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

Sponsor

Grifols Therapeutics LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04566692

Collaborator

(none)

Enrollment

Locations

Arms

19.5

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency	Biological: IGSC 20%	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 5, 2021

Anticipated Primary Completion Date :

Aug 21, 2022

Anticipated Study Completion Date :

Aug 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment-experienced Cohort Treatment-experienced participants will receive IGSC 20% at 2 different dosing frequencies using a subcutaneous (SC) infusion pump during 2 treatment periods (16 weeks per treatment period). In treatment period 1, treatment-experienced participants will receive 16 weekly IGSC 20% doses from Week 0 to Week 15. For participants entering study on intravenous immune globulin (IVIG), IGSC 20% will be dosed at 1.37 times the equivalent weekly dose and participants entering on subcutaneous immunoglobulin (SCIG) will receive the same milligram/kilogram (mg/kg) equivalent weekly dose as given prior to entry, without using a dose adjustment factor (DAF). In treatment period 2, treatment-experienced participants will receive biweekly IGSC 20 % (i.e, IGSC 20% every 2 weeks) for a total of 9 doses, with the first IGSC 20% dose administered at Week 16 and the final dose given at Week 32.	Biological: IGSC 20% Subcutaneous (SC) infusion pump. Other Names: Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified
Experimental: Treatment-naïve Cohort Treatment-naïve participants will receive a loading dose of 150 mg/kg/day 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 will be administered using an SC infusion pump.	Biological: IGSC 20% Subcutaneous (SC) infusion pump. Other Names: Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified

Arm

Intervention/Treatment

Experimental: Treatment-experienced Cohort

Treatment-experienced participants will receive IGSC 20% at 2 different dosing frequencies using a subcutaneous (SC) infusion pump during 2 treatment periods (16 weeks per treatment period). In treatment period 1, treatment-experienced participants will receive 16 weekly IGSC 20% doses from Week 0 to Week 15. For participants entering study on intravenous immune globulin (IVIG), IGSC 20% will be dosed at 1.37 times the equivalent weekly dose and participants entering on subcutaneous immunoglobulin (SCIG) will receive the same milligram/kilogram (mg/kg) equivalent weekly dose as given prior to entry, without using a dose adjustment factor (DAF). In treatment period 2, treatment-experienced participants will receive biweekly IGSC 20 % (i.e, IGSC 20% every 2 weeks) for a total of 9 doses, with the first IGSC 20% dose administered at Week 16 and the final dose given at Week 32.

Biological: IGSC 20%

Subcutaneous (SC) infusion pump.

Other Names:

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

Experimental: Treatment-naïve Cohort

Treatment-naïve participants will receive a loading dose of 150 mg/kg/day 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 will be administered using an SC infusion pump.

Biological: IGSC 20%

Subcutaneous (SC) infusion pump.

Other Names:

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

Outcome Measures

Primary Outcome Measures

Treatment-experienced Cohort: Area Under Concentration (AUC) of IGSC 20% Administered Weekly Assessed as : Steady-State AUC of Total Immunoglobulin G (IgG) Over a Regular Dosing Interval (τ), Every week (AUC0-τ, weekly or AUC0-7 days) [Pre-dose (within 0.5 hour of infusion start, prior to Week 14 infusion), 1, 3, 4, 5, 7 days, after end of Week 14 infusion (Week 15)]
Treatment-experienced Cohort: AUC of IGSC 20% Administered Biweekly Assessed as Steady-State AUC of Total IgG Over a Biweekly Dosing Interval (AUC0-τ, biweekly or AUC0-14 days) [Pre-dose (within 0.5 hour of infusion start, prior to Week 30 infusion), 1, 3, 4, 7, 11, 14 days after end of Week 30 infusion (Week 32)]

