Clinical trial NCT02604810: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2015-11-13
Enrollment: 53
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval
timeFrame: 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 outcomes:
measure: Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Santa Monica
country: United States
facility: AIRE Medical of Los Angeles
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Miami
country: United States
facility: University of Miami - Batchelor Children's Research Institute
state: Florida
city: North Palm Beach
country: United States
facility: Allergy Associates of The Palm Beaches, PA
state: Florida
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: South Bend
country: United States
facility: The South Bend Clinic
state: Indiana
city: Detroit
country: United States
facility: Children's Hospital of Michigan - Wayne State University
state: Michigan
city: Plymouth
country: United States
facility: Midwest Immunology
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Institute of Allergy and Asthma Clinical Research
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC
state: Oklahoma
city: Hershey
country: United States
facility: Penn State University
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Houston
country: United States
facility: Baylor Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU, VCU Medical Center
state: Virginia
city: Ottawa
country: Canada
facility: Ottawa Hospital, Division of Infectious Disease and Respirology
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
city: Quebec
country: Canada
facility: Clinique d'asthme et d'allergie de Quebec
city: Toronto
country: Canada
facility: The Hospital for Sick Children
Study officials:
References:
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.