Facilitated Immunoglobulin Administration Registry and Outcomes Study (FIGARO) (FIGARO)

Facilitated Immunoglobulin Administration Registry and Outcomes Study

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.

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency; Secondary Immune Deficiency
• Intervention / Treatment: Biological: HyQvia

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.

• Study Type: Observational
• Enrollment (Actual): 156

Contacts and Locations

Study Locations

• France
  • Paris, France
    • University Hospital
• Germany
  • Berlin, Germany
    • Charité
  • Leipzig, Germany
    • Hospital for Children and Adolescents, St. Georg Hospital, Academic Teaching Hospital
• Italy
  • Roma, Italy
    • La Sapienza University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary (PID) or secondary immunodeficiencies (SID)

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HyQvia; Recombinant human hyaluronidase and normal immunoglobulin 10%	Biological: HyQvia; Other Names: Recombinant human hyaluronidase and normal immunoglobulin 10%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utilisation in terms of dose and dosing interval	mean monthly dose	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence and type	up to 3 years
Concomitant diseases		up to 3 years
mean immunoglobulin trough level	after HyQvia infusion	up to 3 years
Number of participants with treatment-related adverse events	Acute bacterial infections; overall infections	up to 3 years
Number of training session	about appropriate self-infusion	up to 3 years
Number of days in hospital		up to 3 years
Number of days in rehabilitation clinic		up to 3 years

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Investigators: Principal Investigator: Michael Borte, MD, PhD, Fachbereich Pädiatrische Rheumatologie, Immunologie und Infektiologie am Klinikum St. Georg Leipzig; Study Director: David Pittrow, MD, GWT-TUD GmbH, Dresden, Germany; Study Chair: Isabelle Quinti, MD, Sapienza University Rome, Italy; Study Chair: Leif Hanitsch, MD, Charité Berlin, Germany; Study Chair: Nizar Mahlaoui, MD, University Hospital, Paris, France

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: February 13, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Safety; Infection; Observational; chronic; Tolerability; Infusion; Utilisation
• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins
• Other Study ID Numbers: FIGARO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No