IVIG vs SCIG in CIDP

The Influence of Body Composition on Immunoglobulin Disposition After Intravenous and Subcutaneous Administration

Current dosing practices for immunoglobulin G (IgG) may be inadequate in extreme body weight. The current study will evaluate the influence of body composition on intravenous and subcutaneous administration of immunoglobulin G in patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Inflammatory Demyelinating Polyneuropathy; CIDP; Immunoglobulin Deficiency
• Intervention / Treatment: Drug: Intravenous immune globulin G; Drug: Subcutaneous immune globulin G

Detailed Description

Current dosing practices for immunoglobulin G (IgG) may be inadequate in extreme body weight. Total (TBW), ideal (IBW), and adjusted (AdjBW) body weight-based dosing strategies are suggested, but these recommendations are based on expert opinion rather than high quality evidence. The adoption of a specific strategy is highly variable depending on the clinician and/or institutional setting. Recently, payors have also adopted strategies to reduce IgG therapy costs of by capping doses. These recommendations are often based on the presumption that IgG distribution is limited to the vascular space. While this assertion is logical, it does not account for changes adipose tissue may confer on target sites, nor does it account for the potential for adipose tissue to function serve as a metabolic sink or a source of inflammatory mediators. The later would be especially important in patients receiving SCIG. Several observational studies have evaluated IgG dosing in obese patients and have been the source of support for dosing strategies. Many of these studies were not representative of specific populations, contained a wide variety of patients with different IgG indications, and had inadequate serum sampling. More recently, the phase III randomized controlled PATH trial did not find a correlation with serum IgG concentrations and clinical endpoints. However, it is important to note that the study was not designed to evaluate pharmacokinetic and pharmacodynamic endpoints. There is also considerable interpatient variation in response; therefore, identification of patient characteristics that predict response or IgG change from baseline will be a useful tool to improve patient responses. Our study will evaluate the influence of body composition and other patient characteristics may have on IgG exposure when given intravenously or subcutaneously.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Luigi Brunetti, PhD; Phone Number: 2016385868; Email: brunetti@pharmacy.rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers, The State University of New Jersey Clinical Research Center
      • Contact: Luigi Brunetti, PhD; Phone Number: 908-595-2645; Email: luigi.brunetti@rutgers.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged >18 years with a current diagnosis of CIDP (based on European Federation of Neurological sciences / Peripheral Nerve Society CIDP diagnostic criteria).
• 1:1 conversion of IVIG to SCIG (weekly dose conversion) must fall within 0.2-to-0.4 mg/kg dose for SCIG.

Exclusion Criteria:

• Patients receiving IVIG for indications other than CIDP will be excluded.
• Patients with liver impairment (elevations in liver enzymes of greater than 3 times the upper limit of normal) or reduced renal function (CrCl < 50 mL/min) will be excluded
• Active malignancies
• Diabetes
• Myasthenia gravis
• Immunodeficiency
• Autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous immune globulin G; Subjects will receive there current intravenous immune globulin dose.	Drug: Intravenous immune globulin G; Intravenous immune globulin G dosed based on the subjects's current dose received for the treatment of CIDP.; Other Names: Privigen, IVIG
Experimental: Subcutaneous immune globulin G; The dosage will be converted from the subject's current intravenous immune globulin G dosage 1:1 (gm per gm).	Drug: Subcutaneous immune globulin G; Subcutaneous immune globulin G converted from the subject's current IVIG dose 1:1.; Other Names: Hizentra, SCIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of drug half-life	Calculation of drug half-life based on data obtained from serum samples	Through study completion, an average of 4 weeks
Assessment of immune globulin G serum concentration after intravenous immune globulin G administration	Serum IgG concentration (including subtype) will be measured using a human IgG ELISA kit	Just before drug administration, immediately after drug administration, approximately days 7 and 14 post drug administration
Assessment of immune globulin G serum concentration after subcutaneous immune globulin G administration	Serum IgG concentration (including subtype) will be measured using a human IgG ELISA kit	Just before drug administration, immediately after drug administration, approximately days 2, 4 and 7 post drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of grip strength	Grip strength will be measured using the handheld Martin Vigorimeter just before each dose of IgG is administered during the study period. Subjects will be asked to squeeze the dynamometer as hard as possible with each of his or her hands in a standing position.	Baseline and just before administration of next immune globulin dose.
Assessment of muscle function	The Medical Research Council (MRC) system for testing and grading of muscle function aims to provide a standardized and objective way to assess muscle function. It was originally introduced in 1943 and has a long history of use in neurology, rehabilitation and general medicine examinations. Assessments of muscles are done bilaterally, meaning that for each muscle tested, the same muscle on the opposite side of the body is also tested. The MRC sum score is finally calculated by adding the score of each individually assessed muscle. The MRC score ranges from 0 - 30 with 0 as the worst outcome.	Baseline and just before administration of next immune globulin dose.
Assessment of patient disability	The Rasch Overall Disability scale (I-RODS) and the Inflammatory Neuropathy Cause and Treatment Sensory (INCAT) sum score disability scale will be completed before the infusion of IgG. The I-RODS score can range from 0 to 48 with 0 representing the greatest disability. The INCAT score ranges from 0 - 10 with 10 representing worse outcome.	Baseline and just before administration of next immune globulin dose.
Assessment of fatigue	Fatigue is a common patient concern in CIDP and the Rasch-built fatigue severity scale (R-FSS) will be completed before the infusion of IgG. The R-FSS ranges from 9 to 63 with 63 being the worst score	Baseline and just before administration of next immune globulin dose.

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Luigi Brunetti, PhD, Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2022
• Primary Completion (Estimated): October 18, 2024
• Study Completion (Estimated): October 18, 2024

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: obesity; pharmacokinetics; immunoglobulin
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Chronic Disease; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: Pro2019001038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No