Phase 2
N=26
Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant
Kidney Transplant
Bottom Line
View on ClinicalTrials.gov: NCT00670774 ↗Enrolled (actual)
26
Serious AEs
0.0%
Results posted
Jun 2018
Primary outcome: Primary: Number of Subjects With Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation — 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Eculizumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Mark Stegall
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation |
2 | — |
| SECONDARY Number of Patients Developing High DSA Levels at Less Than or Equal to 3 Months |
13 | — |
| SECONDARY Number of Patients Requiring Splenectomy |
— | — |
| SECONDARY Graft Dysfunction in First Month Post Transplant |
0.45 | — |
| SECONDARY Length of Follow-up |
11.9 | — |
| SECONDARY Number of Subjects With Graft Survival at One Year |
16 | — |
| SECONDARY Number of Subjects Receiving Posttransplant Plasma Exchange (PE) |
3 | — |
| SECONDARY Transplant Glomerulopathy Incidence at One Year |
1 | — |
Summary
A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-human leukocyte antigen (HLA) antibody never were able to receive a kidney transplant. Over the past decade, significant progress has been made in overcoming early antibody-mediated renal allograft injury. Our group has performed more than 200 such transplants providing the possibility of transplant to previously untransplantable patients. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection (AHR).
Patients included in this study will be those who have demonstrable anti-HLA antibody specific for their living donor. It is our hypothesis that blockade of terminal complement activation at the time of transplant in combination with our current protocols will reduce the incidence of AHR in patients with anti-donor HLA antibody.
Eligibility Criteria
Inclusion Criteria
- 18 years of age
- Has end stage renal disease (ESRD) and is to receive a kidney transplant from a living donor (LD) to whom he/she has either:
- A positive crossmatch requiring pretransplant desensitization (defined as a positive T-cell FCXM of greater than or equal to 300 but less than 450 prior to desensitization, or as a positive B-cell FCXM of > 300 but < 450 prior to desensitization with demonstrable Class II donor specific alloantibody (DSA) on solid-phase assays). Subsequent to desensitization, patient must have, at the time of transplant, a T-cell and B-cell FCXM less than 300; or
- A positive crossmatch not requiring desensitization (defined as FCXM between 200 and 299)
- Willing to comply with the protocol
- Females of child-bearing potential must have a negative pregnancy test (serum β-HCG) and sexually active females must agree to use a reliable and medically approved method of contraception
- Willing and able to give written informed consent
- Vaccinated against Neisseria meningitides (quadrivalent vaccine), Pneumococcus or H. influenzae at least two weeks prior to beginning desensitization
Exclusion Criteria
- Unstable cardiovascular condition
- Previous splenectomy
- Active bacterial or other infection which is clinically significant in the opinion of the investigator
- Known or suspected hereditary complement deficiency
- Participation in any other investigational drug study or was exposed to an investigational drug or device within 30 days of randomization
- Pregnant, breast-feeding, or intending to conceive during the course of the study, including the two month follow-up period after drug discontinuation
- Known hypersensitivity to the treatment drug or any of its excipients
- History of illicit drug use or alcohol abuse within the previous year
- History of meningococcal disease
- Medical condition that, in the opinion of the investigator, might interfere with the patient's participation in the study, pose an added risk for the patient, or confound the assessment of the patient (e.g. severe cardiovascular or pulmonary disease)
- Previously been enrolled in this trial.
Data sourced from ClinicalTrials.gov (NCT00670774). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.