Clinical trial NCT02806986: Efficacy, Pharmacokinetics, Safety, and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
Official title: A Multi-Center, Open-Label, Single-Arm Trial to Evaluate Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2016-06-21
Enrollment: 61
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) who complete the entire study. This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses). A total of 52 doses of IGSC 20% will be administered with a final follow-up visit 1 week after the last dose at Week 53. Subjects/caregivers will be trained on self-administration of IGSC 20% by the clinical site personnel.

Detailed description: This is a prospective, multi-center, open-label, single-arm, efficacy, PK, safety and tolerability study of IGSC 20% in subjects with PI. Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered IGSC 20% who complete the entire study.

This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses).

Previous Regimen Phase: Subjects will be infused with their current ongoing ("previous regimen") intravenous immune globulin/subcutaneous immune globulin (IVIG/SCIG) regimen (pIV/pSC) in the clinic to obtain 2 trough immunoglobulin G (IgG) levels (obtained prior to each pIV/pSC infusion) on each subject's "previous regimen".

20% IGSC Treatment Stage 1: The first dose of IGSC 20% will be administered at the clinical site immediately after Baseline assessments are complete (SC#1). All subjects will receive 13 IGSC 20% infusions at weekly intervals. IgG trough blood levels will be measured at all (except SC#3) study visits All other doses of IGSC 20% may be infused at home (once properly trained) or in the clinic. The Treatment Stage 1 dose will continue into IGSC 20% Treatment Stage 2.

IGSC 20% Treatment Stage 2: The IGSC 20% dose (mg/kg) will remain constant with no dose adjustment permitted in this phase, unless it is absolutely medically necessary. While all subjects will have a SC#17 clinic visit and standard assessments, serial pharmacokinetics (PK) sampling will only be performed in a subset of adult subjects:

Eligibility criteria: Inclusion Criteria:

* Pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring IgG replacement therapy
* No serious bacterial infection within the 3 months prior to Screening and has no serious bacterial infections (SBIs) up to the time of the Baseline Visit
* Currently on IgG replacement therapy (stable regimen \[dose and dosing interval\] via IV or SC infusion) for ≥ 3 consecutive months at a dosage of at least 200 mg/kg per infusion
* Documented (within previous 3 months) of an IgG trough level of ≥ 500 mg/dL on current IgG replacement therapy regimen
* Screening/pre-Baseline trough IgG levels must be ≥ 500 mg/dL.

Exclusion Criteria:

* Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
* 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
* Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
* Nephrotic syndrome, and/or a history of acute renal failure, and/or severe renal impairment, and/or is on dialysis
* Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
* History of (year prior to Screening or 2 episodes in lifetime) or current diagnosis of deep venous thrombosis or thromboembolism (e.g., myocardial infarction, cerebrovascular accident, or transient ischemic attack)
* Acquired medical condition 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
* HIV positive by nucleic acid amplification technology based on a Screening blood sample
* Uncontrolled arterial hypertension (adult subjects: systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg)
* 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.

Primary outcomes:
measure: Rate of Serious Bacterial Infection (SBI) Per Participant Per Year
timeFrame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Secondary outcomes:
measure: Mean Trough Total IgG Concentration
timeFrame: Previous Regimen Phase: 2 timepoints pre-dose of pIV or pSC between Screening and Baseline (up to 8 weeks). IGSC 20% Phase: Pre-dose of IGSC 20% at Baseline (Week 1), Weeks 2, 5, 9, 13, 17, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Week 53
measure: Rate of Infection of Any Kind Per Participant Per Year
timeFrame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
measure: Rate of Days on Antibiotics Per Participants Per Year
timeFrame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
measure: Rate of Hospitalization Due to Infection Per Participants Per Year
timeFrame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
measure: Rate of Days of Work/School/Daily Activities Missed Per Participants Per Year Due to Infections and Related Treatment
timeFrame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Other outcomes:
Locations:
city: Auchenflower
country: Australia
facility: Wesley Medical Research
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Hradec Kralove
country: Czechia
facility: University Hospital
city: Montpellier
country: France
facility: CHU de Montpellier
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Leipzig
country: Germany
facility: Children's Hospital at Municipal Hospital St. Georg
city: Mainz
country: Germany
facility: University Hospital of Mainz
city: Sankt Augustin
country: Germany
facility: Asklepios Klinik Sankt Augustin
city: Budapest
country: Hungary
facility: United St Istvan and St Laszlo Hospital
city: Nyiregyháza
country: Hungary
facility: Josa Andras County Hospital
city: Warsaw
country: Poland
facility: The Children's Memorial Health Institute
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Sant Joan de Déu
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 Octubre
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Stockholm
country: Sweden
facility: Stockholm
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
References: