Clinical trial NCT02878616: Study in End-stage Renal Disease Patients Awaiting Kidney Transplant to Investigate the Potential Effect of IVIG Treatment on the Pharmacokinetics and Pharmacodynamics of LFG316
Official title: Open-label, Parallel-group, Drug-drug Interaction Study in End-stage Renal Disease Patients Awaiting Kidney Transplant to Investigate the Potential Effect of IVIG Treatment on the Pharmacokinetics and Pharmacodynamics of LFG316
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Transplantation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-08-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigate whether concomitant treatment with intravenous immunoglobulin (IVIG) can alter the pharmacokinetics and pharmacodynamics of LFG316 to an extent which would necessitate dose adaptation for LFG316 in pre-sensitized end-stage renal disease patients awaiting kidney transplantation


Eligibility criteria: Inclusion Criteria:

1. Adult men or women 18-70 years of age suffering from end-stage renal disease and who are on chronic dialysis therapy.
2. Candidates for kidney transplantation who are pre-sensitized and will be undergoing desensitization therapy.
3. Written informed consent must be obtained before any assessment is performed.
4. Able to communicate well with the investigator, to understand and comply with the requirements of the study.
5. Recipients who are ABO compatible with donor allograft.
6. Patients awaiting kidney allograft from a living or deceased donor. For patients awaiting transplant from a living donor, kidney transplantation must only occur after 28 days post-LFG316 infusion.
7. History of vaccination with meningococcus and pneumococcus between 2 weeks and 36 months prior to dosing. Documentation is required. If patients have not been vaccinated, they must be vaccinated at least 2 weeks prior to dosing. The choice of vaccine(s) should take into account the serotypes prevalent in the geographic areas in which study patients will be enrolled.

Exclusion Criteria:

1. Patients requiring or undergoing peritoneal dialysis.
2. Patients with a known contraindication to treatment with blood products.
3. Patients with a known pro-thrombotic disorder and/or history of thrombosis or hyper-coagulable state, excluding hemodialysis venous access clotting.
4. Patients who have positive PCR results for hepatitis B and/or hepatitis C, and/or history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
5. Patients at risk for tuberculosis (TB)
6. Patients with any severe, progressive or uncontrolled acute or chronic medical condition not related to end-stage renal disease (such as uncontrolled infectious disease or sepsis), clinical laboratory abnormalities at screening or baseline that in the investigator's opinion would make the patient inappropriate for entry into this study, or known active presence of malignancies.
7. Pregnant or nursing (lactating) women.
8. Women of child-bearing potential, unless highly effective methods of contraception are used during dosing and for 50 days after the last dose of LFG316, or sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 50 days after the last dose of LFG316.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Plasma Pharmacokinetics (PK) of LFG316: Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: 1 month
measure: Plasma Pharmacokinetics (PK) of LFG316: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
timeFrame: 1 month
Secondary outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability
timeFrame: 2 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
Study officials:
References:
citation: Jordan SC, Kucher K, Bagger M, Hockey HU, Wagner K, Ammerman N, Vo A. Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti-C5 monoclonal antibody tesidolumab. Am J Transplant. 2020 Sep;20(9):2581-2588. doi: 10.1111/ajt.15922. Epub 2020 May 13.