ACKNOWLEDGMENTS All authors participated in the development of the poster and approved the final poster for presentation. Editorial assistance in the development of this poster was provided by Jessica Donaldson of Fishawack Communications Ltd, Oxford, UK. This poster was previously presented at the European Academy of Allergy and Clinical Immunology Congress, June 17–21, 2017, Helsinki, Finland. FUNDING This study was funded by Novartis Pharmaceuticals Canada Inc. DISCLOSURES Authors declare the following, real or perceived conflicts of interest: GS, JH, WG, CL, and WHY received honoraria as investigators and consultants. GS received honoraria as speaker of this corresponding study. OC, FdT, and LR are employees of Novartis Pharmaceuticals. CONTACT INFORMATION Lenka Rihakova – Lenka.Rihakova@novartis.com Antonio Vieira – Antonio.Vieira@novartis.com Novartis Pharmaceuticals Canada: +1(514) 631 6775 STUDY DESIGN • OPTIMA is an international, multicenter, randomized, open-label, noncomparator study of two doses of omalizumab treatment (150 mg and 300 mg) across two dosing periods • In the initial dosing period, patients receive omalizumab by subcutaneous injection, at the randomized dose, every 4 weeks (Figure 1) • Subsequent dosing is determined based on the patient’s UAS7 response (Figures 2 and 3) • Patients are eligible for the OPTIMA study if they are adults diagnosed with CIU/CSU and have been exhibiting symptoms for at least 6 months prior to the study despite concurrent nonsedating H 1 -antihistamine therapy • Refractory to antihistamine therapy is defined as UAS7 ≥16 (scale 0−42) and itch component of UAS7 ≥8 (scale 0−21) despite treatment with an approved dose of nonsedating H 1 -antihistamine and no other concomitant CIU/CSU treatment for at least 7 consecutive days CONCLUSIONS • The OPTIMA study will allow better characterization of the appropriate omalizumab treatment regimen in patients with CIU/CSU who relapse or are not well controlled after initial treatment, by answering the following questions: − If a patient is well controlled and therefore treatment is stopped, will the patient relapse? How long will it take to relapse? − If treatment is restarted, will the patient respond to retreatment? − If the patient does not respond to omalizumab 150 mg, will step-up therapy help? − If the patient does not respond to omalizumab 300 mg, will treatment extension help? OBJECTIVES • PRIMARY: To assess the effect of optimized retreatment after relapse (defined as weekly urticaria activity score [UAS7] ≥16) in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who were clinically well controlled (UAS7 ≤6) following their first course of treatment with omalizumab • SECONDARY: Evaluation of dose step-up therapy in those who do not respond (UAS7 >6) to an initial dose of omalizumab 150 mg; assessment of the time to relapse in patients who initially were well controlled (UAS7 ≤6); and to evaluate the benefit of extending study treatment with omalizumab 300 mg in patients who are not yet clinically well controlled (UAS7 ≤6) after 24 weeks • EXPLORATORY: Evaluation of quality of life and occurrence of angioedema episodes DESIGN AND RATIONALE OF THE OPTIMA STUDY: RETREATMENT OR STEP-UP THERAPY WITH OMALIZUMAB IN PATIENTS WITH CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA (CIU/CSU) Gordon Sussman,1 Jacques Hébert,2 Wayne Gulliver,3 Charles Lynde,4 William H. Yang,5 Olivier Chambenoit,6 Gretty Deutsch,7 Frederica DeTakacsy,8 Lenka Rihakova8 1Department of Medicine, University of Toronto, Toronto, ON, Canada; 2Department of Medicine, Centre Hospitalier de l’Université Laval, Québec, QC, Canada; 3Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada; 4Lynde Institute for Dermatology, Markham, ON, Canada; 5Ottawa Allergy Research Corporation, University of Ottawa Medical School, Ottawa, ON, Canada; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Previously Novartis Pharmaceuticals Canada Inc, Dorval, QC, Canada; 8Novartis Pharmaceuticals Canada Inc, Dorval, QC, Canada Scan this QR code Visit the web at: http://novartis.medicalcongressposters.com/Default.aspx?doc=84898 Mobile Friendly e-Prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet Text Message (SMS) Text: Q84898 to: 8NOVA (86682) US Only +18324604729 North, Central and South Americas; Caribbean; China +447860024038 UK, Europe & Russia +46737494608 Sweden, Europe Standard data or message rates may apply. Presented at the