Belatacept With Delayed Tacrolimus Withdrawal Versus Standard-of-Care Tacrolimus in Heart Transplant Recipients (RTB-013)

Plain English Summary

Belatacept in Heart Transplantation is a Phase 2 clinical trial sponsored by National Institute of Allergy and Infectious Diseases (NIAID) studying Heart Transplant. This trial tests a new approach to prevent organ rejection in patients who have received a heart transplant. It is for individuals who have recently had a primary heart transplant. Participants will be randomly assigned to receive either the standard medication or a new regimen involving belatacept with a gradual reduction of another common medication. The standard treatment involves ongoing use of tacrolimus, while the experimental arm aims to reduce reliance on this drug over time. The trial aims to enroll 66 participants.

Official Summary

This is a phase 2, prospective, multi-center, open-label clinical trial. Sixty-six (66) primary heart transplant recipients will be randomized (1:2) to receive either standard-of-care, tacrolimus-based immunosuppression, or a belatacept-based regimen with gradual tacrolimus withdrawal over 9-months post-transplant. Both study arms will receive CellCept® (mycophenolate mofetil- MMF) or Myfortic® (mycophenolate sodium). Corticosteroids will be continued throughout the study in the belatacept arm. The primary objective is to evaluate whether NULOJIX® (belatacept), when implemented with gradual tacrolimus withdrawal over 9 months, is safe with respect to preventing the composite endpoint of acute cellular rejection (ACR) \>= International Society of Heart and Lung Transplantation (ISHLT) 2R, hemodynamic compromise rejection in the absence of a biopsy or histological rejection, re-transplantation, and death at 18 months post-transplant.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are a recipient of a first-time heart transplant and your body has the Epstein-Barr Virus (EBV). You cannot join if you have had a previous organ transplant, have HIV, Hepatitis B or C, or a history of severe allergic reactions to certain medications. You must be able to use effective contraception if you are of childbearing potential. Your kidney function must be reasonably good before the transplant. This trial is studying Heart Transplant, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the new treatment plan can successfully prevent serious rejection of the new heart, the need for another transplant, or death within 18 months after the surgery. The specific primary outcome measures are: Proportion of subjects who experience acute cellular rejection (ACR) >ISHLT 2R (local or core read), hemodynamic compromise (HDC) rejection in the absence of a biopsy or histological rejection, re-transplantation, or death as a composite endpoint. (From randomization to 18 months post-transplantation). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find a safer way to prevent the body from rejecting a new heart by reducing the dose of a common immunosuppressant drug, potentially leading to better long-term kidney health for tr Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Heart Transplant, where improved treatment options are needed.

Investor Insight

This trial explores a novel immunosuppression strategy for a significant post-transplant market, with potential to improve patient outcomes and reduce long-term complications, though it faces competit Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of belatacept compared to standard care. Understand that you will be randomly assigned to one of two treatment groups. You will need to attend regular follow-up appointments and undergo tests for up to 18 months after your transplant. This trial is currently recruiting participants. The trial is being conducted at 5 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 66 participants

Interventions

• DRUG: Belatacept — Patients will receive 10mg/kg on Day 3 post-transplant (72 hours +/- 12 hours post-transplant) Day 7 post-transplant (+/- 6 hours) Day 16 (End of Week 2 after 1st dose of belatacept) post-transplant (+/- 2 days) Day 30 (End of Week 4 after 1st dose of belatacept) post-transplant (+/- 3 days) Day 58 (Week 8) post-transplant (+/- 3 days) Day 86 (Week 12) post-transplant (+/- 3 days) Patients will receive 5mg/kg Every 28 days (+/- 3 days) thereafter
• DRUG: Tacrolimus — Prograf (tacrolimus) or tacrolimus generic
• DRUG: Mycophenolate Mofetil/Sodium — CellCept (mycophenolate mofetil- MMF), or Myfortic (mycophenolate sodium)
• DRUG: Prednisone — Prednisone

Primary Outcomes

• Proportion of subjects who experience acute cellular rejection (ACR) >ISHLT 2R (local or core read), hemodynamic compromise (HDC) rejection in the absence of a biopsy or histological rejection, re-transplantation, or death as a composite endpoint. (From randomization to 18 months post-transplantation)

