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

NCT ID: NCT02604810

Last Updated: 2019-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-12-31

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.

Conditions

Primary Immunodeficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IGIV-C 10%

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

Group Type: ACTIVE_COMPARATOR

IGIV-C 10%

Intervention Type: BIOLOGICAL

IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen

IGSC 20%

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

Group Type: EXPERIMENTAL

IGSC 20%

Intervention Type: BIOLOGICAL

IGSC 20% weekly infusions with dose calculated based on previous IgG regimen

Interventions

IGIV-C 10%

IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen

Intervention Type: BIOLOGICAL

IGSC 20%

IGSC 20% weekly infusions with dose calculated based on previous IgG regimen

Intervention Type: BIOLOGICAL

Other Intervention Names

Immune Globulin Injection 10% Caprylate/Chromatography; Immune Globulin Subcutaneous 20% Caprylate/Chromatography

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA Medical Center

Los Angeles, California, United States

AIRE Medical of Los Angeles

Santa Monica, California, United States

National Jewish Health

Denver, Colorado, United States

University of Miami - Batchelor Children's Research Institute

Miami, Florida, United States

Allergy Associates of The Palm Beaches, PA

North Palm Beach, Florida, United States

University of South Florida

St. Petersburg, Florida, United States

Emory Children's Center

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

The South Bend Clinic

South Bend, Indiana, United States

Children's Hospital of Michigan - Wayne State University

Detroit, Michigan, United States

Midwest Immunology

Plymouth, Minnesota, United States

Washington University Medical Center

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Oklahoma Institute of Allergy and Asthma Clinical Research

Oklahoma City, Oklahoma, United States

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, United States

Penn State University

Hershey, Pennsylvania, United States

AARA Research Center

Dallas, Texas, United States

Baylor Texas Children's Hospital

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Children's Hospital of Richmond at VCU, VCU Medical Center

Richmond, Virginia, United States

Ottawa Hospital, Division of Infectious Disease and Respirology

Ottawa, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

McGill University Health Center

Montreal, , Canada

Clinique d'asthme et d'allergie de Quebec

Québec, , Canada

The Hospital for Sick Children

Toronto, , Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 31621458 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GTI1502

Identifier Type: -

Identifier Source: org_study_id