A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Immune Globulin (Human) 10% (Gamunex-C) PEG Process (IVIG-PEG) Compared to Gamunex-C in Participants With Primary Humoral Immunodeficiency

Primary Immunodeficiency Clinical Trial

Official title:

A Phase 3, Multicenter, Open-label, Single-sequence, Cross-over, Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of IVIG-PEG Compared to Gamunex-C in Subjects With Primary Humoral Immunodeficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04561115
• Other study ID #: GC1902
• Status: Completed
• Phase: Phase 3
• Start date: September 2, 2020
• Est. completion date: March 28, 2022

Study information

• Verified date: June 2023
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate bioequivalence of IVIG-PEG with Gamunex-C (IVIG-C) at steady-state as determined by comparing total Immunoglobulin G (IgG) area under the concentration-time curve during the defined dosing interval ([AUC0-τ] either every 3 weeks [AUC0-21 days] or every 4 weeks [AUC0-28 days]) and maximum concentration in a dosing interval (Cmax) in participants diagnosed with primary humoral immunodeficiency (PI) currently receiving chronic IVIG replacement treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 28, 2022
• Est. primary completion date: March 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female between 18 and 75 years of age (inclusive) at Screening

• Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring IV 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 [IgM] immunodeficiency syndrome).

• IgG trough level =500 milligrams per deciliter (mg/dL) at screening visit. Note:

Patients entering Group 1 must additionally have trough levels =500 mg/dL documented within the previous year. For patients entering Group 2, if Screening trough levels are not =500 mg/dL, the subject will be a Screen Failure, but may be rescreened following dose adjustment of their original IV IgG replacement therapy regimen and recording an IgG trough level =500 mg/dL

• Has not had an SBI within the last 6 months prior to screening or during the screening.

• Medical records are available to document diagnosis, previous infections, and treatment.

• Willing to comply with all aspects of the study protocol, including blood sampling, for the duration of the study.

• Signed and dated a written informed consent form (ICF) confirming his or her willingness to participate in study GC1902.

Exclusion Criteria:

• Has 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 1000per microliters (1000/µL) [1.0 x 10^9/L]), or human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS).

• Has known selective Immunoglobulin A (IgA) deficiency (with or without antibodies to IgA). (Note: exclusion is for the specific diagnostic entity. It does not exclude other forms of primary humoral immunodeficiency which have decreased IgA in addition to decreased IgG requiring IgG replacement).

• Has isolated IgG subclass deficiency or an isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy

• The subject has had a known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product.

• Has a history of thrombotic complications following IVIG therapy.

• Has a history of or current diagnosis of deep venous thrombosis (DVT) or thromboembolism (e.g., myocardial infarction, cerebrovascular accident or transient ischemic attack); history refers to an incident in the year prior to the Screening Visit or 2 episodes over lifetime or has thrombosis risk factors (e.g., prolonged immobilization, use of estrogens, indwelling central vascular catheters).

• Has a known hyperviscosity syndrome or hypercoagulable states.

• Has liver enzyme levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gammaglutamyl transferase [GGT], or lactate dehydrogenase [LDH]) greater than 2.5 times the upper limit of normal (ULN) at the screening visit as defined by the testing laboratory.

• Has pre-existing renal impairment (defined by serum creatinine greater than 1.5 times the ULN or blood urea nitrogen [BUN] greater than 2.5 times the ULN, or any subject who is on dialysis) at the screening visit or any history of acute renal injury.

• Has clinically significant history of drug or alcohol abuse or dependence in the opinion of the Investigator (must be within the past 12 months and noted in the subject's medical records or documented at screening).

• Clinical evidence of any significant acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the Investigator, may interfere with the conduct of the study or may place the subject at undue medical risk.

• Females of childbearing potential who are pregnant, have a positive pregnancy test at Screening (human chorionic gonadotropin [HCG]-based assay), are breastfeeding, or unwilling to practice a highly effective method of contraception (eg, oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study. Note: True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception).

• 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 not exceeding >1mg of prednisone equivalent/kg/day for >30 days would not exclude the subject. Inhaled or topical corticosteroids are allowed.

• Has uncontrolled arterial hypertension (systolic blood pressure [SBP] >160 mm Hg and/or diastolic blood pressure [DBP] >100 mm Hg)

• Has hemoglobin <11 g/dL at the Screening Visit

• Unable or unwilling to provide a storage serum sample at the Screening Visit. Note: A pre-treatment serum sample to be stored at -94°F (-70ºC) for possible future testing is required.

