Study Evaluating IGSC 20% Flexible Dosing in Treatment-Experienced and Treatment-Naive Subjects With Primary Immunodeficiency

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03814798
• Date of registration: 22/01/2019
• Prospective Registration: Yes
• Primary sponsor: Grifols Therapeutics LLC
• Public title: Study Evaluating IGSC 20% Flexible Dosing in Treatment-Experienced and Treatment-Naive Subjects With Primary Immunodeficiency
• Scientific title: A Multicenter, Randomized, Cross-over, Open-label Study to Evaluate IGSC 20% Flexible Dosing Including Daily Push Dosing In Treatment-Experienced Subjects With Primary Immunodeficiency (PI) and Evaluation of Loading/Maintenance IGSC 20% in Treatment-Naïve Subjects With PI
• Date of first enrolment: December 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03814798
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

For treatment-experienced subjects:

- Has documented and confirmed pre-existing diagnosis of PI with features of
hypogammaglobulinemia requiring IgG replacement therapy including but not limited to
the following humoral-based immunodeficiency syndromes (eg, X-linked
agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency
syndromes without lymphocytopenia (eg, hyper immunoglobulin M immunodeficiency
syndrome).

- Has not had a SBI or been hospitalized for infection of any etiology (eg, viral,
fungal, parasitic) within the last 3 months prior to screening or during screening.

- Is currently receiving IgG replacement therapy for =3 months via IV or SC infusion.
Subjects receiving IVIG prior to study must receive a dosage of at least 200 mg/kg per
infusion

- Has Screening IgG trough levels =500 mg/dL. Note: If screening trough levels are not
above this threshold, the subjects will be considered a screen failure, but may be
rescreened following dose adjustment of their original IgG replacement therapy regimen
and maintaining stable dosing for a period of at least 3 months prior to screening a
second time.

- Has signed an informed consent. Note: The subject must sign the informed consent form
(ICF) if at least 18 years old; for children of younger age, the subject's parent or
legal guardian must sign the ICF and if appropriate/applicable, the subject must sign
a Child Assent form approved by the IRB/EC per the institution's requirements

For treatment-naïve subjects:

- Has 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 (eg, X-linked agammaglobulinemia, common
variable immunodeficiency), and combined immunodeficiency syndromes without
lymphocytopenia (eg, hyper immunoglobulin M immunodeficiency syndrome).

- Has never received IgG replacement treatment (ie, no prior immune globulin replacement
therapy)

- Has Screening IgG level =400 mg/dL

- Does not have an SBI nor requires hospitalization for infection of any etiology (eg,
viral, fungal, parasitic) during screening or at baseline.

- Has signed an informed consent. Note: The subject must sign the informed consent form
(ICF) if at least 18 years old; for children of younger age, the subject's parent or
legal guardian must sign the ICF and if appropriate/applicable, the subject must sign
a Child Assent form approved by the IRB/EC per the institution's requirements

Exclusion Criteria:

For all subjects:

- Has 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.

- Has had a known serious adverse reaction to immunoglobulin or any anaphylactic
reaction to blood or any blood-derived product

- Has 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.

- Has known isolated IgG subclass deficiency; isolated specific antibody deficiency
(SAD) or selective IgG deficiency; or transient hypogammaglobulinemia of infancy.
Note: Subjects are not to be enrolled if their primary PI diagnosis does not entail an
actual quantitative deficit in total IgG. For example, SAD is defined as an impaired
specific IgG response to pneumococcal vaccine with normal serum concentrations of IgG,
IgM, and IgA. Isolated IgG subclass deficiency is defined as an abnormally low level
of 1 or more IgG subclass in subjects with normal levels of total IgG and IgM.

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

- Is female of childbearing potential who is pregnant, has a positive pregnancy test at
screening (serum human chorionic gonadotropin [HCG]- based assay), is breastfeeding,
or is unwilling to practice a highly effective method of contraception (oral,
injectable or implanted hormonal methods of contraception, placement of an
intrauterine device or intrauterine system, 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 [eg, calendar, ovulation,
symptothermal, post-ovulation methods], declaration of abstinence for the duration of
a trial, and withdrawal are not acceptable methods of contraception.)

- Has significant proteinuria (=3+ or known urinary protein loss >1 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 or creatinine more
than 2.5 times the upper limit of normal [ULN]).

- Has 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.

- Has hemoglobin <9 g/dL at screening.

- Has 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 (eg,
myocardial infarction, cerebrovascular accident or transient ischemic attack) or deep
venous thrombosis.

- Is currently receiving anti-coagulation therapy which would make SC administration
inadvisable (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [eg,
dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban
targeting Factor Xa], and parenteral anticoagulants [eg, fondaparinux]).

- Currently has a known hyperviscosity syndrome.

- 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 1000/µL [1.0 x 10^9/L]), or human
immunodeficiency virus infection/acquired immune deficiency syndrome.

- Has a known previous infection with or clinical signs and symptoms consisten


Age minimum: 2 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency

Intervention(s)

Biological: IGSC 20% daily push versus every 2 weeks pump

Biological: IGSC 20% daily push versus 2 times per week pump

Biological: IGSC 20% 150 mg/kg

Biological: IGSC 20% daily push versus once a week pump

Primary Outcome(s)

Steady-state mean trough (predose) concentration of total IgG [Time Frame: Baseline to Week 32]

Secondary ID(s)

GC1701

Source(s) of Monetary Support

Please refer to primary and secondary sponsors