Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant

The eculizumab dosing regimen was modified from that used in the treatment of paroxysmal
nocturnal hemoglobinuria and consisted of 1200 mg immediately prior to transplantation, 600
mg on postoperative day 1, and 600 mg weekly thereafter for 4 weeks. At week 4, assessment of
DSA levels was performed. Eculizumab was discontinued in patients whose DSA had significantly
decreased (B flow crossmatch channel shift<200). In patients with persistently high DSA and
thus believed to have continued high risk for AMR, eculizumab treatment continued (1200 mg
week 5, and then every 2 weeks). Another DSA assessment was performed at week 9 and
eculizumab was discontinued if the B flow crossmatch channel shift was <200.

The eculizumab group were compared to a historical control group consisting of consecutive
transplants between 1/1/2005 and 1/10/2017 who met the inclusion criteria. The historical
control group had been treated with a similar plasma exchange based protocol without
eculizumab.

Inclusion Criteria:

1. 18 years of age

2. Has end stage renal disease (ESRD) and is to receive a kidney transplant from a living
donor (LD) to whom he/she has either:

1. 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

2. A positive crossmatch not requiring desensitization (defined as FCXM between 200
and 299)

3. Willing to comply with the protocol

4. 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

5. Willing and able to give written informed consent

6. Vaccinated against Neisseria meningitides (quadrivalent vaccine), Pneumococcus or H.
influenzae at least two weeks prior to beginning desensitization

Exclusion Criteria:

1. Unstable cardiovascular condition

2. Previous splenectomy

3. Active bacterial or other infection which is clinically significant in the opinion of
the investigator

4. Known or suspected hereditary complement deficiency

5. Participation in any other investigational drug study or was exposed to an
investigational drug or device within 30 days of randomization

6. Pregnant, breast-feeding, or intending to conceive during the course of the study,
including the two month follow-up period after drug discontinuation

7. Known hypersensitivity to the treatment drug or any of its excipients

8. History of illicit drug use or alcohol abuse within the previous year

9. History of meningococcal disease

10. 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)

11. Previously been enrolled in this trial.