Subcutaneous Abatacept in Renal Transplant Recipients

NCT05975450 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00005929U01AI138909
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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?

Conditions

Kidney Transplant Recipient

Keywords

Renal Transplant; abatacept

Outcome Measures

Primary Outcomes (7)

• The proportion of subjects who tolerate subcutaneous injections and are compliant with self-administration

  Measured by abatacept administration logs and autoinjector accountability.

  Throughout the study intervention (up to 12 months)

• 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.

  For-cause biopsies may be performed as dictated by the clinical team. A for-cause biopsy (i.e., graft dysfunction) may be performed in cases of increased serum creatinine, proteinuria, or other clinical symptoms at the discretion of the site Investigator.

  Throughout the study intervention up to 12 months post transplant

• The cumulative incidence of serious adverse events

  Assessments for the development of serious adverse events will be completed at each study visit.

  Throughout the study intervention up to 12 months post transplant

• Incidence of serious infection of special interest

  Any infection requiring hospitalization or prolonged therapy, including but not limited to treatment ≥ 20 days)

  Throughout the study intervention up to 12 months post transplant

• Incidence of patients with cytomegalovirus (CMV) viremia stratified by the magnitude

  All subjects will be monitored for CMV infection by quantitative polymerase chain reaction (PCR) in the blood per the Emory Transplant Center standard of care protocolCMV viremia stratified by count ≥35 but \<10,000 or ≥10, 000

  Throughout the study intervention up to 12 months post transplant

• Incidence of patients with BK viremia stratified by the magnitude

  Undetected, \>0 but \< 1,000, ≥ 1,000 but \<10,000 or ≥ 10,000 - 100,000, ≥100,000 or stratified by log, which is reported as a result.

  Throughout the study intervention up to 12 months post transplant

• Incidence of any malignancy

  Incidence of any malignancy including Post-Transplant Lymphoproliferative Disorder (PTLD)

  Throughout the study intervention up to 12 months post transplant

Secondary Outcomes (10)

• The proportion of subjects experiencing the composite outcome of death or allograft failure

  Up to 12 months post transplant

• Number of subjects with biopsy-proven acute T-cell mediated cellular rejection (BP-aTCMR)

  Up to 12 months post transplantation

• Number of subjects treated for rejection

  Up to 12 months post transplantation

• Number of subjects treated for acute rejection due to clinical suspicion rather than BP-aTCMR or BP-aABMR within 12 months of transplantation.

  Up to 12 months post transplantation

• Number of subjects with biopsy-proven active antibody-mediated rejection (BP-aABMR)

  Up to 12 months post transplantation

Study Arms (1)

Abatacept

EXPERIMENTAL

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.

Drug: Abatacept 125Mg/Ml Syringe

Interventions

Abatacept 125Mg/Ml Syringe DRUG

Participants on qualifying belatacept regimen (with low dose tacrolimus, mmf and prednisone) will have their maintenance regimen changed from i.v. belatacept to s.c. abatacept, which will continue through week 52 (month 12) post-transplant: Costimulation blockade: \- Abatacept 125 mg subcutaneous weekly

Also known as: Orencia

Abatacept

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Idelberto Badell: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Emory Hospital

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

Abatacept; Syringes

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Equipment and Supplies

Study Officials

• Idelberto R Badell, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 3, 2023
• Study Start: August 2, 2023
• Primary Completion: February 14, 2025
• Study Completion: February 14, 2025
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)