Evaluation of shorter infusion times for Ocrelizumab treatment in an extension substudy of the phase IIIb CHORDS trial
ECTRIMS Online Library. Bermel R. 09/13/19; 278608; P1408
Robert Bermel
Robert Bermel
Contributions
Abstract

Abstract: P1408

Type: Poster Sessions

Abstract Category: Therapy - Risk management for disease modifying treatments

R. Bermel1, E. Waubant2, G. Pardo3, A. Bass4, P. Repovic5, S. Newsome6, J.W. Lindsey7, X. Ma8, A. Pradhan8, B. Musch8, A. Zabeti9

1Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, 2University of California, San Francisco, San Francisco, CA, 3Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Neurology Center of San Antonio, San Antonio, TX, 5Swedish Neuroscience Institute, Seattle, WA, 6Johns Hopkins Hospital, Baltimore, MD, 7UT Physicians Neurology-Texas Medical Center, Houston, TX, 8Genentech, Inc., South San Francisco, CA, 9UC Waddell Center for Multiple Sclerosis, Cincinnati, OH, United States

Background: Ocrelizumab (OCR) is a CD20-directed humanised monoclonal antibody approved for the treatment of relapsing and primary progressive multiple sclerosis (MS). The US prescribing information (USPI) for OCR recommends that patients initially complete two 300-mg infusions administered over 2.5 h, followed by single 600-mg infusions administered over 3.5 h. Reduced infusion time may improve the patient experience and optimise resource utilisation for healthcare practices.
Objectives: To report the safety of shorter OCR infusions from the Phase IIIb CHORDS (NCT02637856) extension substudy.
Methods: In the single-arm open-label CHORDS study, patients aged 18 to 55 y with relapsing-remitting MS and a suboptimal response to a previous disease-modifying treatment received two 300-mg OCR infusions separated by 2 wk, followed by 600-mg infusions every 24 wk; infusions were administered at the USPI-approved rate. Patients who tolerated OCR well up to Wk 72 (Dose 4) were eligible for an optional substudy at Wk 96 in which OCR 600 mg (Dose 5) was infused over 2 h. The primary endpoint of the substudy is the frequency of NCI CTCAE v4.0 Grade 3 and 4 infusion-related reactions (IRRs) after the shorter Wk 96 infusion; secondary endpoints include changes in physical findings and vital signs at Wk 96 and at a 30-day follow-up visit.
Results: As of 29 January 2019, 129 patients were enrolled in the substudy and all had completed the shorter infusion; 121 patients (93.8%) completed the shorter infusion in ≤2.5 h. Adverse events on the same day as the shorter infusion were reported in 19 patients (14.7%), including 16 (12.4%) with IRRs. No Grade 3/4 or serious IRRs were observed; 10 (7.8%) and 6 (4.7%) patients experienced Grade 1 and 2 IRRs, respectively. In comparison, 54 of 567 patients (9.5%) reported IRRs with the Wk 72 infusion (Dose 4) in the main CHORDS study in which OCR was infused over 3.5 h per USPI recommendations. Outcomes associated with the primary endpoint and other safety findings from the full population through the 30-d follow-up period will be presented.
Conclusions: These findings provide information on the safety of shorter OCR infusions. Specifically, in this substudy of CHORDS patients who completed and tolerated 4 doses of OCR per USPI recommendations, administration of OCR Dose 5 (600 mg) over a reduced infusion time of 2 h was not associated with an increased risk of serious, severe or life-threatening IRRs.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance were provided by Health Interactions, USA.
R. Bermel has received consulting fees from Biogen, F. Hoffmann-La Roche Ltd and Genentech, Inc., Genzyme and Novartis.
E. Waubant is site PI for ongoing trials with Genentech, Inc. and Biogen. She has research funding from NIH, PCORI, NMSS, and Race to Erase MS. She has received honoraria for lectures for Medscape, The Corpus and AAN, and for consulting work from Jazz Pharmaceuticals, Emerald and DBV. She is co-chief editor for MSARD.
G. Pardo has received personal compensation for consulting and/or speakers bureau from Biogen, Celgene, EMD Serono, Genentech, Inc., Novartis, Sanofi and Teva.
A. Bass has served on advisory boards and/or speaker bureaus and received research funding for Actelion, Biogen, EMD Serono, Genentech-Roche, Mallinckrodt, Novartis, Sanofi-Genzyme and TG Therapeutics.
P. Repovic has received consulting or speaking honoraria from Acorda, Alexion, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva
S. Newsome has been a consultant/advisor for Biogen, Genentech, Inc., Celgene, EMD Serono, Gerson Lehrman Group, Clinical Adjudication Committee Member for a medDay Pharmaceuticals clinical trial and has received research funding (paid directly to Institution) from Biogen, Genentech, Inc., Department of Defense, National MS Society, Patient-Centered Outcomes Research Institute.
J. Lindsey has nothing to disclose.
X. Ma is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
A. Pradhan is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
B. Musch is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
A. Zabeti received honoraria for speaker's bureau or advisory councils from ACORDA, BIOGEN, Celgene, Genentech, Genzyme/Sanofi, Novartis and Serono.

