RUCONEST® as a Therapeutic Strategy to Reduce the Incidence of Delayed Graft Function

This is a randomized, single-center double blinded study.

The main objective of this study are to determine the ability of rhC1INH to reduce the
incidence and severity of delayed graft function in comparison to placebo in recipients of
kidneys after cardio-circulatory determination of death (DCD).

This trial has specifically been designed to evaluate the protective effect of rhC1INH
treatment in patients at high risk of developing DGF. The selection of potential donors to be
part of this study will be limited to the population of DCD donors which have historically
shown a risk of developing DGF ranging between 40-55%. Participation in each group will be
randomly assigned. Treatment will be administered by an intra-operative infusion of placebo
or rhC1INH (100 Units/kg) IV followed by twice a day infusion of 50 Units/Kg IV for the
following 48 hours.

A total of 20 subjects will be divided into 2 groups:

Group 1: Control group: standard recipient management + placebo (0.9% Sodium Chloride IV to
equal volume of investigational arm: intraoperatively, and then every 12 hours x 2 = total of
3 doses). treatment (n=10) Group 2: Standard recipient management + 100 U/kg intraoperative
followed by 50 U/kg every 12 hours x 2 = total of 3 doses (200 U/kg).

Max dose 8400 units for the initial dose and 4200 units maximum for the second and third
doses.

Inclusion Criteria:

Adult patients receiving a kidney should satisfy the following to be considered part of the
study:

1. Has the ability to understand the requirements of the study, is able to provide
written informed consent (including consent for the use and disclosure of research
related health information).

2. Male or female at least 18 years of age.

3. Has dialysis dependent renal failure initiated at least 2 months prior to
transplantation.

4. Is to be a recipient of a transplant from a deceased donor (donation after
cardio-circulatory determination of death criteria).

5. Is able to comply with the requirement of antibody induction therapy with rabbit
polyclonal anti-thymocyte globulin or anti-CD25 (anti-IL2R) monoclonal antibodies per
center standard of care.

6. A female subject is eligible to enter the study if she is:

1. Not pregnant or nursing

2. Of non-childbearing potential (i.e., post-menopausal defined as having been
amenorrheic for at least 1 year prior to screening, or has had a bilateral tubal
ligation at least 6 months prior to administration of study drug or bilateral
oophorectomy or complete hysterectomy).

3. If of childbearing potential, must have a negative serum pregnancy test within 48
hours prior to transplant surgery and be using an effective means of
contraception (per the site-specific guidelines or using 2 methods of birth
control concurrently, whichever is more stringent) which will be continued until
the Day 180 visit.

7. Male subjects with female partners of childbearing potential must agree to use an
effective means of contraception (per the site-specific guidelines or use 2 methods of
birth control concurrently, whichever is more stringent), which will be continued
until the Day 180 visit. They will also agree not to donate sperm until 6 months after
dosing.

8. Must be up-to-date on cancer screening according to site-specific guidelines and past
medical history must be negative for biopsy-confirmed malignancy within 5 years of
randomization, with the exception of adequately treated basal cell or squamous cell
carcinoma in situ or carcinoma of the cervix in situ.

9. Must be willing to comply with the protocol procedures for the duration of the study,
including scheduled follow-up visits and examinations.

Exclusion Criteria:

Adult patients receiving a kidney should not have any of the following to be considered
part of the study:

- Use of an investigational drug in the 30 days before surgery.

- Participation in any other research study (drug or non-drug) without prior approval
from the sponsor investigator.

- Recipient of a live donor kidney or a kidney from a brain death donor (DBD) donor.

- Recipient of donor kidney preserved with normothermic machine perfusion.

- Scheduled to undergo multiorgan transplantation.

- Has a planned transplant of kidneys that are implanted en-bloc (dual kidney
transplantation).

- Has planned transplant of dual kidneys (from the same donor) transplanted not en-bloc.

- Has lost first kidney transplant due to graft thrombosis.

- Is scheduled for transplantation of a kidney from a donor who is known to have
received an investigational therapy under another IND/CTA for ischemic/reperfusion
injury immediately prior to organ recovery.

- Known hypersensitivity to human monoclonal antibodies or any of the study drug
excipients.

- Previous hypersensitivity to basiliximab, Campath-1H or antithymocyte globulin (ATG)

- History of or known HIV, HBV (surface antigen), or HCV positivity

- History of malignancy within the last five years, except excised squamous or basal
cell carcinoma of the skin, or cervical intraepithelial neoplasia.

- Presence of clinically significant infections requiring continued therapy.

- Positive screening for active tuberculosis.

- Existence of any surgical or medical condition, other than the current transplantation
which, in the opinion of the investigator, might significantly alter the distribution,
metabolism or excretion of study medication.

- Has a positive T- or B-cell cross-match by NIH anti-globulin lymphocytotoxicity method
or CDC crossmatch method, if performed.

- Has a positive T- or B-cell flow cross-match (over 250 channel shift) AND donor
specific anti-HLA antibody (DSA) detected by flow cytometry (Luminex®) based
antigen-specific anti-HLA antibody testing (over 1000 MFI) or by similar methodology,
if performed.

- History or presence of a medical condition or disease that in the investigator's
assessment would place the patient at an unacceptable risk for study participation.

- Lactating or pregnant woman.

- Patient institutionalized by administrative or court order.

- HLA or ABO incompatible kidney defined as a positive cytotoxic crossmatch or positive
flow cross match.

- Patients with known prothrombotic disorder (e.g. factor V leiden)

- History of thrombosis or hypercoagulable state excluding access clotting

- History of administration of C1INH containing products or recombinant C1INH within 15
days prior to study entry.

- Patient with an abnormal Thromboelastogram- results must be reported out prior to
dosing

- Patients on warfarin or other anti-coagulants or anti-platelets, such as Plavix, low
molecular weight heparin

- Patients with known contraindication to treatment with C1INH

- Patients with abnormal platelet count or known abnormal platelet function function
(PLT>500,000)

- Patients belonging to vulnerable populations: refers to but not limited to children,
minors, pregnant women, prisoners, terminally ill patients, comatose, physically and
intellectually challenged individuals, institutionalized, visual or hearing impaired,
refugees, international research, and educationally disabled healthy volunteers.

Exclusion Criteria for Donor Kidney:

- Donor who is known to have received an investigational drug for I-R injury or graft
rejection (immunosuppressant) in the 48h before organ recovery.

- Participation in any other research study (drug or non-drug).