Secondary Outcomes

• Slope of estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation (From baseline to 18 months post-transplantation, assessed at Baseline, Randomization, Month 1, 6 and 18)
• Proportion of subjects with eGFR <60mL/min/1.73m^2 measured by CKD-EPI (From randomization to 18 months post-transplantation)
• Proportion of subjects with eGFR<45mL/min/1.73m^2 measured by CKD-EPI (From randomization to 18 months post-transplantation)
• Mean change in albumin/creatinine ratio in urine (From baseline to 18 months post-transplantation)
• Change in Chronic Kidney Disease (CKD) stage measured using the mean difference on a continuous measurement scale (From Baseline to 18 months post-transplantation, assessed at Baseline, Month 1, 12 and 18)

Full Eligibility Criteria

Inclusion Criteria:

Study entry

1. Subject must be able to understand the purpose of the study and be willing to participate and provide written consent
2. Recipient of a primary heart transplant (heart transplant only)
3. Epstein-Barr Virus (EBV) seropositive (VCA IgG, EBNA IgG). If EBNA is not available, enrollment may proceed but the result must be available prior to randomization.
4. Agreement to use contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study
5. In the absence of a contraindication, vaccinations must be up to date per the Division of Allergy, Immunology, and Transplantation (DAIT) Vaccination Guidance for Patients in Transplant Trials (niaidtransplantstudies.org)
6. Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted.

Randomization

1. Recipient of a primary heart transplant
2. No desensitization therapy prior to transplant
3. Negative crossmatch actual or virtual, on the most recent sera as determined by the participating study center
4. Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) prior to randomization
5. Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug
6. Pre-transplant eGFR (CKD-epi) \>30ml/min/1.73m\^2. If eGFR \<30ml/min/1.73m\^2 at the time of randomization, participation is permitted if the study physician determines that renal recovery is expected. Participants who are on dialysis at randomization or are expected to require dialysis at or after randomization will not be permitted to participate.

Exclusion Criteria:

Study entry

1. Candidate for multiple solid organ or tissue transplants
2. Prior history of any organ, tissue, or cellular transplant
3. Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period
4. History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies
5. Known hypersensitivity to NULOIX (belatacept) or ORENCIA (Abatacept)
6. Previous treatment with NULOIX (belatacept) or ORENCIA (Abatacept)
7. Epstein Barr Virus (EBV) seronegative or indeterminant
8. Human Immunodeficiency Virus (HIV) positive
9. Hepatitis B surface antigen positive
10. Hepatitis B core antibody positive
11. Hepatitis C virus antibody (HCV Ab+) and hepatitis C virus (HCV) Polymerase Chain Reaction (PCR) positive patients
12. Patients with active Tuberculosis (TB) in the past 2 years, whether or not it was adequately treated; patients with documented treatment of active TB greater than 2 years ago will be allowed to participate if there is documentation of adequate treatment according to locally accepted clinical practice
13. Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant. Testing should be conducted using either a PPD or Interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection (LTBI) must have completed appropriate therapy for LTBI (https://www.cdc.gov/tb/topic/treatment/ltbi.htm). A subject is considered eligible only if they have a negative test for LTBI within one year prior to transplant OR if they have completed appropriate LTBI therapy within one year prior to transplant
14. Positive serology for T. cruzi or known/suspected history of Chagas disease
15. Participants currently or formerly residing in regions of the US that are highly endemic for coccidiomycosis will undergo serological testing, as per the site's standard of care. Participants with positive serology who have previously been fully treated, will be permitted to participate pending full treatment, and then require prophylaxis as further outlined in Section 7 for the duration of the study. Participants with negative serology who reside in regions where coccidiomycosis is endemic are eligible for enrollment only if they receive prophylaxis for the duration of the study. Endemic regions are determined by site based on local standard of care
16. Findings on pre-transplant or pre-randomization chest x-ray or CT scan suggestive of fungal infection where an alternative etiology is not identified. Partici

Trial Locations

• Cedars Sinai Heart Institute/ Cedars Sinai Medical (Site # 71146), Los Angeles, California, United States
• Tampa General Hospital (Site # 71150), Tampa, Florida, United States
• St. Luke's Hospital of Kansas City, Kansas City, Missouri, United States
• NYU Langone Health (Site # 71177), New York, New York, United States
• University of Utah Medical Center (Site # 71126), Salt Lake City, Utah, United States

Frequently Asked Questions

Related Conditions

• Heart Transplant
• Organ Transplantation
• Immunosuppression
• Rejection
• Cardiology
• Nephrology
• Autoimmune Diseases
• Infectious Diseases
• Oncology
• Clinical Trials

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