up to 12 months post transplantation
measure: Time to changes in allograft biopsies for the 5 categories of aTCMR specified in the Banff schema
timeFrame: Up to 12 months post transplantation
measure: Number of subjects who develop de-novo donor specific antibody (DSA)
timeFrame: Up to 12 months post transplantation
measure: Change in estimated GFR (eGFR)
timeFrame: Baseline and 12 months post transplantation
measure: Number of days to events [TCMR, ABMR, de-novo specific antibodies (DSA) formation, graft loss].
timeFrame: Up to 12 months post transplantation
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Idelberto R Badell, MD
role: PRINCIPAL_INVESTIGATOR
References: