Antibody-mediated Rejection, Humoral Rejection
Conditions
Keywords
Kidney Transplant, Renal Transplant, Rejection, Antibody mediated, Humoral, Eculizumab
Brief summary
This is an open-label analysis that will compare eculizumab versus Plasmapheresis (PP) and Immunoglobulin (IVIg) for the treatment of antibody-mediated rejection (AMR) in renal transplant recipients. All patients will be evaluated from the time of AMR diagnosis for 12 months.
Interventions
Sponsors
Alexion Pharmaceuticals, Inc.
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adult renal transplant recipients, men and women between 18 and 75 years of age. 2. Any patient with acute graft dysfunction (elevation of creatinine above post transplant nadir) AND, two out of three, of the following Inclusion Criteria: 3. Presence of circulating anti human leukocyte antigen (HLA) antibody (DSA donor specific antibody). 4. Histological findings compatible with Banff Class II or III AMR on transplant biopsy. 5. Peritubular capillary c4d positivity on transplant biopsy.
Exclusion criteria
1. Patients that have received eculizumab prior to enrolling in the study. 2. Patients with ongoing non-acute antibody mediated rejection. 3. Patients with predominantly chronic antibody mediated rejection or interstitial fibrosis/tubular atrophy. 4. History of severe cardiac disease (e.g., New York Heart Association \[NYHA\] Functional Class III or IV, myocardial infarction ≤ 6 months of randomization, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases) 5. Prior splenectomy 6. Has a known bleeding disorder 7. Has any active bacterial or other infection which is clinically significant in the opinion of the Investigator and is a contraindication to transplantation 8. Has participated in any other investigational drug study or was exposed to an investigational drug or device within 30 days of screening 9. Has received rituximab (Rituxan®) ≤ 3 months prior to screening 10. Has received bortezomib (Velcade®) ≤ 3 months prior to screening 11. Has received alemtuzumab (Campath®) ≤ 6 months prior to screening 12. Need for concurrent treatment with anti thymocyte globulin (Thymoglobulin®) 13. Hypersensitivity to murine proteins or to one of the product excipients 14. History of illicit drug use or alcohol abuse within the previous year 15. Unresolved meningococcal disease 16. Pregnancy or lactation 17. Current cancer or a history of cancer within the 5 years prior to screening with the exception of patients who have successfully treated non-metastatic basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; or breast carcinoma in situ 18. Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient Active infection with Hepatitis B (HBV), Hepatitis C (HCV) or human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Estimated Glomerular Filtration (eGFR) Rate | Month 3 | Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care * Plasmapheresis (PP) x 3, at 40-60 cc/kg.
* Immunoglobulin (IVIg), to be administered after each PP
Immunoglobulin
Plasmapheresis | 4 |
| Soliris (Eculizumab) * 1200 mg first dose (Time: Screening/Week 0, after Biopsy Proven AMR)
* 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4)
* 1200 mg week 5
* Week 6: If donor specific antibody \< 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9
Eculizumab | 7 |
| Total | 11 |
Baseline characteristics
| Characteristic | Soliris (Eculizumab) | Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 11 Participants |
| Age, Continuous | 43.29 years | 43.25 years | 43.27 years |
| Region of Enrollment United States | 7 participants | 4 participants | 11 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 7 |
| other Total, other adverse events | 3 / 4 | 5 / 7 |
| serious Total, serious adverse events | 3 / 4 | 5 / 7 |
Outcome results
Primary
Percent Change in Estimated Glomerular Filtration (eGFR) Rate
Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Time frame: Month 3
Population: 1 subject in the SOC arm received rescue therapy, per protocol, with eculizumab following PP/IVIg. 1 subject in the Soliris arm received SOC therapy (PP/IVIg) following completion of Soliris treatment period. Both of these subjects received both SOC and Soliris treatment prior to Month 3 protocol biopsy so we have listed their outcome separately.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard of Care | Percent Change in Estimated Glomerular Filtration (eGFR) Rate | -12.92 percent change in eGFR from wk 0 to mo 3 |
| Soliris (Eculizumab) | Percent Change in Estimated Glomerular Filtration (eGFR) Rate | 12.60 percent change in eGFR from wk 0 to mo 3 |
| Standard of Care + Soliris (Eculizumab) | Percent Change in Estimated Glomerular Filtration (eGFR) Rate | 377.25 percent change in eGFR from wk 0 to mo 3 |