The objective of the study is to evaluate the safety and efficacy of eculizumab to prevent AMR in sensitized recipients of living donor kidney transplants requiring desensitization therapy.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and potential efficacy of eculizumab to prevent AMR in
sensitized recipients of living donor kidney transplants requiring
desensitization therapy
Secondary outcome
Cumulative incidence of AMR that occurs between Week 9 and Month 12
post-transplantation
Background summary
Over 25% of kidney transplant candidates have antibodies (are sensitized) to
potential organ donors. As a result, antibody mediated rejection (AMR) has
emerged as a significant clinical problem. Currently, the options to prevent
AMR are limited and marginally successful. No products are approved for the
treatment of AMR. Eculizumab, an inhibitor of C5, has been shown in hypothesis
generating studies to successfully reduce the incidence of AMR following kidney
transplantation of sensitized recipients.
Study objective
The objective of the study is to evaluate the safety and efficacy of eculizumab
to prevent AMR in sensitized recipients of living donor kidney transplants
requiring desensitization therapy.
Study design
It is a randomized, multicenter, open-label, Phase II, two-arm parallel study.
Intervention
Patients will receive one dose of eculizumab approximately one hour prior to
reperfusion of the allograft and will be treated with eculizumab for 9 weeks
post-transplantation OR will be treated post-transplantation with the
transplant center*s SOC for prophylaxis for AMR (control arm).
Study burden and risks
In total over 3 years the patients will undergo the following procedures other
than the Standard Of Care:
Vaccination for Meningitides: 2x (in case the subject received a vaccination
before the enrolment only a booster dose is required)
Kidney biopsy: 5x
Blood drawels: 8x (only Eculizumab-arm)
For the Eculizumab treatment arm: 9x infusion with IP
All other procedures are also performed according to the Standard Of Care. 29
blood drawels will also be performed according the Standard Of Care, however
the blood amount withdrawn for the study can be slightly more (PK samples). The
same amount of hospital visits will be conducted as the Standard of Care,
however the spread of the visits is different.
Possible adverse effects of Eculizumab and performed procedures are:
Adverse effects Eculizumab: headache, higher risk of severe meningococcal
infections; thrombocytopenia, stomach-ache, constipation, vomiting, diarrhoea,
dyspepsia, nausea, chest pain, shivering, infusion related reaction, oedema,
pyrexia, fatigue, herpes simplex, nasopharyngitis, viral infection,
gastroenteritis, bronchitis, sepsis, septic shock, meningococcal sepsis, muscle
pain, back and neck pain, pain in the limbs or joints (arms and legs), muscle
spasm, dizziness, dysgeusia, paresthesia, depression, dysuria, spontaneous
erection of the penis, infection of the upper airways, urinary tract infection,
coughing, pharyngolaryngeal pain, nasal congestion, pruritus, rash, alopecia,
dry skin and hot flashes;
Possible adverse effects of the IV katheter and blood-sampling: bleedings,
bruises, swelling, clots in the vein, leakage of medication or solution in the
surrounding tissue and possibly infection at the insertion site;
Possible adverse effects for the vaccination: temporary local pain or infection
at the administration site;
Possible adverse effects for PP: dizziness, nausea, numb feeling, tingling or a
light-headedness, mild allergic reaction resulting in fever, shivering and
rash, bacterial infection (especially when a central catheter is used), cramps,
numb feeling, bleeding after removal of the clotting drug;
Possible adverse effects for IVIg: functional disorder of or damage to the
kidneys or liver, hypotension, headaches, fatigue, shivering, back pain, leg
cramps, light-headedness, fever, urticaria, hot flashes, nausea or vomiting,
haemolysis, transfusion related lung injury, thrombotic incidents, aseptic
meningitis syndrome and acute or severe kidney failure;
Possible adverse effects of the kidney biopsie: allergic reaction to the
anaesthetic, pain discomfort bleeding or infections at or near the biopsy site,
bleeding from the kidney, hematuria, damage to and loss of the kidney
transplant, death, perforation of internal organs (gallbladder, lung,
intestines or kidney);
Knotter Drive 352
Cheshire CT 06410
US
Knotter Drive 352
Cheshire CT 06410
US
Listed location countries
Age
Inclusion criteria
- Male or female patients * 18 years old;
- Patients with Stage IV or Stage V chronic kidney disease who will receive a kidney transplant from a living donor to whom they are sensitized and require desensitization prior to transplantation;
- Patients must be willing and able to give written informed consent.
Exclusion criteria
- Has received treatment with eculizumab at any time prior to enrolling in this study;
- ABO incompatible with living donor.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-019630-28-NL |
| ClinicalTrials.gov | NCT01399593 |
| CCMO | NL37145.078.11 |