Fall Clinical Dermatology Conference, October 12–15, 2017, Las Vegas, NV, USA Controlled at Week 24 – UAS7 ≤6 Not controlled at Week 24 UAS7 >6 Controlled at Week 24 – UAS7 ≤6 Controlled/ Mild UAS7 ≤16 Moderate/ Severe UAS7 ≥16 Omalizumab 300 mg 0 4 8 12 16 2420 0 4 8 0 412 W e ll c o n tr o ll e d w it h o u t re la p s e Weeks W e ll c o n tr o ll e d w it h r e la p s e N o t w e ll c o n tr o ll e d Follow-up Follow-up Follow-up Omalizumab 300 mg 1st Dosing Study treatment withdrawal 2nd Dosing Follow-up 0 4 8 Figure 2. Dosing scenarios for the omalizumab 300 mg treatment group. Patients who are well controlled (UAS7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. If relapse (UAS7 ≥16) occurs during withdrawal, patients are retreated in a second dosing period at the same dose (omalizumab 300 mg) for 12 weeks. If symptoms are not well controlled (UAS7 >6) in the initial dosing period, then patients extend treatment for 36 weeks of continuous omalizumab 300 mg treatment. 0 4 Follow-up Follow-up Follow-up Follow-up Controlled at every visit from Week 8 to Week 24 – UAS7 ≤6 Not controlled UAS7 >6 Controlled at every visit from Week 8 to Week 24 – UAS7 ≤6 Controlled/ Mild UAS7 ≤16 Moderate/ Severe UAS7 ≥16 Omalizumab 300 mg 0 4 8 12 16 2420 0 4 8 12 Omalizumab 150 mg W e ll c o n tr o ll e d w it h o u t re la p s e W e ll c o n tr o ll e d w it h r e la p s e N o t w e ll c o n tr o ll e d 1st Dosing Study treatment withdrawal 2nd Dosing 0 4 8Weeks Figure 3. Dosing scenarios for the omalizumab 150 mg treatment group. Patients who are well controlled (UAS7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. If relapse (UAS7 ≥16) occurs during the withdrawal period, patients are retreated in a second dosing period at the same omalizumab 150 mg dose for 12 weeks. If symptoms are not well controlled (UAS7 >6) during the initial omalizumab 150 mg dosing period, then patients step up to the omalizumab 300 mg dose at any protocol visit as early as Week 8 to start the second dosing period. Screen Washout Omalizumab 150 mg Omalizumab 300 mg G ro u p A G ro u p B Follow- up UAS7 ≤6 UAS7 <16 Stop therapy Omalizumab 300 mg Omalizumab 150 mg R a n d o m iz a ti o n 4 :3 −5 to −1Week 0 4 8 12 16 2420 0 4 8 12 0 4 UAS7 >6 UAS7 ≤6 UAS7 <16 Stop therapy Omalizumab 300 mg Omalizumab 300 mg UAS7 ≥16 UAS7 ≥16 UAS7 >6 Screen 1st Dosing Study treatment withdrawal 2nd Dosing Follow- up 0 4 8 Figure 1. OPTIMA Study design. The study includes 5 phases: screening; initial dosing period; withdrawal; a second dosing period for retreatment, dose step-up, or dose extension based on UAS7 response; and follow-up. SAMPLE SIZE AND ANALYSIS Sample size • The study has been planned to enroll and randomize a total of 320 patients, in a ratio of 4:3, to the doses of omalizumab 150 mg or 300 mg. The sample size is estimated on the basis of assessing the effect of retreatment following relapse (primary endpoint) Primary endpoint • Proportion of patients who achieved a UAS7 ≤6 at the end of the second dosing period, after being clinically well controlled (UAS7 ≤6) in the initial dosing period followed by relapse (UAS7 ≥16) when treatment was discontinued Secondary endpoints • Difference in the UAS7 between the start and the end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • The proportion of patients who were clinically well controlled (UAS7 ≤6) at the end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • The time to relapse (UAS7 ≥16) after withdrawal of omalizumab in patients who were clinically well controlled following their first course of omalizumab treatment • Difference in the UAS7 between the end of the initial dosing period and the end of the second dosing period in patients who extended treatment with omalizumab 300 mg • The UAS7 change from baseline measured at the end of the initial dosing period in patients who received omalizumab 300 mg • The UAS7 change from baseline measured at the end of the second dosing period in all patients • The proportion of patients who remain well controlled (UAS7 ≤6) or who have achieved a UAS7 =0 at Week 8 of the initial dosing period versus Week 8 of the second dosing period • The proportions of patients who remain clinically well controlled (UAS7 ≤6) at any visit starting at Week 8 of the initial dosing period until the end of the first dosing period UAS7, weekly urticaria activity score. UAS7, weekly urticaria activity score. UAS7, weekly urticaria activity score.