OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in Chronic Spontaneous Urticaria (CSU) Patients (OPTIMA)

OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in CSU Patients

This trial assessed the efficacy of optimized re-treatment therapy with omalizumab (150mg or 300mg) after relapse, in participants with Chronic Spontaneous Urticaria who were clinically well-controlled following their first course of treatment with omalizumab (150mg or 300mg). The study also assessed the benefit of uptitrating to 300mg dose in participants who were not well-controlled following their initial course of treatment with omalizumab 150mg, as well as the benefit of treatment extension of those patients who were not well-controlled following their initial course of treatment with omalizumab 300mg.

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: omalizumab; Drug: omalizumab

Detailed Description

The study consisted of 5 phases.

Phase 1 (Screening): At the first visit (Screening Visit), the participant was provided informed consent and then completed all screening visit assessments. During this visit, all CIU/CSU treatments taken by the participant were documented. Any protocol-defined prohibited CIU/CSU treatments were stopped at this visit, and the participant underwent a wash-out period of 1-5weeks (refer to study protocol for medication wash-out times) prior to Phase 2 Visit1. Only non-sedating H1- antihistamines, at locally-approved dosages, were allowed to be continued during the Screening Period and throughout the rest of the study. All participants also needed to complete daily diary during the entire screening period.

Phase 2 (Initial Dosing Period): Following completion of Phase 1, eligible participants were randomly assigned (in a 4:3 ratio) to either Group A or Group B. Participants in Group A were treated with omalizumab 150mg by subcutaneous (SC) injection every 4 weeks during the 24-week Phase 2 (Initial Dosing Period), while participants in Group B were treated with omalizumab 300mg every 4 weeks during this period. Randomization to treatment groups was stratified at Phase 2 Visit 1 by geographic location of the study site (i.e. Canada or Latin America), baseline presence/absence of angioedema and baseline UAS7 score (collected at Phase 2 Visit 1). At the end of Phase 2, all participants with a UAS7 score ≤ 6 entered Phase 3 (Study Treatment Withdrawal Period). Group A participants who had a UAS7 > 6 at any visit of Phase 2 starting at Week 8 (Phase2-Visit3) skipped Phase 3 and moved directly to Phase 4 (Second Dosing Period) and received 300 mg Omalizumab (step-up). Group B participants who had a UAS7 >6 at the end of Phase 2 skipped Phase 3 and moved directly to Phase 4.

Phase 3 (Study Treatment Withdrawal Period): During Phase 3 (Study Treatment Withdrawal Period), no study treatment (omalizumab) was given and participants continued to visit the study center at 4-week intervals (to a maximum of 8 weeks). If a UAS7 score ≥16 was observed during Phase 3 (Study Treatment Withdrawal Period), the participant moved directly to Phase 4 (Second Dosing Period). If a participant completed the full 8 weeks of Phase 3 (Study Treatment Withdrawal Period) with a UAS7 score <16, the participant was moved directly to Phase 5 (Follow-up Period).

Phase 4 (Second Dosing Period)

• Group A participants who relapsed (UAS7 ≥16) during Phase 3 (Study Treatment Withdrawal Period) were retreated with omalizumab 150mg by SC injection every 4 weeks during the 12-week Phase 4 (Second Dosing Period)
• Group A participants who were not clinically well-controlled at week 8 of Phase 2 (Initial Treatment Period) or any subsequent visit in Phase 2 moved to Phase 4 (Second Dosing Period) immediately during which their study treatment was up-titrated to 300mg by SC injection every 4 weeks for 12 weeks.
• Group A participants who had their symptoms well controlled at week 24 (UAS7≤6) but did not relapse during the 8 weeks Study Treatment withdrawal period (UAS7<16) moved directly to Phase 5, Follow up period.
• Group B participants who relapsed during Phase 3 (Study Treatment Withdrawal Period) were retreated with omalizumab 300mg by SC injection every 4 weeks during the 12- week Phase 4 (Second Dosing Period)
• Group B participants who were not clinically well-controlled at week 24 of Phase 2 (Initial Treatment Period) moved to Phase 4 (Second Dosing Period) immediately during which their study treatment remained 300mg by SC injection every 4 weeks for 12 weeks. In case the treating physician and the participant decided not to extend treatment, they could move directly from Phase 2 (Initial Treatment Period) to Phase 5 (Follow- up Period).
• Group B participants who had their symptoms well controlled at week 24 (UAS7≤6) but did not relapse during the 8 weeks Study Treatment withdrawal period (UAS7<16) moved directly to Phase 5, Follow up period.

