Clinical trial NCT02161562: OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in Chronic Spontaneous Urticaria (CSU) Patients
Official title: OPTIMA: Efficacy of Optimized Re-treatment and Step-up Therapy With Omalizumab in CSU Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: chronic spontaneous urticaria, CSU, chronic idiopathic urticaria, CIU, hives, angioedema, itch
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-06-11
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Last 7 days of second dosing period, 44 weeks
Secondary outcomes:
measure: 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)
timeFrame: 7 days prior to start of second dosing period and last 7 days of Second Dosing Period
measure: 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)
timeFrame: Last 7 days of the second dosing period
measure: 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)
timeFrame: study drug withdrawal period, weeks 24 through 32
measure: 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
timeFrame: last 7 days of initial dosing period, week 24, and last 7 days of second dosing period, week 36
measure: The Change in Urticaria Activity Score Over 7 Days (UAS7) From Baseline to Week 24 in Group B Participants
timeFrame: 7 days prior to Baseline visit, and last 7 days prior to week 24 of the initial dosing period
measure: Change in Urticaria Activity Score Over 7 Days (UAS7) Between Baseline and End of Second Dosing Period
timeFrame: 7 days prior to Baseline visit, and last 7 days of second dosing period
measure: 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
timeFrame: Week 8 of initial dosing phase and week 8 of second dosing phase
Other outcomes:
Locations:
city: Pilar
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
state: Rosario
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Salta
country: Argentina
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Alphaville / Barueri
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: St. John's
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Barrie
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Kingston
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Markham
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Peterborough
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Waterloo
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Windsor
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santo Domingo
country: Dominican Republic
facility: Novartis Investigative Site
state: Republica Dominicana
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Delegacion Tlalpan
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Zapopan
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Panama
country: Panama
facility: Novartis Investigative Site
Study officials:
References:
citation: 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.