Abstract: P1408

Type: Poster Sessions

Abstract Category: Therapy - Risk management for disease modifying treatments

R. Bermel1, E. Waubant2, G. Pardo3, A. Bass4, P. Repovic5, S. Newsome6, J.W. Lindsey7, X. Ma8, A. Pradhan8, B. Musch8, A. Zabeti9

1Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, 2University of California, San Francisco, San Francisco, CA, 3Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Neurology Center of San Antonio, San Antonio, TX, 5Swedish Neuroscience Institute, Seattle, WA, 6Johns Hopkins Hospital, Baltimore, MD, 7UT Physicians Neurology-Texas Medical Center, Houston, TX, 8Genentech, Inc., South San Francisco, CA, 9UC Waddell Center for Multiple Sclerosis, Cincinnati, OH, United States

Background: Ocrelizumab (OCR) is a CD20-directed humanised monoclonal antibody approved for the treatment of relapsing and primary progressive multiple sclerosis (MS). The US prescribing information (USPI) for OCR recommends that patients initially complete two 300-mg infusions administered over 2.5 h, followed by single 600-mg infusions administered over 3.5 h. Reduced infusion time may improve the patient experience and optimise resource utilisation for healthcare practices.
Objectives: To report the safety of shorter OCR infusions from the Phase IIIb CHORDS (NCT02637856) extension substudy.
Methods: In the single-arm open-label CHORDS study, patients aged 18 to 55 y with relapsing-remitting MS and a suboptimal response to a previous disease-modifying treatment received two 300-mg OCR infusions separated by 2 wk, followed by 600-mg infusions every 24 wk; infusions were administered at the USPI-approved rate. Patients who tolerated OCR well up to Wk 72 (Dose 4) were eligible for an optional substudy at Wk 96 in which OCR 600 mg (Dose 5) was infused over 2 h. The primary endpoint of the substudy is the frequency of NCI CTCAE v4.0 Grade 3 and 4 infusion-related reactions (IRRs) after the shorter Wk 96 infusion; secondary endpoints include changes in physical findings and vital signs at Wk 96 and at a 30-day follow-up visit.
Results: As of 29 January 2019, 129 patients were enrolled in the substudy and all had completed the shorter infusion; 121 patients (93.8%) completed the shorter infusion in ≤2.5 h. Adverse events on the same day as the shorter infusion were reported in 19 patients (14.7%), including 16 (12.4%) with IRRs. No Grade 3/4 or serious IRRs were observed; 10 (7.8%) and 6 (4.7%) patients experienced Grade 1 and 2 IRRs, respectively. In comparison, 54 of 567 patients (9.5%) reported IRRs with the Wk 72 infusion (Dose 4) in the main CHORDS study in which OCR was infused over 3.5 h per USPI recommendations. Outcomes associated with the primary endpoint and other safety findings from the full population through the 30-d follow-up period will be presented.
Conclusions: These findings provide information on the safety of shorter OCR infusions. Specifically, in this substudy of CHORDS patients who completed and tolerated 4 doses of OCR per USPI recommendations, administration of OCR Dose 5 (600 mg) over a reduced infusion time of 2 h was not associated with an increased risk of serious, severe or life-threatening IRRs.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance were provided by Health Interactions, USA.
R. Bermel has received consulting fees from Biogen, F. Hoffmann-La Roche Ltd and Genentech, Inc., Genzyme and Novartis.
E. Waubant is site PI for ongoing trials with Genentech, Inc. and Biogen. She has research funding from NIH, PCORI, NMSS, and Race to Erase MS. She has received honoraria for lectures for Medscape, The Corpus and AAN, and for consulting work from Jazz Pharmaceuticals, Emerald and DBV. She is co-chief editor for MSARD.
G. Pardo has received personal compensation for consulting and/or speakers bureau from Biogen, Celgene, EMD Serono, Genentech, Inc., Novartis, Sanofi and Teva.
A. Bass has served on advisory boards and/or speaker bureaus and received research funding for Actelion, Biogen, EMD Serono, Genentech-Roche, Mallinckrodt, Novartis, Sanofi-Genzyme and TG Therapeutics.
P. Repovic has received consulting or speaking honoraria from Acorda, Alexion, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva
S. Newsome has been a consultant/advisor for Biogen, Genentech, Inc., Celgene, EMD Serono, Gerson Lehrman Group, Clinical Adjudication Committee Member for a medDay Pharmaceuticals clinical trial and has received research funding (paid directly to Institution) from Biogen, Genentech, Inc., Department of Defense, National MS Society, Patient-Centered Outcomes Research Institute.
J. Lindsey has nothing to disclose.
X. Ma is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
A. Pradhan is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
B. Musch is an employee of Genentech, Inc. and a shareholder of F. Hoffman-La Roche Ltd.
A. Zabeti received honoraria for speaker's bureau or advisory councils from ACORDA, BIOGEN, Celgene, Genentech, Genzyme/Sanofi, Novartis and Serono.

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