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

NCT04566692 | Completed Phase 4 Results FDA Drug

• 1 other identifier: GC1906
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 12

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

Keywords

Immunologic Deficiency Syndromes; Immune System Diseases; Immunoglobulins

Outcome Measures

Primary Outcomes (2)

• Treatment-experienced Cohort: AUC of IGSC 20% Administered Weekly Assessed as: Steady-State AUC of Total IgG Over a Regular Dosing Interval (τ)

  Area under the concentration vs. time curve at steady state over the dosing interval (from time 0 to τ), was calculated by a combination of linear and logarithmic trapezoidal methods. The linear trapezoidal method was used for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. The dose interval τ was 7 days for participants on weekly IGSC 20% dosing. The data is reported for participants who received weekly dosing.

  Predose and post dose at multiple time points after end of infusion up to Week 15

• Treatment-experienced Cohort: AUC of IGSC 20% Administered Biweekly Assessed as Steady-State AUC of Total IgG Over a Biweekly Dosing Interval

  Area under the concentration vs. time curve at steady state over the dosing interval (from time 0 to τ), was calculated by a combination of linear and logarithmic trapezoidal methods. The linear trapezoidal method was used for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. The dose interval τ was 14 days for participants on a biweekly IGSC 20% dosing. AUC (0-14 days) for the biweekly dosing were divided by 2 for comparison with AUC(0-7 days) for the weekly dosing prior to the statistical comparison. The data is reported for participants who received bi-weekly dosing.

  Predose and post dose at multiple timepoints after end of infusion up to Week 32

Secondary Outcomes (10)

• Treatment-experienced Cohort: Cmax of Total IgG at Steady State Following IGSC 20% Weekly and Biweekly Administration

  Predose and post dose at multiple timepoints after end of infusion up to Week 32

• Treatment-experienced Cohort: Tmax of Total IgG at Steady State Given IGSC 20% Weekly and Biweekly

  Predose and post dose at multiple timepoints after end of infusion up to Week 32

• Treatment-experienced Cohort: Steady-State Mean Trough Concentration of Total IgG Following IGSC 20% Weekly and Biweekly Administration

  Predose and post dose at multiple timepoints after end of infusion up to Week 32

• Treatment-experienced Cohort: Individual Trough Concentration of Total IgG Following IGSC 20% Weekly and Biweekly Administration

  Screening, IgG Trough 2, Weeks 0, 2, 4, 8, 12, 14 (pre-infusion), 15, 16, 20, 24, 28, 30 (pre-infusion) and 32

• Treatment-naïve Cohorts: Individual Trough Concentration of Total IgG

  Screening, Weeks 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32

Study Arms (2)

IGSC 20%: Treatment-experienced Cohort

EXPERIMENTAL

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.

Biological: IGSC 20%

IGSC 20%: Treatment-naïve Cohort

EXPERIMENTAL

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.

Biological: IGSC 20%

Interventions

IGSC 20% BIOLOGICAL

SC infusion pump.

Also known as: Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified

IGSC 20%: Treatment-experienced Cohort; IGSC 20%: Treatment-naïve Cohort

Eligibility Criteria

• Age: 6 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (12)

Clinical Research Center of Alabama

Birmingham, Alabama, 35209, United States

Location

Research Solutions of Arizona, PC

Litchfield Park, Arizona, 85340, United States

Location

Allergy Associates of The Palm Beaches

North Palm Beach, Florida, 33408, United States

Location

Allergy & Asthma Clinics of Georgia, P.C.

Albany, Georgia, 31707, United States

Location

Institute for Asthma and Allergy

Chevy Chase, Maryland, 20815, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63141, United States

Location

Optimed Research LTD

Columbus, Ohio, 43235, United States

Location

Allergy, Asthma and Clinical Research Center

Oklahoma City, Oklahoma, 73120, United States

Location

Oklahoma Institute of Allergy and Asthma Clinical Research

Oklahoma City, Oklahoma, 73131, United States

Location

Vital Prospect Clinical Research Institute

Tulsa, Oklahoma, 74136, United States

Location

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, 15241, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Interventions

gamma-Globulins; Caprylates

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Rhonda Griffin
• Organization: Grifols Therapeutics LLC

rhonda.griffin@grifols.com

+1 919 757 1744

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single sequence crossover design

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 28, 2020
• Study Start: November 24, 2020
• Primary Completion: July 18, 2022
• Study Completion: July 25, 2022
• Last Updated: September 29, 2023
• Results First Posted: August 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)