• Received any live virus vaccine within 5 months prior to the Screening Visit and not willing to postpone receiving any live virus vaccines until 6 months after completing study treatment

• Has a known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

• Has participated in another clinical trial within 30 days prior to Screening or has received any investigational product, with the exception of other IgG products, within the previous 3 months prior to the Screening Visit

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency
• Primary Immunodeficiency Diseases

Intervention

Biological:
• Gamunex-C
Intravenous infusion.
• IVIG-PEG
Intravenous infusion.

Locations

Country	Name	City	State
United States	Alabama Allergy & Asthma Center	Birmingham	Alabama
United States	Institute for Asthma and Allergy	Chevy Chase	Maryland
United States	Optimed Research, LLC	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Allergy Partners of North Texas Research	Dallas	Texas
United States	Allergy, Asthma & Immunology Clinic, P.A.	Irving	Texas
United States	Allergy Associates of the Palm Beaches PA	North Palm Beach	Florida
United States	Washington University	Saint Louis	Missouri
United States	The South Bend Clinic Center for Research	South Bend	Indiana
United States	Allergy, Asthma and Immunology Center, P.C.	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC (0-7): Area Under the Concentration Time Curve Over a Dosing Interval of Either Every 3 Weeks [AUC0-21 Days] or Every 4 Weeks [AUC0-28 Days] for Total Immunoglobulin G (IgG)	AUC (0-7 days) is calculated as AUC (0-21 days)/3 for subjects with a dosing frequency of every 3 weeks and as AUC(0-28 days)/4 for subjects with a dosing frequency of every 4 weeks.	Pre-dose, within 10 minutes of last infusion completion, at 1, 3, 6, 24, 48 hours and 4, 7, 14 and 21 days (up to 3 weeks), and 28 days (up to 4 weeks - only for subjects on a 4-week dosing schedule) post-infusion
Primary	Cmax: Maximum Concentration in a Dosing Interval for Total IgG		Pre-dose, within 10 minutes of last infusion completion, at 1, 3, 6, 24, 48 hours, and 4, 7, 14, 21 and 28 days post-infusion (up to 4 weeks)
Secondary	Rate of Serious Bacterial Infections (SBIs)	The rate of SBI events per participant per year during treatment was calculated as the total number of SBI events divided by the total duration of exposure in years across all participants. The 2-sided 98% confidence interval (CI) was determined from a generalized linear model for Poisson regression for the log-transformed number of events with log-transformed duration of exposure in years as an offset variable.	Baseline up to 6 months for each period, i.e., overall GC treatment phase and overall IVIG-PEG treatment phase with an aggregate duration of up to 12 months
Secondary	Rate of Events Per Participant Per Year in Participants With Any Kind of Infection	Rate of events per participant per year is calculated as the total number of events divided by the total duration of exposure in years across all participants. Any kind of infections included serious/nonserious including acute sinusitis, exacerbation of chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea etc.) as determined by the Investigator.	Baseline up to 6 months for each period, i.e., overall GC treatment phase and overall IVIG-PEG treatment phase with an aggregate duration of up to 12 months
Secondary	Rate of Days Per Person Per Year That Participants Were on Antibiotics	Rate of days per person per year is calculated as the total number of days divided by the total duration of exposure in years across all participants. Antibiotics included prophylactic and therapeutic.	Baseline up to 6 months for each period, i.e., overall GC treatment phase and overall IVIG-PEG treatment phase with an aggregate duration of up to 12 months
Secondary	Number of Participants Hospitalized Due to Infection	Hospitalization was considered only in cases of hospital admission (including emergency room stay) for equal or more than 24 hours.	Baseline up to 6 months for each period, i.e., overall GC treatment phase and overall IVIG-PEG treatment phase with an aggregate duration of up to 12 months
Secondary	Rate of Days of Work/School/Daily Activities Missed Per Participant Due to Infections and Their Treatment	Rate of days per person per year is calculated as the total number of days divided by the total duration of exposure in years across all participants.	Baseline up to 6 months for each period, i.e., overall GC treatment phase and overall IVIG-PEG treatment phase with an aggregate duration of up to 12 months