Secondary Outcome Measures

Treatment-experienced Cohort: Steady-State Mean Trough (Predose) Concentration of Total IgG Following SC Administration of IGSC 20% Given IGSC 20% Weekly and Biweekly [Predose on Week 0, 4, 8, 12, 14, 16, 20, 24, 28, 30 and 32]
Treatment-naïve Cohort: Mean Trough Concentration of Total IgG Following IGSC Loading and Maintenance Dose [Predose on Week 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, and 32]
Treatment-naïve Cohort: Individual Trough Concentration of Total IgG Following IGSC Loading and Maintenance Dose [Predose on Week 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, and 32]
Treatment-experienced Cohort: Maximum Concentration (Cmax) of Total IgG at Steady State Given IGSC 20% Weekly and Biweekly [Pre-dose (within 0.5 hour of infusion start, prior to Week 14 infusion), 1, 3, 4, 5, 7 days, post Week 14 infusion (Week 15); Pre-dose (within 0.5 hour of infusion start, prior to Week 30 infusion), 1, 3, 4, 7, 11, 14 days post Week 30 infusion (Week 32)]
Treatment-experienced Cohort: Time to Reach Cmax (tmax) of Total IgG at Steady State Given IGSC 20% Weekly and Biweekly [Pre-dose (within 0.5 hour of infusion start, prior to Week 14 infusion), 1, 3, 4, 5, 7 days, post Week 14 infusion (Week 15); Pre-dose (within 0.5 hour of infusion start, prior to Week 30 infusion), 1, 3, 4, 7, 11, 14 days post Week 30 infusion (Week 32)]
Treatment-experienced and Treatment-naïve Cohorts: Number of Participants with Serious Bacterial Infection (SBI) [Up to Week 33]
Treatment-experienced and Treatment-naïve Cohorts: Number of Participants with All Infections of Any Kind [Up to Week 33]
Treatment-experienced and Treatment-naïve Cohorts: Number of Participants with Validated Infections [Up to Week 33]
Validated infections will be documented by positive radiograph, fever (>38°C oral or >39°C rectal), culture, or diagnostic testing for microorganisms example, bacterial, viral, fungal, or protozoal pathogens (example, rapid streptococcal antigen detection test).
Treatment-experienced and Treatment-naïve Cohorts: Number of Days on Antibiotics [Up to Week 33]
Treatment-experienced and Treatment-naïve Cohorts: Number of Hospitalizations Due to Infection [Up to Week 33]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion Criteria only for Treatment-Experienced Subjects

Subjects 18 years to 75 years (inclusive) at screening
Subjects 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).
Subjects 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.
Subjects currently receiving IgG replacement therapy for ≥3 months via Intravenous (IV) or Subcutaneous (SC) infusion. Subjects receiving Intravenous Immune Globulin (generic terminology) (IVIG) prior to study must receive a dosage of at least 200 milligram per kilogram (mg/kg) per infusion.
Subjects whose screening IgG trough levels must be ≥500 milligram per deciliter (mg/dL).
Subjects have signed an informed consent form.

Inclusion Criteria only for Treatment-Naïve Subjects

Subjects 6 years to 75 years (inclusive) at screening.
Subjects 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).
Subjects have never received IgG replacement treatment (ie, no prior immune globulin replacement therapy).
Subjects whose screening IgG level must be ≤400 mg/dL.
Subjects do not have an SBI nor requires hospitalization for infection of any etiology (example, viral, fungal, parasitic) during screening or at baseline.
Subjects have signed an informed consent.

Exclusion Criteria:

Subjects 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 subject at undue medical risk.
Subjects have had a known serious adverse reaction (AR) to immunoglobulin or any anaphylactic reaction to blood or any blood-derived product.
Subjects 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.
Subjects have known isolated IgG subclass deficiency; isolated specific antibody deficiency (SAD) or selective IgG deficiency; or transient hypogammaglobulinemia of infancy.
Subjects have known Selective Immunoglobulin A (IgA) Deficiency (with or without antibodies to IgA).
Subjects 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]).
Subjects 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.
Subjects have hemoglobin <9 gram per deciliter (g/dL) at screening.
Subjects 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.
Subjects 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]).
Subjects currently have a known hyperviscosity syndrome.
Subjects 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 x109/L]), or human immunodeficiency virus infection/acquired immune deficiency syndrome.
Subjects have a known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection.
Subjects 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 subject. Inhaled or topical corticosteroids are allowed.
Subjects (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 subject has non-controlled arterial hypertension (systolic blood pressure [SBP] >160 millimeter per mercury (mmHg) and/or diastolic blood pressure [DBP] >100 mmHg).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Center of Alabama	Birmingham	Alabama	United States	35209
2	Research Solutions of Arizona, PC	Litchfield Park	Arizona	United States	85340
3	Allergy Associates of The Palm Beaches	North Palm Beach	Florida	United States	33408
4	Allergy & Asthma Clinics of Georgia, P.C.	Albany	Georgia	United States	31707
5	Institute for Asthma and Allergy	Chevy Chase	Maryland	United States	20815
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63141
7	Optimed Research LTD	Columbus	Ohio	United States	43235
8	Allergy, Asthma and Clinical Research Center	Oklahoma City	Oklahoma	United States	73120
9	Oklahoma Institute of Allergy and Asthma Clinical Research	Oklahoma City	Oklahoma	United States	73131
10	Vital Prospect Clinical Research Institute	Tulsa	Oklahoma	United States	74136
11	Allergy anc Clinical Immunology Associates	Pittsburgh	Pennsylvania	United States	15241
12	AARA Research Center	Dallas	Texas	United States	75231