search
Back to results

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

Primary Purpose

Primary Immunodeficiency

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
IGIV-C 10%
IGSC 20%
Sponsored by
Grifols Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immunodeficiency

Eligibility Criteria

2 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA Medical Center
  • AIRE Medical of Los Angeles
  • National Jewish Health
  • University of Miami - Batchelor Children's Research Institute
  • Allergy Associates of The Palm Beaches, PA
  • University of South Florida
  • Emory Children's Center
  • Rush University Medical Center
  • The South Bend Clinic
  • Children's Hospital of Michigan - Wayne State University
  • Midwest Immunology
  • Washington University Medical Center
  • Duke University Medical Center
  • Oklahoma Institute of Allergy and Asthma Clinical Research
  • Vital Prospects Clinical Research Institute, PC
  • Penn State University
  • AARA Research Center
  • Baylor Texas Children's Hospital
  • University of Texas Health Science Center at San Antonio
  • Children's Hospital of Richmond at VCU, VCU Medical Center
  • Ottawa Hospital, Division of Infectious Disease and Respirology
  • CHU Sainte-Justine
  • McGill University Health Center
  • Clinique d'asthme et d'allergie de Quebec
  • The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

IGIV-C 10%

IGSC 20%

Arm Description

IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols)

Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%

Full Information

First Posted
November 6, 2015
Last Updated
September 13, 2019
Sponsor
Grifols Therapeutics LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT02604810
Brief Title
Safety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency
Official Title
An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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%.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IGIV-C 10%
Arm Type
Active Comparator
Arm Description
IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols)
Arm Title
IGSC 20%
Arm Type
Experimental
Arm Description
Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols)
Intervention Type
Biological
Intervention Name(s)
IGIV-C 10%
Other Intervention Name(s)
Immune Globulin Injection 10% Caprylate/Chromatography
Intervention Description
IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen
Intervention Type
Biological
Intervention Name(s)
IGSC 20%
Other Intervention Name(s)
Immune Globulin Subcutaneous 20% Caprylate/Chromatography
Intervention Description
IGSC 20% weekly infusions with dose calculated based on previous IgG regimen
Primary Outcome Measure Information:
Title
AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval
Description
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.
Time Frame
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 Measure Information:
Title
Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
AIRE Medical of Los Angeles
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
University of Miami - Batchelor Children's Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Allergy Associates of The Palm Beaches, PA
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
University of South Florida
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Emory Children's Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
The South Bend Clinic
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46617
Country
United States
Facility Name
Children's Hospital of Michigan - Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Midwest Immunology
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55446
Country
United States
Facility Name
Washington University Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oklahoma Institute of Allergy and Asthma Clinical Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73131
Country
United States
Facility Name
Vital Prospects Clinical Research Institute, PC
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Penn State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Baylor Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Children's Hospital of Richmond at VCU, VCU Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Ottawa Hospital, Division of Infectious Disease and Respirology
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C4
Country
Canada
Facility Name
McGill University Health Center
City
Montreal
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Clinique d'asthme et d'allergie de Quebec
City
Quebec
ZIP/Postal Code
G1V 4M6
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
ZIP/Postal Code
M5G 1X8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
31621458
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs