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)

Must not be taking: Biological drugs

Disqualifiers: Invasive fungal infection, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 10-14 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, daratumumab and belatacept (an immunosuppressant), to determine if they can assist individuals struggling to find a compatible kidney donor. Some individuals face challenges in receiving a kidney transplant because their bodies are "highly sensitized," meaning their immune systems react to most donor kidneys. The trial aims to reduce this sensitivity, making it easier and faster to match with a donor. It may suit people on dialysis with end-stage kidney disease who have waited a long time for a transplant due to high sensitization. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both daratumumab and belatacept are being tested for their safety in helping people awaiting kidney transplants. Previous studies have found that patients usually tolerate these drugs well. Daratumumab, often used to treat multiple myeloma, has FDA approval for that purpose, indicating its safety is well understood. Some patients have reported side effects like infusion reactions, but these are usually manageable.

Belatacept is already approved to help prevent organ rejection after a kidney transplant, indicating its safety for patients, though it can sometimes cause side effects like headaches or high blood pressure.

Researchers continue to study the safety of using daratumumab and belatacept together to make kidney transplants more accessible. Early results from similar studies are promising, suggesting the combination is generally safe, but more data is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using the combination of daratumumab and belatacept for kidney transplant candidates because it introduces a novel approach to managing immune response. Unlike standard treatments, which often rely on broad immunosuppressants like tacrolimus or cyclosporine, daratumumab is a monoclonal antibody that specifically targets CD38, potentially offering more precise immune modulation. Belatacept, on the other hand, selectively blocks T-cell activation, further refining the immune system's response after a transplant. This combination could reduce the risk of rejection while minimizing side effects associated with traditional immunosuppressive therapies.

What evidence suggests that this trial's treatments could be effective for highly sensitized kidney transplant candidates?

This trial will study the combination of daratumumab and belatacept for kidney transplant candidates. Research has shown that these drugs might help reduce immune sensitization in people waiting for a kidney transplant, potentially lowering the immune system's reaction to donor kidneys and making it easier to find a match. Early findings suggest that using these drugs together alters immune cells, possibly making them less likely to attack a new kidney. Daratumumab, initially used for treating blood cancers, targets specific immune cells, while belatacept helps manage the immune response during organ transplants. Although this combination is still under investigation in this trial, early results are promising for those having difficulty finding compatible donors. ^{1 2 3 5 6}

Who Is on the Research Team?

Flavio G. Vincenti

Principal Investigator

UCSF Kidney Transplant Research

Are You a Good Fit for This Trial?

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.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept
• Bone marrow aspiration
• Daratumumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Cohort 2 (N=10 Subjects) Experimental Treatment 3 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 Treatment 3 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

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

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Industry Sponsor

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

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

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

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

Bristol-Myers Squibb

Chief Medical Officer since 2024

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

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept and Long-Term Outcomes in Kidney Transplantation. Vincenti, F., Rostaing, L., Grinyo, J., et al.[2022]

Belatacept, a new immunosuppressive drug for kidney transplantation, shows better cardiovascular and metabolic profiles compared to cyclosporin A, including lower blood pressure and serum lipids, and a reduced risk of new onset diabetes after transplantation.

While about 20% of patients on belatacept experienced adverse effects like anemia and infections, it does not appear to increase the risk of infections compared to cyclosporin A, making it a promising option for immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. Ippoliti, G., D'Armini, AM., Lucioni, M., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Belatacept is an effective immunosuppressant for kidney transplant recipients, showing noninferior patient and allograft survival compared to cyclosporine in Phase 3 trials, with improved kidney function over three years.

While belatacept may offer benefits like better renal function and cardiometabolic health, it carries a risk of higher early rejection rates and potential increased risk of posttransplant lymphoproliferative disease, particularly in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. Wojciechowski, D., Vincenti, F.[2018]

Belatacept is as effective as cyclosporine in preventing organ rejection in kidney transplant patients, with similar rates of patient and graft survival and acute rejection, while showing a significant advantage in reducing renal impairment after 12 months.

Patients treated with belatacept experienced fewer serious side effects, including lower rates of new-onset diabetes and better blood pressure and lipid levels compared to those on cyclosporine, indicating a potentially safer profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. Garnock-Jones, KP.[2016]

In a study of 316 kidney transplant recipients over 2 years, belatacept-based immunosuppression showed a significantly lower incidence of reduced kidney function (eGFR <45 ml/min) compared to tacrolimus, indicating better long-term kidney health.

However, belatacept was associated with a higher rate of biopsy-proven acute rejection compared to tacrolimus, suggesting a trade-off between reduced nephrotoxicity and increased rejection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial. Kaufman, DB., Woodle, ES., Shields, AR., et al.[2023]

Converting from tacrolimus to belatacept in kidney transplant patients with stable low eGFR (< 40 mL/min) resulted in a significant improvement in eGFR, with an average increase of 11.0 mL/min compared to 4.8 mL/min in the control group over 4 months.

However, while the belatacept group showed a modest increase in kidney function, there was a higher incidence of acute rejection (16.7%) compared to the control group, indicating potential safety concerns with this conversion strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. Abdelwahab Elhamahmi, D., Heilman, RL., Smith, B., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Citations

1. niaid.nih.gov niaid.nih.gov/clinical-trials/daratumumab-and-belatacept-desensitization

Daratumumab and Belatacept for Desensitization | NIAID The study will evaluate whether the study treatment is safe and can lower the participant's immune system's sensitization to kidney donors.

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04827979

Daratumumab and Belatacept for Desensitization The purpose of this study is to find out whether two drugs, daratumumab (Darzalex®), and belatacept (Nulojix®), can make these kidney transplant candidates ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05145296

NCT05145296 | The Safety/Efficacy Of Daratumumab With ... Evaluate the impact of the dual combination of belatacept and daratumumab on circulating Tfh cells compared to baseline and the end of this dual therapy and at ...

4. immunetolerance.org immunetolerance.org/clinical-trials/daratumumab-plus-belatacept-desensitization-trial-attain

Daratumumab and Belatacept for Desensitization About This Study. ATTAIN is a clinical trial to learn whether a new drug treatment plan can increase the chances for a highly sensitized kidney transplant ...

5. darzalex.com darzalex.com/clinical-results/

Clinical Results 41% (about 4 of 10) of patients responded to treatment with DARZALEX FASPRO ® compared to 37% (about 4 of 10) who responded to treatment with DARZALEX®. In the ...

6. jnj.com jnj.com/media-center/press-releases/darzalex-daratumumab-based-maintenance-regimens-show-clinically-meaningful-deep-and-durable-responses-in-transplant-eligible-patients-with-newly-diagnosed-multiple-myeloma

DARZALEX® (daratumumab)-based maintenance ... Data from the Phase 3 AURIGA study show DARZALEX FASPRO® plus lenalidomide (D-R) maintenance therapy following autologous stem cell transplant ( ...