Phase 5 (Follow-up Period)

• Participants who did not relapse (UAS7 <16) following completion of Phase 3 (Study Treatment Withdrawal Period) entered the 4-week Phase 5 (Follow-up Period).
• Group B participants who did not respond during their initial 24-week treatment period (Phase 2), and who did not wish to extend their treatment into Phase 4 (Second Dosing Phase) were allowed to move directly into the 4-week Phase 5 (Follow-up Period).
• All participants who completed Phase 4 (Second Dosing Period) entered the 4-week Phase 5 (Follow-up Period).

During Phase 5 (Follow-up Period), participants continued to only receive non-sedating H1- antihistamines at approved dosages. Omalizumab was not allowed to be administered during this period.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABE
    • Novartis Investigative Site
  • Salta, Argentina, A4400ERH
    • Novartis Investigative Site
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, 1629
      • Novartis Investigative Site
  • Rosario
    • Santa Fe, Rosario, Argentina, S2000DBS
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CXH
      • Novartis Investigative Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 40110-060
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Novartis Investigative Site
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • Novartis Investigative Site
  • Sao Paulo
    • Alphaville / Barueri, Sao Paulo, Brazil, 06454-010
      • Novartis Investigative Site
• Canada
  • Quebec, Canada, GIV 4M6
    • Novartis Investigative Site
  • Toronto, Canada, M4C 5M5
    • Novartis Investigative Site
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • Novartis Investigative Site
    • Vancouver, British Columbia, Canada, V6H 3K2
      • Novartis Investigative Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 4Y3
      • Novartis Investigative Site
    • St. John's, Newfoundland and Labrador, Canada, A1C 2H5
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3R4
      • Novartis Investigative Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Novartis Investigative Site
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Novartis Investigative Site
    • Hamilton, Ontario, Canada, L8S 1G5
      • Novartis Investigative Site
    • Kingston, Ontario, Canada, K7L 2V7
      • Novartis Investigative Site
    • Markham, Ontario, Canada, L3P 1A8
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1Y 4G2
      • Novartis Investigative Site
    • Peterborough, Ontario, Canada, K9J 5K2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4V 1R2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 1E2
      • Novartis Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Novartis Investigative Site
    • Windsor, Ontario, Canada, N8X 2G1
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 8420383
    • Novartis Investigative Site
  • Santiago, Chile, 8207257
    • Novartis Investigative Site
• Dominican Republic
  • Republica Dominicana
    • Santo Domingo, Republica Dominicana, Dominican Republic
      • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01015
    • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • Delegacion Tlalpan, Distrito Federal, Mexico, 14050
      • Novartis Investigative Site
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45190
      • Novartis Investigative Site
• Panama
  • Panama, Panama
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Men or women at least 18 years of age at time of screening.
• Having a diagnosis of CSU and the presence of symptoms for ≥6 months prior to the screening visit.
• Presence of itch and hives for ≥6 consecutive weeks at any time prior to the screening visit despite concurrent use of non-sedating H1-antihistamine treatment
• Patient must have been on an approved dose of non-sedating H1-antihistamine for CSU, and no other concomitant CSU treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must document current use on the day of the randomization visit.

Key Exclusion Criteria:

