15 Participants Needed

Daratumumab + Belatacept for Kidney Transplant Candidates

(ATTAIN Trial)

Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

Some kidney transplant candidates have a very low chance of getting a kidney transplant because their immune systems are "highly sensitized" to most kidney donors. Being "highly sensitized" means that they will likely have to wait a long time (more than 5 years) before an acceptable donor is found for them or, they never receive a compatible donor, and die on waitlist. The purpose of this study is to find out whether two drugs, daratumumab (Darzalex®), and belatacept (Nulojix®), can make these kidney transplant candidates less sensitized, and make it easier and quicker to find a kidney donor for them.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently on a biological drug, you cannot participate in the trial.

What data supports the effectiveness of the drug Belatacept for kidney transplant candidates?

Research shows that Belatacept is an effective alternative to other drugs for kidney transplant patients, improving kidney function and reducing the risk of diabetes and high blood pressure compared to cyclosporine.12345

Is the combination of Daratumumab and Belatacept safe for kidney transplant candidates?

Belatacept, used in kidney transplants, is generally well tolerated but can cause side effects like anemia, fever, and infections. It may also increase the risk of certain cancers and serious infections, especially in patients without prior exposure to the Epstein-Barr virus. Daratumumab's safety profile is not detailed here, but it is important to consult with healthcare providers for comprehensive safety information.14678

How is the drug combination of Daratumumab and Belatacept unique for kidney transplant candidates?

The combination of Daratumumab and Belatacept is unique because Belatacept is a novel immunosuppressive drug that helps prevent organ rejection by blocking T-cell activation, potentially reducing long-term kidney damage compared to traditional treatments. This combination may offer a new approach by integrating Daratumumab, which is typically used in other conditions, to enhance the effectiveness of Belatacept in kidney transplants.13468

Research Team

FG

Flavio G. Vincenti

Principal Investigator

UCSF Kidney Transplant Research

Eligibility Criteria

This trial is for kidney transplant candidates who are highly sensitized (cPRA ≥99.9% or >98% with long wait times) and on hemodialysis, able to consent, HIV and Hepatitis C negative, immune to certain viruses like EBV and TB, not pregnant or nursing, willing to use contraception. Excluded are those with serious diseases besides kidney failure, past transplants or immunodeficiencies, recent infections requiring hospitalization or antibiotics.

Inclusion Criteria

Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing
I understand the study and can give my consent.
I am on the UNOS list for a transplant with a high antibody level or long wait time.
See 17 more

Exclusion Criteria

Previous non-kidney solid organ or bone marrow transplant
Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
Past or current medical problems or findings from physical examination or laboratory testing not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, interfere with the subject's ability to comply with study requirements, or impact the quality or interpretation of the data obtained from the study
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infusions of daratumumab and belatacept over a 10-week period in Cohort 1 or a 14-week period in Cohort 2

10-14 weeks
Weekly visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including HLA antibody assessments and bone marrow aspiration

42-56 weeks
Regular follow-up visits

Post-transplant Follow-up

Participants who receive a kidney transplant are monitored for 52 weeks post-transplant

52 weeks

Treatment Details

Interventions

  • Belatacept
  • Bone marrow aspiration
  • Daratumumab
Trial OverviewThe study tests if daratumumab (Darzalex®) and belatacept (Nulojix®), along with a bone marrow aspiration procedure can reduce the immune system's sensitivity in prospective kidney transplant recipients making it easier for them to find compatible donors.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Cohort 2 (N=10 Subjects)Experimental Treatment3 Interventions
The enrollment of ten additional subjects is dependent on the results in Cohort 1. Multiple intravenous infusions of daratumumab and belatacept over 14 weeks:° * Daratumumab will be administered intravenously at a dose of 8 mg/kg for the first dose, then 16 mg/kg for subsequent given weekly for 3 weeks, then every 2 weeks for 2 doses (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, 14, 16 and 18). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%. * Was modified based on the safety and efficacy analysis of Cohort 1.
Group II: Cohort 1 (N=5 Subjects)Experimental Treatment3 Interventions
Multiple intravenous infusions of daratumumab and belatacept over 10 weeks: * Daratumumab will be administered intravenously at a dose of 8 mg/kg weekly for 4 weeks, then every other week for 4 weeks (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, and 14). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit, and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%.

Belatacept is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Nulojix for:
  • Prophylaxis of organ rejection in adult patients receiving a kidney transplant
🇪🇺
Approved in European Union as Nulojix for:
  • Prophylaxis of organ rejection in adult patients receiving a kidney transplant

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials
167
Recruited
38,000+
David Simmons profile image

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer profile image

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

Immune Tolerance Network (ITN)

Collaborator

Trials
68
Recruited
7,900+

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials
44
Recruited
15,000+

PPD

Industry Sponsor

Trials
162
Recruited
36,600+
Dr. Austin Smith profile image

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons profile image

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Bristol-Myers Squibb

Industry Sponsor

Trials
2,731
Recruited
4,127,000+
Headquarters
New York City, USA
Known For
Oncology & Cardiovascular
Top Products
Eliquis, Opdivo, Revlimid, Orencia
Christopher Boerner profile image

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt profile image

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Early conversion to belatacept-based immunosuppression after kidney transplantation significantly improved kidney function, as measured by eGFR, from 26.73 to 45.3 ml/min/1.73 m² within one year, while late conversion showed no significant change.
Both early and late conversion groups had a one-year allograft survival rate of 100%, but early conversion was associated with a higher rate of acute T-cell-mediated rejections, suggesting that the choice of immunosuppressants may influence rejection types.
Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients.Moein, M., Dvorai, RH., Li, BW., et al.[2023]
In a study involving 666 kidney-transplant recipients over 7 years, both more-intensive and less-intensive belatacept regimens significantly reduced the risk of death or graft loss by 43% compared to cyclosporine.
Patients receiving belatacept also experienced improved renal function, as indicated by an increase in mean estimated glomerular filtration rate (eGFR), while those on cyclosporine showed a decline in eGFR.
Belatacept and Long-Term Outcomes in Kidney Transplantation.Vincenti, F., Rostaing, L., Grinyo, J., et al.[2022]
Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.
In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.
Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy.Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

References

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. [2023]
Belatacept and Long-Term Outcomes in Kidney Transplantation. [2022]
Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. [2020]
Belatacept: in adult kidney transplant recipients. [2016]
Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. [2022]
Belatacept in kidney transplantation. [2018]
Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. [2023]
Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial. [2023]