Clinical trial NCT04566692: A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
Official title: A Multi-center, Single-Sequence, Open-label Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Subjects and Loading/Maintenance Dosing in Treatment-Naïve Subjects With Primary Immunodeficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Immunodeficiency
Keywords: Immunologic Deficiency Syndromes
Immune System Diseases
Immunoglobulins
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2020-09-28
Enrollment: 33
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single sequence crossover design
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria only for Treatment-Experienced Participants

* 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.

Inclusion Criteria only for Treatment-Naïve Participants

* 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).

Primary outcomes:
measure: Treatment-experienced Cohort: AUC of IGSC 20% Administered Weekly Assessed as: Steady-State AUC of Total IgG Over a Regular Dosing Interval (τ)
timeFrame: Predose and post dose at multiple time points after end of infusion up to Week 15
measure: Treatment-experienced Cohort: AUC of IGSC 20% Administered Biweekly Assessed as Steady-State AUC of Total IgG Over a Biweekly Dosing Interval
timeFrame: Predose and post dose at multiple timepoints after end of infusion up to Week 32
Secondary outcomes:
measure: Treatment-experienced Cohort: Cmax of Total IgG at Steady State Following IGSC 20% Weekly and Biweekly Administration
timeFrame: Predose and post dose at multiple timepoints after end of infusion up to Week 32
measure: Treatment-experienced Cohort: Tmax of Total IgG at Steady State Given IGSC 20% Weekly and Biweekly
timeFrame: Predose and post dose at multiple timepoints after end of infusion up to Week 32
measure: Treatment-experienced Cohort: Steady-State Mean Trough Concentration of Total IgG Following IGSC 20% Weekly and Biweekly Administration
timeFrame: Predose and post dose at multiple timepoints after end of infusion up to Week 32
measure: Treatment-experienced Cohort: Individual Trough Concentration of Total IgG Following IGSC 20% Weekly and Biweekly Administration
timeFrame: Screening, IgG Trough 2, Weeks 0, 2, 4, 8, 12, 14 (pre-infusion), 15, 16, 20, 24, 28, 30 (pre-infusion) and 32
measure: Treatment-naïve Cohorts: Individual Trough Concentration of Total IgG
timeFrame: Screening, Weeks 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32
measure: Treatment-experienced and Treatment-naïve Cohorts: Number of Participants With Serious Bacterial Infection (SBI)
timeFrame: From screening up to final follow up visit at Week 33
measure: Treatment-experienced and Treatment-naïve Cohorts: Rate of Events Per Participant Per Year With Infections of Any Kind as Determined by the Investigator
timeFrame: From screening up to final follow up visit at Week 33
measure: Treatment-experienced and Treatment-naïve Cohorts: Rate of Events Per Participant Per Year With Validated Infections
timeFrame: From screening up to final follow up visit at Week 33
measure: Treatment-experienced and Treatment-naïve Cohorts: Rate of Days Per Participant Per Year That Participants Were on Antibiotics
timeFrame: From screening up to final follow up visit at Week 33
measure: Treatment-experienced and Treatment-naïve Cohorts: Rate of Hospitalizations Per Participant Per Year Due to Infection
timeFrame: From screening up to final follow up visit at Week 33
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona, PC
state: Arizona
city: North Palm Beach
country: United States
facility: Allergy Associates of The Palm Beaches
state: Florida
city: Albany
country: United States
facility: Allergy & Asthma Clinics of Georgia, P.C.
state: Georgia
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Optimed Research LTD
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Institute of Allergy and Asthma Clinical Research
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospect Clinical Research Institute
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
Study officials:
References: