Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation
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ClinicalTrials.gov Identifier: NCT03388008 |
Recruitment Status
:
Not yet recruiting
First Posted
: January 2, 2018
Last Update Posted
: January 2, 2018
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Condition or disease | Intervention/treatment | Phase |
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Lung Transplant Rejection Antibody-mediated Rejection | Drug: Belatacept Drug: Tacrolimus Drug: ATG Drug: Mycophenolate Mofetil Drug: Methylprednisolone Drug: Prednisone | Phase 2 |
Lung transplantation is the ultimate treatment for patients with advanced lung disease. However, long-term outcomes remain disappointing and the median survival after transplantation is approximately 5.5 years. Beyond the first year after transplantation, chronic lung allograft dysfunction is the leading cause of death. The exact mechanisms that lead to chronic lung allograft dysfunction are unclear, but the development of donor-specific HLA antibodies is an independent risk factor. In fact, studies have consistently identified the development of donor-specific HLA antibodies as a significant and independent risk factor for chronic lung allograft dysfunction and mortality after transplantation.
Belatacept is a CTLA4-Ig fusion protein that binds CD80 and CD86 thereby blocking CD28 co-stimulatory signals. Belatacept has been extensively studied in kidney transplantation. In a long-term study, patients treated with Belatacept had better survival than those treated with Cyclosporine. Importantly, Belatacept-treated patients were significantly less likely to develop donor-specific HLA antibodies than Cyclosporine-treated patients. Nonetheless, Belatacept has not been formally evaluated after lung transplantation. The investigators hypothesize that Belatacept-based immunosuppression would result in a lower incidence of donor-specific HLA antibodies and that this would result in better chronic lung allograft dysfunction-free survival after transplantation. Before conducting a large scale randomized controlled trial to test this hypothesis, the investigators plan to conduct the current pilot randomized controlled trial to examine the feasibility of conducting the large scale randomized controlled trial.
The investigators plan to enroll and randomize 40 lung transplant recipients at 2 sites. All recipients will be treated with anti-thymocyte globulin for induction immunosuppression. Those randomized to standard of care immunosuppression will be treated with Tacrolimus, Mycophenolate mofetil, and prednisone. Those randomized to Belatacept-based immunosuppression will be treated with Belatacept, Tacrolimus, and prednisone for the first 89 days; on day 90, Mycophenolate mofetil will be substituted for Tacrolimus and patients will be continued on Belatacept, Mycophenolate mofetil, and prednisone for the remainder of year 1 after transplantation.
Patients in both groups will be monitored closely for episodes of acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection with surveillance bronchoscopy and transbronchial lung biopsies on days 28, 84, 112, 168, 252, and 365 (± 7 days) as part of the sites' routine clinical protocols. In addition, patients will be monitored for the development of donor-specific HLA antibodies with routine blood tests on on days 10 (± 3 days), 28, 56, 84, 112, 168, 252, and 365 (± 7 days).
The primary endpoint of the study is a composite of the development of donor-specific HLA antibodies, re-transplantation, and death. Secondary endpoints include acute cellular rejection, lymphocytic bronchiolitis, antibody-mediated rejection, chronic lung allograft dysfunction, survival, cytomegalovirus infection, bacterial infection, community-acquired respiratory viral infection, chronic kidney disease stage 3, malignancy, hypertension, diabetes, and hypercholesterolemia.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 40 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Study participants will be randomized to 1 of 2 arms: Belatacept-based immunosuppression or standard of care immunosuppression |
Masking: | Single (Outcomes Assessor) |
Masking Description: | Investigators examining lung biopsy results and blood for the development of donor-specific HLA antibodies will be blinded to study participants' treatment arm assignment. |
Primary Purpose: | Treatment |
Official Title: | A Pilot Randomized Controlled Trial of De Novo Belatacept-Based Immunosuppression in Lung Transplantation |
Estimated Study Start Date : | June 1, 2018 |
Estimated Primary Completion Date : | January 31, 2021 |
Estimated Study Completion Date : | April 30, 2021 |

Arm | Intervention/treatment |
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Active Comparator: Standard of care
Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365
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Drug: Tacrolimus
Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml
Other Name: Prograf
Drug: ATG
Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation
Other Name: Thymoglobulin
Drug: Mycophenolate Mofetil
Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation
Other Name: Cellcept, Myfortic
Drug: Methylprednisolone
Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses
Other Name: Solumedrol
Drug: Prednisone
Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
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Experimental: Belatacept-based immunosuppression
Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365
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Drug: Belatacept
Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364)
Other Name: Nulojix
Drug: ATG
Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation
Other Name: Thymoglobulin
Drug: Mycophenolate Mofetil
Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation
Other Name: Cellcept, Myfortic
Drug: Methylprednisolone
Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses
Other Name: Solumedrol
Drug: Prednisone
Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
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- Donor-specific HLA antibodies, re-transplantation, or death [ Time Frame: 365 days ]Composite primary endpoint

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Ages Eligible for Study: | 18 Years to 70 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Provided written informed consent for study participation
- Underwent single or bilateral lung transplantation
- Negative urine pregnancy test for women of child bearing potential and willingness to use highly-effective contraception
Exclusion Criteria:
- Requiring invasive mechanical ventilation immediately before transplantation
- Requiring extracorporeal life support (ECLS) (i.e., ECMO) immediately before transplantation
- Received treatment to deplete HLA antibodies before transplantation to improve the possibility of transplantation
- Having DSA immediately before transplantation (i.e., positive virtual crossmatch)
- Listed for multi-organ transplant (e.g., heart-lung, liver-lung, kidney-lung)
- Pregnant or breast-feeding
- Active infection with Hepatitis B or C virus
- Active infection with human immunodeficiency virus (HIV)
- Chronic infection with Burkholderia cepacia complex before transplantation
- Epstein Barr Virus (EBV) seronegative status
- Participation in another interventional clinical trial
- Allograft dysfunction requiring ECMO support after transplantation
- Delayed chest closure after transplantation
- Severe coagulopathy and significant bleeding in the opinion of the PI
- Any condition that in the opinion of the site PI introduces undue risk by participating in this study

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03388008
Contact: Ramsey R Hachem, MD | (314) 454-8766 | Rhachem@wustl.edu | |
Contact: Katina Richardson | (314) 454-8766 | k.richardson@wustl.edu |
United States, Texas | |
Baylor University Medical Center at Dallas | Not yet recruiting |
Dallas, Texas, United States, 75246 | |
Contact: Howard Huang, MD 214-820-7856 Howard.Huang@BSWHealth.org |
Principal Investigator: | Ramsey R Hachem, MD | Washington University School of Medicine |
Documents provided by Ramsey Hachem, Washington University:
Publications:
Responsible Party: | Ramsey Hachem, Professor of Medicine, Washington University |
ClinicalTrials.gov Identifier: | NCT03388008 History of Changes |
Other Study ID Numbers: |
Bela Lung Pilot |
First Posted: | January 2, 2018 Key Record Dates |
Last Update Posted: | January 2, 2018 |
Last Verified: | December 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No | |
Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by Ramsey Hachem, Washington University:
donor-specific HLA antibodies lung transplantation |
Additional relevant MeSH terms:
Prednisolone acetate Methylprednisolone acetate Prednisone Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone Prednisolone hemisuccinate Prednisolone phosphate Mycophenolic Acid Tacrolimus Thymoglobulin Abatacept Anti-Inflammatory Agents Glucocorticoids Hormones |
Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Antiemetics |