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

NCT02878616 | Completed Phase 1 FDA Drug

• 1 other identifier: CLFG316B2101
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Conditions

Kidney Transplantation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of patients with adverse events as a measure of safety and tolerability

  2 months

Study Arms (2)

LFG316 + IVIG

EXPERIMENTAL

Drug: LFG316; Drug: IVIG

LFG316 alone

EXPERIMENTAL

Drug: LFG316

Interventions

LFG316 DRUG

LFG316 single dose

LFG316 + IVIG; LFG316 alone

IVIG DRUG

IVIG single dose

LFG316 + IVIG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men or women 18-70 years of age suffering from end-stage renal disease and who are on chronic dialysis therapy.
• Candidates for kidney transplantation who are pre-sensitized and will be undergoing desensitization therapy.
• Written informed consent must be obtained before any assessment is performed.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study.
• Recipients who are ABO compatible with donor allograft.
• 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.
• 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.

You may not qualify if:

• Patients requiring or undergoing peritoneal dialysis.
• Patients with a known contraindication to treatment with blood products.
• Patients with a known pro-thrombotic disorder and/or history of thrombosis or hyper-coagulable state, excluding hemodialysis venous access clotting.
• 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.
• Patients at risk for tuberculosis (TB)
• 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.
• Pregnant or nursing (lactating) women.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• 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.

  PMID: 32301258 DERIVED

Related Links

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

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: August 25, 2016
• Study Start: August 26, 2016
• Primary Completion: July 19, 2017
• Study Completion: July 19, 2017
• Last Updated: December 11, 2020

Record last verified: 2018-07

Locations

US (1)