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

Primary Immunodeficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02604810
• Other study ID #: GTI1502
• Status: Completed
• Phase: Phase 3
• Start date: January 2016
• Est. completion date: December 2017

Study information

• Verified date: September 2018
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency

Intervention

Biological:
• IGIV-C 10%
IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen
• IGSC 20%
IGSC 20% weekly infusions with dose calculated based on previous IgG regimen

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montreal	Quebec
Canada	McGill University Health Center	Montreal
Canada	Ottawa Hospital, Division of Infectious Disease and Respirology	Ottawa	Ontario
Canada	Clinique d'asthme et d'allergie de Quebec	Quebec
Canada	The Hospital for Sick Children	Toronto
United States	Emory Children's Center	Atlanta	Georgia
United States	Rush University Medical Center	Chicago	Illinois
United States	AARA Research Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Children's Hospital of Michigan - Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Penn State University	Hershey	Pennsylvania
United States	Baylor Texas Children's Hospital	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
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	Oklahoma Institute of Allergy and Asthma Clinical Research	Oklahoma City	Oklahoma
United States	Midwest Immunology	Plymouth	Minnesota
United States	Children's Hospital of Richmond at VCU, VCU Medical Center	Richmond	Virginia
United States	Washington University Medical Center	Saint Louis	Missouri
United States	University of South Florida	Saint Petersburg	Florida
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	AIRE Medical of Los Angeles	Santa Monica	California
United States	The South Bend Clinic	South Bend	Indiana
United States	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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