A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency

NCT ID: NCT04566692

Last Updated: 2023-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-24
• Study Completion Date: 2022-07-25

Brief Summary

The purpose of the study is to determine whether biweekly (every 2 weeks) administration of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) produces a steady-state area under the concentration versus time curve (AUC) of total Immunoglobulin G (IgG) that is non-inferior to that produced by weekly administration of IGSC 20% in treatment-experienced participants with primary immunodeficiency (PI).

Conditions

Primary Immunodeficiency

Study Design

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

Study Groups

IGSC 20%: Treatment-experienced Cohort

Participants first received 16 weekly doses of IGSC 20% using a subcutaneous (SC) infusion pump from Week 0 to Week 15. Participants entering study on intravenous immune globulin (IVIG), IGSC 20% was dosed at 1.37 times the equivalent weekly dose and participants entering on subcutaneous immunoglobulin (SCIG) received the same milligram/kilogram (mg/kg) equivalent weekly dose as given prior to study entry, without using a dose adjustment factor (DAF). Participants then received 9 biweekly doses of IGSC 20 % (i.e, IGSC 20% every 2 weeks) using an SC infusion pump, with the first IGSC 20% dose administered at Week 16 and the final dose given at Week 32.

Group Type: EXPERIMENTAL

IGSC 20%

Intervention Type: BIOLOGICAL

SC infusion pump.

IGSC 20%: Treatment-naïve Cohort

Treatment-naïve participants received a loading dose of 150 mg/kg/day of IGSC 20% for 5 consecutive days (Week 0, Days 1 to 5) followed by weekly maintenance infusions of 150 mg/kg IGSC 20% starting Week 1 (Day 8) through Week 32. IGSC 20% infusion was administered using an SC infusion pump.

Group Type: EXPERIMENTAL

IGSC 20%

Intervention Type: BIOLOGICAL

SC infusion pump.

Interventions

IGSC 20%

SC infusion pump.

Intervention Type: BIOLOGICAL

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

• Participants 18 years to 75 years (inclusive) at screening
• Participants with documented and confirmed pre-existing diagnosis of Primary Immunodeficiency (PI) with features of hypogammaglobulinemia requiring Immunoglobulin G (IgG) replacement therapy including but not limited to the following humoral-based immunodeficiency syndromes (example, X-linked agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia (example, hyper immunoglobulin M immunodeficiency syndrome).
• Participants have not had an Serious bacterial infection (SBI) or been hospitalized for infection of any etiology (example, viral, fungal, parasitic) within the last 3 months prior to screening or during screening.
• Participants currently receiving IgG replacement therapy for ≥3 months via Intravenous (IV) or SC infusion. Participants receiving IVIG prior to study must receive a dosage of at least 200 mg/kg per infusion.
• Participants whose screening IgG trough levels must be ≥500 milligram per deciliter (mg/dL).
• Participants have signed an informed consent form.

• Participants 6 years to 75 years (inclusive) at screening.
• Participants with documented and confirmed diagnosis of PI with features of hypogammaglobulinemia requiring IgG replacement therapy including but not limited to the following humoral-based immunodeficiency syndromes (example, X-linked agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia (example, hyper immunoglobulin M immunodeficiency syndrome).
• Participants have never received IgG replacement treatment (ie, no prior immune globulin replacement therapy).
• Participants whose screening IgG level must be ≤400 mg/dL.
• Participants do not have an SBI nor requires hospitalization for infection of any etiology (example, viral, fungal, parasitic) during screening or at baseline.
• Participants have signed an informed consent.

Exclusion Criteria

• Participants with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial or place the participant at undue medical risk.
• Participants have had a known serious adverse reaction (AR) to immunoglobulin or any anaphylactic reaction to blood or any blood-derived product.
• Participants who have a 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.
• Participants have known isolated IgG subclass deficiency; isolated specific antibody deficiency (SAD) or selective IgG deficiency; or transient hypogammaglobulinemia of infancy.
• Participants have known Selective Immunoglobulin A (IgA) Deficiency (with or without antibodies to IgA).
• Participants have significant proteinuria (≥3+ or known urinary protein loss >1 gram g/24 hours or nephrotic syndrome), has acute renal failure, is on dialysis, and/or has severe renal impairment on Screening laboratory testing (blood urea nitrogen [BUN] or creatinine more than 2.5 times the upper limit of normal [ULN]).
• Participants have screening values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected normal range for the testing laboratory.
• Participants have hemoglobin <9 gram per deciliter (g/dL) at screening.
• Participants have a history (either 1 episode within the year prior to the Screening Visit or 2 previous episodes over a lifetime) of or current diagnosis of thromboembolism (example, myocardial infarction, cerebrovascular accident or transient ischemic attack) or deep venous thrombosis.
• Participants are currently receiving anti-coagulation therapy which would make SC administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [example, dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa], and parenteral anticoagulants [example, fondaparinux]).
• Participants currently have a known hyperviscosity syndrome.
• Participants have an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/microliter (μL) [1.0 x10^9/L]), or human immunodeficiency virus infection/acquired immune deficiency syndrome.
• Participants have a known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection.
• Participants are 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 participant. Inhaled or topical corticosteroids are allowed.
• Participants (if <18 years of age) have non-controlled arterial hypertension at a level of greater than or equal to the 90th percentile blood pressure (either systolic or diastolic) for their age and height or the adult participant has non-controlled arterial hypertension (systolic blood pressure [SBP] >160 millimeter per mercury (mmHg) and/or diastolic blood pressure [DBP] >100 mmHg).

• Minimum Eligible Age: 6 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

Clinical Research Center of Alabama

Birmingham, Alabama, United States

Research Solutions of Arizona, PC

Litchfield Park, Arizona, United States

Allergy Associates of The Palm Beaches

North Palm Beach, Florida, United States

Allergy & Asthma Clinics of Georgia, P.C.

Albany, Georgia, United States

Institute for Asthma and Allergy

Chevy Chase, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Optimed Research LTD

Columbus, Ohio, United States

Allergy, Asthma and Clinical Research Center

Oklahoma City, Oklahoma, United States

Oklahoma Institute of Allergy and Asthma Clinical Research

Oklahoma City, Oklahoma, United States

Vital Prospect Clinical Research Institute

Tulsa, Oklahoma, United States

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, United States

AARA Research Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GC1906

Identifier Type: -

Identifier Source: org_study_id