Clinical trial NCT03054181: Facilitated Immunoglobulin Administration Registry and Outcomes Study (FIGARO)
Official title: Facilitated Immunoglobulin Administration Registry and Outcomes Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Immunodeficiency
Secondary Immune Deficiency
Keywords: Observational
Infection
Utilisation
Safety
Tolerability
Infusion
chronic
Lead sponsor: GWT-TUD GmbH
Sponsor class: OTHER
First posted: 2017-02-15
Enrollment: 156
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary (PID) or secondary immunodeficiencies (SID)

Brief summary: Long-term observational study on the utilisation and outcomes of HyQvia (a product consisting of recombinant human hyaluronidase and a human normal immunoglobulin 10% solution) under everyday clinical practice conditions.

Detailed description: Recombinant hyaluronidase is an established therapeutic principle to facilitate the infusion of large volumes of fluids subcutaneously (e.g. Ringer solution and antibodies such as IG, rituximab, trastuzumab).

HyQvia is a product consisting of recombinant human hyaluronidase (rHuPH20, Hylenex®), and a human normal immunoglobulin (IG). The subcutaneous (SC) IG is a 10% solution prepared from human plasma consisting of at least 98% immunoglobulin G, which contains a broad spectrum of antibodies.

The two components are packaged together as a dual vial unit: IG provides the therapeutic effect and the recombinant human hyaluronidase facilitates the dispersion, which alters the kinetics of absorption and increases the bioavailability of the IG.

HyQvia is marketed in the European Union (EU) since July 2013 and in the USA since September 2014. In the EU, HyQvia is indicated as replacement therapy in patients of all age groups in primary immunodeficiency syndromes (PID), and in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections (secondary immunodeficiency syndromes, SID), as well as hypogammaglobulinaemia and pre- and post-allogeneic hematopoietic stem cell transplantation.

HyQvia was investigated in one pivotal study lasting over a year, involving 89 patients with PID who had already had treatment with human normal IG for at least three months. The number of acute serious bacterial infections (SBI) as main efficacy outcomes was 0.025 per year. This was below the FDA predefined number needed to show efficacy (SBI rate \<1.0 per subject per year at the 0.01 level of significance), and was similar to that seen with other licensed human normal IG products. In the pivotal study and its extension, 188 patient years under HyQvia treatment have been documented. HyQvia was efficacious, safe, and bioequivalent to intravenous IG at the same administration intervals, but it caused fewer systemic reactions. Tolerability was good despite high infusion volumes and rates. There are no preclinical data that suggest an increased risk of mutagenicity, teratogenicity, fertility or neuronal development.

The most current and comprehensive data on real-life utilisation and outcomes of various IgG preparations is available from the German SIGNS registry. This registry confirmed the effectiveness of IgG substitution or treatment in terms of reduction of infections (PID and SID), as well as stabilization or improvement of the clinical condition in neurological and autoimmune diseases. In a cohort of 24 PID and SID patients on HyQvia in the German SIGNS study, the preparation was well tolerated and treatment satisfaction was high. In other countries, data on the utilisation and outcomes of HyQvia under clinical practice conditions are sparse or completely missing.

The present study aims to fill these gaps and to provide a detailed and complete description of the utilisation of under everyday clinical practice conditions.

Eligibility criteria: Inclusion Criteria:

* Patient has received/will receive at least 1 HyQvia infusion for PID or SID
* Patient has an indication for chronic immunoglobulin treatment
* Patient is likely available for long-term documentation
* Patient provides informed consent for documentation

Exclusion Criteria:

* No explicit exclusion criteria apply.

Primary outcomes:
measure: Utilisation in terms of dose and dosing interval
timeFrame: up to 3 years
Secondary outcomes:
measure: Adverse events
timeFrame: up to 3 years
measure: Concomitant diseases
timeFrame: up to 3 years
measure: mean immunoglobulin trough level
timeFrame: up to 3 years
measure: Number of participants with treatment-related adverse events
timeFrame: up to 3 years
measure: Number of training session
timeFrame: up to 3 years
measure: Number of days in hospital
timeFrame: up to 3 years
measure: Number of days in rehabilitation clinic
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Paris
country: France
facility: University Hospital
city: Berlin
country: Germany
facility: Charité
city: Leipzig
country: Germany
facility: Hospital for Children and Adolescents, St. Georg Hospital, Academic Teaching Hospital
city: Roma
country: Italy
facility: La Sapienza University
Study officials:
affiliation: Fachbereich Pädiatrische Rheumatologie, Immunologie und Infektiologie am Klinikum St. Georg Leipzig
name: Michael Borte, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: GWT-TUD GmbH, Dresden, Germany
name: David Pittrow, MD
role: STUDY_DIRECTOR
affiliation: Sapienza University Rome, Italy
name: Isabelle Quinti, MD
role: STUDY_CHAIR
affiliation: Charité Berlin, Germany
name: Leif Hanitsch, MD
role: STUDY_CHAIR
affiliation: University Hospital, Paris, France
name: Nizar Mahlaoui, MD
role: STUDY_CHAIR
References:
citation: Borte M, Hanitsch LG, Mahlaoui N, Fasshauer M, Huscher D, Speletas M, Dimou M, Kamieniak M, Hermann C, Pittrow D, Milito C. Facilitated Subcutaneous Immunoglobulin Treatment in Patients with Immunodeficiencies: the FIGARO Study. J Clin Immunol. 2023 Aug;43(6):1259-1271. doi: 10.1007/s10875-023-01470-2. Epub 2023 Apr 10.