• Patients having a clearly defined underlying etiology for chronic urticaria other than CSU including the following urticarias: acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact
• Patients with other skin disease associated with itch that could interfere with study outcomes and/or compromise the safety of the patient
• Patients with evidence of parasitic infection
• Patients with a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Pregnant or nursing (lactating) women,
• Women of child-bearing potential, unless they are using effective methods of contraception during dosing of study treatment.
• Patients who are unable or unwilling to comply with study procedures, attend scheduled study visits, complete questionnaires and daily diaries, or who may otherwise be unable to comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: omalizumab 150mg; Participants received 150mg omalizumab every 4 weeks during the initial dosing phase (24 weeks). A second dosing period (at 150mg or 300mg) may have been implemented based on protocol-defined assessment criteria.	Drug: omalizumab; 150mg omalizumab via sub-cutaneous injection once every 4 weeks; Drug: omalizumab; 300mg omalizumab via sub-cutaneous injection once every 4 weeks
Experimental: omalizumab 300mg; Participants received 300mg omalizumab every 4 weeks during the initial dosing phase (24 weeks). A second dosing period may have been implemented based on protocol-defined assessment criteria.	Drug: omalizumab; 150mg omalizumab via sub-cutaneous injection once every 4 weeks; Drug: omalizumab; 300mg omalizumab via sub-cutaneous injection once every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were Clinically Well-controlled (UAS7<=6) After the Initial Dosing Period, Relapsed (UAS7>=16) When Treatment Was Discontinued, and Who Achieved a UAS7 Score <=6 at the End of the Second Dosing Period (Retreatment A2 and B2)	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the last 7 days of the second dosing period.	Last 7 days of second dosing period, 44 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Difference in Urticaria Activity Score Over 7 Days (UAS7) Between the Start and End of the Second Dosing Period, in Participants That Step-up Treatment Dose During the Initial Dosing Period (Step-up A3)	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the 7 days prior to the second dosing period, and the last 7 days of the second dosing period. A negative change indicates improvement.	7 days prior to start of second dosing period and last 7 days of Second Dosing Period
Number of Participants With Urticaria Activity Score Over 7 Days (UAS7)≤6 at the End of the Second Dosing Period, in Participants Who Stepped-up Treatment Dosing (Step-up A3)	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the last 7 days of the second dosing period.	Last 7 days of the second dosing period
Time to Relapse (Urticaria Activity Score Over 7 Days (UAS7) ≥ 16) After Drug Withdrawal in Participants Who Responded to Initial Dosing Period (Retreatment A2 and B2)	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the time between end of initial dosing period to first occurence of UAS7 ≥ 16 will be evaluated.	study drug withdrawal period, weeks 24 through 32
Difference in Urticaria Activity Score Over 7 Days (UAS7) Between End of Initial Dosing Period and the End of the Second Dosing Period, in Group B3 Participants Who Did Not Respond to the Initial Dosing Period	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the last 7 days of the initial dosing period and the last 7 days of the second dosing period. A negative change indicates improvement.	last 7 days of initial dosing period, week 24, and last 7 days of second dosing period, week 36
The Change in Urticaria Activity Score Over 7 Days (UAS7) From Baseline to Week 24 in Group B Participants	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the 7-day period prior to Baseline visit and the last 7 days prior to the week 24 visit of initial dosing period. A negative change from baseline indicates improvement.	7 days prior to Baseline visit, and last 7 days prior to week 24 of the initial dosing period
Change in Urticaria Activity Score Over 7 Days (UAS7) Between Baseline and End of Second Dosing Period	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from the 7 days before Baseline and the last 7 days of the second dosing period.	7 days prior to Baseline visit, and last 7 days of second dosing period
The Number of Participants Who Remained Well-controlled (UAS7<=6) or Who Had Achieved UAS=0 at Phase 4 (Second Dosing Period) Week 8 During Retreatment After Being Well Controlled or Achieving UAS7=0 at Phase 2 (Initial Dosing Period) Week 8	The UAS7 is a 7-day composite self-reported evaluation of itch (daily score 0-3) plus number of hives (daily score 0-3). The worst possible daily UAS score is 6, and the worst possible UAS7 score is 42. For this outcome, the participant's self-reported UAS7 score will be drawn from week 8 of initial dosing phase and week 8 of second dosing phase.	Week 8 of initial dosing phase and week 8 of second dosing phase

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Sussman G, Hebert J, Gulliver W, Lynde C, Yang WH, Papp K, Gooderham M, Chambenoit O, Khalil S, DeTakacsy F, Vieira A, Rihakova L. Omalizumab Re-Treatment and Step-Up in Patients with Chronic Spontaneous Urticaria: OPTIMA Trial. J Allergy Clin Immunol Pract. 2020 Jul-Aug;8(7):2372-2378.e5. doi: 10.1016/j.jaip.2020.03.022. Epub 2020 Apr 6.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): November 3, 2016
• Study Completion (Actual): November 3, 2016

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 10, 2014
• First Posted (Estimate): June 11, 2014

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: chronic spontaneous urticaria, CSU, chronic idiopathic urticaria, CIU, hives, angioedema, itch
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Immunologic Factors; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Antibodies, Monoclonal; Omalizumab
• Other Study ID Numbers: CIGE025ECA01