eprintid: 10204836
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/20/48/36
datestamp: 2025-02-18 12:06:15
lastmod: 2025-02-18 12:06:15
status_changed: 2025-02-18 12:06:15
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Denton, Christopher P
creators_name: Kowal-Bielecka, Otylia
creators_name: Proudman, Susanna M
creators_name: Olesińska, Marzena
creators_name: Worm, Margitta
creators_name: Del Papa, Nicoletta
creators_name: Matucci-Cerinic, Marco
creators_name: Radewonuk, Jana
creators_name: Jochems, Jeanine
creators_name: Panaite, Adrian
creators_name: Shebl, Amgad
creators_name: Krupa, Anna
creators_name: Allanore, Yannick
creators_name: Hofmann, Jutta H
creators_name: Gasior, Maria J
title: A Phase 2 randomised trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G90
keywords: Pharmacokinetics, subcutaneous immunoglobulin, intravenous immunoglobulin, systemic sclerosis
note: © The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
abstract: OBJECTIVES: The primary objective was the safety of subcutaneous immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with diffuse cutaneous systemic sclerosis (dcSSc). Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of intravenous immunoglobulin, IgPro10 (Privigen, CSL Behring). METHODS: In this prospective, multicentre, randomised, open-label, crossover Phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over 2–5 sessions), or vice-versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed. RESULTS: Twenty-seven patients were randomised from 9 October 2019–31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced ten SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum immunoglobulin G concentration (mean [standard deviation]) was numerically lower following IgPro20 (23.7 [1.2] g/l) vs IgPro10 (46.1 [1.2] g/l), as was the geometric mean dose-normalised, baseline-corrected area under the concentration-time curve from time point 0 to tau (IgPro20, 44.8 [1.4] h*g/l; IgPro10, 60.2 [1.4] h*g/l). The bioavailability of IgPro20 relative to IgPro10 was 76.1%. CONCLUSION: This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.
date: 2025-02-05
date_type: published
publisher: Oxford University Press (OUP)
official_url: https://doi.org/10.1093/rheumatology/keaf066
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2359993
doi: 10.1093/rheumatology/keaf066
lyricists_name: Denton, Christopher
lyricists_id: CPDEN87
actors_name: Denton, Christopher
actors_id: CPDEN87
actors_role: owner
full_text_status: public
publication: Rheumatology
citation:        Denton, Christopher P;    Kowal-Bielecka, Otylia;    Proudman, Susanna M;    Olesińska, Marzena;    Worm, Margitta;    Del Papa, Nicoletta;    Matucci-Cerinic, Marco;                                 ... Gasior, Maria J; + view all <#>        Denton, Christopher P;  Kowal-Bielecka, Otylia;  Proudman, Susanna M;  Olesińska, Marzena;  Worm, Margitta;  Del Papa, Nicoletta;  Matucci-Cerinic, Marco;  Radewonuk, Jana;  Jochems, Jeanine;  Panaite, Adrian;  Shebl, Amgad;  Krupa, Anna;  Allanore, Yannick;  Hofmann, Jutta H;  Gasior, Maria J;   - view fewer <#>    (2025)    A Phase 2 randomised trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis.                   Rheumatology        10.1093/rheumatology/keaf066 <https://doi.org/10.1093/rheumatology%2Fkeaf066>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10204836/1/Denton%20et%20al_SSc%20MS_Rheumatology_Manuscript_for%20UCL%20upload.pdf