Efficacy, Pharmacokinetics, Safety, and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency

NCT02806986 | Completed Phase 3 Results

• 2 other identifiers: GTI15032015-003290-15
• Study Type: interventional
• Target: 61
• Locations: 9 countries
• Sites: 23

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.

Conditions

Primary Immunodeficiency

Outcome Measures

Primary Outcomes (1)

• Rate of Serious Bacterial Infection (SBI) Per Participant Per Year

  The rate of SBI events per participant per year during IGSC 20% 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.

  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 (5)

• Mean Trough Total IgG Concentration

  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

• Rate of Infection of Any Kind Per Participant Per Year

  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

• Rate of Days on Antibiotics Per Participants Per Year

  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

• Rate of Hospitalization Due to Infection Per Participants Per Year

  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

• Rate of Days of Work/School/Daily Activities Missed Per Participants Per Year Due to Infections and Related Treatment

  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

Study Arms (1)

IGSC 20%

EXPERIMENTAL

13 doses of IGSC 20% in Treatment Stage 1 and 39 doses of IGSC 20% in Treatment Stage 2 for a total of 52 doses if IGSC 20%

Biological: IGSC 20%

Interventions

IGSC 20% BIOLOGICAL

Weekly administration of IGSC 20% via intravenous infusion

Also known as: Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography

IGSC 20%

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (23)

Wesley Medical Research

Auchenflower, 4066, Australia

Location

Royal Melbourne Hospital

Parkville, 3050, Australia

Location

University Hospital

Hradec Králové, 50005, Czechia

Location

CHU de Montpellier

Montpellier, 34295, France

Location

Klinikum Dortmund gGmbH

Dortmund, 44137, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Children's Hospital at Municipal Hospital St. Georg

Leipzig, 04129, Germany

Location

University Hospital of Mainz

Mainz, 55131, Germany

Location

Asklepios Klinik Sankt Augustin

Sankt Augustin, 53757, Germany

Location

United St Istvan and St Laszlo Hospital

Budapest, Hungary

Location

Josa Andras County Hospital

Nyiregyháza, H-4400, Hungary

Location

The Children's Memorial Health Institute

Warsaw, 4736, Poland

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08025, Spain

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital Universitari Sant Joan de Déu

Barcelona, 08950, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 Octubre

Madrid, 28041, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

Stockholm

Stockholm, SE-14186, Sweden

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

St Bartholomew's Hospital

London, E1 2ES, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins; Caprylates; Chromatography

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Rhonda Griffin
• Organization: Grifols Therapeutics LLC

rhonda.griffin@grifols.com

919-316-6693

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 21, 2016
• Study Start: June 1, 2016
• Primary Completion: May 15, 2019
• Study Completion: May 15, 2019
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); AU (2); CZ (1); DE (5); HU (2); ES (7); SE (1); FR (1); PL (1)