Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial. (9th February 2021)

• Record Type: Journal Article
• Authors: Bril, Vera; Benatar, Michael; Andersen, Henning; Vissing, John; Brock, Melissa; Greve, Bernhard; Kiessling, Peter; Woltering, Franz; Griffin, Laura; Van den Bergh, Peter
• Other Names: Benarik Josef author non-byline.; Beydoun Said author non-byline.; Blaes Franz author non-byline.; De Bleecker Jan author non-byline.; Freimer Miriam author non-byline.; Genge Angela author non-byline.; Grosskreutz Julian author non-byline.; Guerrero Sola Antonio author non-byline.; Guptill Jeffrey author non-byline.; Sendra Isabel Illa author non-byline.; Jander Sebastian author non-byline.; Junkerova Jana author non-byline.; Mozaffar Tahseen author non-byline.; Nicolle Michael author non-byline.; Rivner Michael author non-byline.; Van Damme Philip author non-byline.; Vu Tuan author non-byline.; Tackenberg Björn author non-byline.; Thomsen Jan author non-byline.; Vohanka Stanislav author non-byline.; Horakova Magda author non-byline.; Horak Thomas author non-byline.; Granit Volkan author non-byline.; Lin Frank author non-byline.; Rad Nazila author non-byline.; Parker John author non-byline.; Souza Andrezza author non-byline.; Schultheiss Thorsten author non-byline.; Bindler Christine author non-byline.; Katzberg Hans author non-byline.; Cardoen Stefanie author non-byline.; Arnold William author non-byline.; Kissel John author non-byline.; Elsheikh Bakri author non-byline.; Hoyle Joseph author non-byline.; Massie Rami author non-byline.; Dong Xin author non-byline.; Smesny Uta author non-byline.; Roediger Annekathrin author non-byline.; Ilse Benjamin author non-byline.; Gunkel Anne author non-byline.; Radscheidt Monique author non-byline.; Horga Alejandro author non-byline.; Galán Lucía author non-byline.; Juel Vern author non-byline.; Rojas Garcia Ricardo author non-byline.; Cortés Vincente Elena author non-byline.; Querol Gutiérrez Luis author non-byline.; Gliem Michael author non-byline.; Lee John-Ih author non-byline.; Reguliova Katarina author non-byline.; Kuchar Marian author non-byline.; Goyal Namita author non-byline.; FlorendoCumbermack Anita author non-byline.; Hartmann John author non-byline.; Manghram Diane author non-byline.; Eienbröker Christian author non-byline.; Vandenbussche Nicolas author non-byline.; Vynckier Jan author non-byline.; Claeys Kristl author non-byline.; Van Daele Sien author non-byline.; Sanders Katrien author non-byline.; Dobbels Laurens author non-byline.; Van Parijs Vinciane author non-byline.; Witting Nanna author non-byline.; Højgaard Joan Lilja author non-byline.; Farias Jerrica author non-byline.; Suresh Niraja author non-byline.;
• Is Part Of: Neurology. Volume 96:Number 6(2021)
• Page Start: e853
• Page End: e865
• Publication Date: 2021-02-09
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000011108
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG). Methods: In this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1–29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29–43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44–99). Primary endpoint was change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints were change from baseline to day 29 in MG–Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores and safety. Results: Forty-three patients were randomized (rozanolixizumab 21, placebo 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo was as follows: QMG (LS mean −1.8 vs −1.2, difference −0.7, 95% upper confidence limit [UCL] 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean −1.8 vs −0.4, difference −1.4, 95% UCL −0.4), and MGC (LS mean −3.1 vs −1.2, difference −1.8, 95% UCL 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab 57%, placebo 14%). Conclusion: Whereas change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422). Classification of Evidence: This study provides Class I evidence that for patients with gMG, rozanolixizumab is well-tolerated, but did not significantly improve QMG score.