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

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

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

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: LFG316; Drug: IVIG

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LFG316 + IVIG	Drug: LFG316; LFG316 single dose; Drug: IVIG; IVIG single dose
Experimental: LFG316 alone	Drug: LFG316; LFG316 single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Pharmacokinetics (PK) of LFG316: Area Under the Plasma Concentration-time Curve (AUC)	The following PK parameters were determined from the plasma concentration time profile of LFG316 using a non-compartmental method: AUClast: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration AUCinf: Area under the plasma concentration-time curve from time zero to infinity	1 month
Plasma Pharmacokinetics (PK) of LFG316: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)		1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events as a measure of safety and tolerability	2 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com
• Results for CLFG316B2101 can be found on Novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2016
• Primary Completion (Actual): July 19, 2017
• Study Completion (Actual): July 19, 2017

Study Registration Dates

• First Submitted: August 22, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (Estimate): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: CLFG316B2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No