Safety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency

An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency

This study was designed to determine a dose of weekly subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols) (IGSC 20%) that produces steady-state AUC of total IgG that was non-inferior to that of the regularly administered intravenous dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols) (IGIV-C 10%) in primary immunodeficiency subjects. This study was also designed to determine steady state trough total IgG levels after IGSC 20% infusion and after IGIV-C 10% infusion for comparison and to assess the safety and tolerability of IGSC 20%.

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency
• Intervention / Treatment: Biological: IGIV-C 10%; Biological: IGSC 20%

Detailed Description

This was a prospective, multi-center, open-label, single-sequence, 6-month, pharmacokinetic, safety and tolerability study of IGSC 20% in subjects with primary immunodeficiency. Approximately 50 subjects were to be enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 2-16 years) completing treatment with subcutaneously administered IGSC 20%.

This study included 3 treatment phases: Run-In Phase, IV Phase (IV administration of IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%).

Subjects, depending on their current IgG treatment regimen, might be required to enter the Run-In Phase to receive IV IGIV-C 10% treatment (Sponsor provided) to achieve an approximately steady-state condition prior to entering the IV Phase. They then entered the IV Phase to determine the AUC profiles of IV infusions of IGIV-C 10%.

Subjects with a qualifying IV IGIV-C 10% treatment regimen (on stable IGIV-C 10% doses of 300-800 mg/kg) entered the IV Phase directly where they will receive IGIV-C 10%. In the IV Phase, steady-state IV PK assessments, including AUC, were to be performed.

After completing the IV Phase, subjects entered the SC Phase to receive weekly SC doses of IGSC 20% for at least 24 weeks.

The PK profiles of total IgG following administration of both IV (IGIV-C 10%) administration and SC (IGSC 20%) administration were determined and compared after reaching approximate steady-state conditions.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada, H4A 3J1
    • McGill University Health Center
  • Quebec, Canada, G1V 4M6
    • Clinique d'asthme et d'allergie de Quebec
  • Toronto, Canada, M5G 1X8
    • The Hospital for Sick Children
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital, Division of Infectious Disease and Respirology
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C4
      • CHU Sainte-Justine
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Santa Monica, California, United States, 90404
      • AIRE Medical of Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Batchelor Children's Research Institute
    • North Palm Beach, Florida, United States, 33408
      • Allergy Associates of The Palm Beaches, PA
    • Saint Petersburg, Florida, United States, 33701
      • University Of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Children's Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • South Bend, Indiana, United States, 46617
      • The South Bend Clinic
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan - Wayne State University
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Midwest Immunology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73131
      • Oklahoma Institute of Allergy and Asthma Clinical Research
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute, PC
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Houston, Texas, United States, 77030
      • Baylor Texas Children's Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU, VCU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pre-existing diagnosis of primary immunodeficiency with features of hypogammaglobulinemia requiring IgG replacement therapy
• No serious bacterial infection within the last 3 months prior to or during Screening
• Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 consecutive months. Subjects receiving IGIV must be receiving a dosage of 300 to 800 mg/kg per infusion
• Documented (at least once within previous 3 months) IgG trough level of ≥500 mg/dL on current IgG replacement therapy regimen

Exclusion Criteria:

• Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
• History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study
• Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
• Nephrotic syndrome, and/or a history of acute renal failure and/or severe renal impairment, and/or on dialysis
• History (year prior to Screening or 2 episodes in lifetime ) of or current diagnosis of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular accident or transient ischemic attack)
• Acquired medical condition known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/μL [1.0 x 10^9/L]), or human immunodeficiency virus infection/acquired immune deficiency syndrome
• Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
• Non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg in adult subjects)
• Receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents, (b) immunomodulators, (c) long-term systemic corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for>30 days Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. Inhaled or topical corticosteroids are allowed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IGIV-C 10%; IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols)	Biological: IGIV-C 10%; IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen; Other Names: Immune Globulin Injection 10% Caprylate/Chromatography
Experimental: IGSC 20%; Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols)	Biological: IGSC 20%; IGSC 20% weekly infusions with dose calculated based on previous IgG regimen; Other Names: Immune Globulin Subcutaneous 20% Caprylate/Chromatography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval	The primary PK endpoint (steady-state AUC values) analysis was performed using analysis of variance (ANOVA) using PK data from a total of 49 subjects from the IV phase and 39 subjects from the SC phase.	For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%	For intravenous infusion, pre-dose at Week 1 and Week 3 or Week 4 and for subcutaneous infusion, predose at Weeks 13, 14, 17, and 21

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Publications and helpful links

General Publications

• Sleasman JW, Lumry WR, Hussain I, Wedner HJ, Harris JB, Courtney KL, Mondou E, Lin J, Stein MR. Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. Immunotherapy. 2019 Nov;11(16):1371-1386. doi: 10.2217/imt-2019-0159. Epub 2019 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: November 11, 2015
• First Posted (Estimate): November 13, 2015

Study Record Updates

• Last Update Posted (Actual): October 4, 2019
• Last Update Submitted That Met QC Criteria: September 13, 2019
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: GTI1502

Drug and device information, study documents

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