Study to Compare Efficacy and Safety of TEV-45779 With XOLAIR (Omalizumab) in Adults With Chronic Idiopathic Urticaria
- Conditions
- Chronic Urticaria
- Registration Number
- NCT04976192
- Lead Sponsor
- Teva Pharmaceuticals USA
- Brief Summary
The purpose of the study is to compare the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity of TEV-45779 compared to XOLAIR in patients with Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) who remain symptomatic on H1 antihistamine treatment.
- Detailed Description
This is a multicenter, randomized, double-blind study to demonstrate similar efficacy and safety of TEV-45779 compared to XOLAIR administered sc at doses of 300 mg or 150 mg every 4 weeks for 24 weeks (6 treatments) in patients with Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite antihistamine (H1) treatment. This study will consist of a screening period (up to 2 weeks), a 24-week treatment period consisting of a 12-week double-blind main treatment period and a 12-week double-blind transition period, which is followed by a 16-week follow-up period. The total duration of the study is up to 42 weeks.
At baseline, patients will be randomized in a 2:2:1:1 ratio to receive the first 3 treatments of TEV-45779 300 mg, XOLAIR 300 mg, TEV-45779 150 mg or XOLAIR 150 mg (main treatment period). At Week 12, prior to receiving their fourth dose of study medication, patients in the XOLAIR 300 mg and the XOLAIR 150 mg treatment groups will be randomized 1:1 to receive 3 additional doses of XOLAIR (at the same dose level as prior to randomization, or switch to 3 doses of TEV-45779 (transition period) at the same dose level as prior to randomization. All patients in the TEV-45779 groups will continue to receive TEV-45779 at the same dose levels.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 608
- Diagnosis of CIU refractory to H1 antihistamines for ≥3 months
- Chronic urticaria with clearly defined underlying etiology
- Other skin disease associated with itch
- Evidence of parasitic infection on stool evaluation for ova and parasites
- History of anaphylactic shock
- Hypersensitivity to omalizumab or any component of the formulation
- Required background therapy with other than protocol-defined antihistamines
- Any medical condition that could jeopardize or would compromise the patient's safety or ability to participate in this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Change From Baseline in the ISS7 at Week 12, TEV-45779 High Dose Compared to XOLAIR High Dose (For European Medicines Agency [EMA] Submission) Baseline, Week 12 The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching. Least square (LS) mean and 95% confidence interval (CI) were calculated using analysis of covariance (ANCOVA) model. Multiple imputation performed both for the participants having missing ISS7 at week 12 and for participants using any disallowed concomitant medication.
Change From Baseline in the ISS7 at Week 12, TEV-45779 High Dose Compared to XOLAIR High Dose (For Food and Drug Administration [FDA] Submission) Baseline, Week 12 The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching. LS mean and 90% CI were calculated using ANCOVA model. Multiple imputation performed for the participants having missing ISS7 at week 12.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the ISS7 at Weeks 4 and 12 Baseline, Weeks 4 and 12 The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching. The observed mean and standard deviation values are reported here with no imputation performed.
Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 Baseline, Week 12 The UAS was a composite eDiary-recorded score with numeric severity intensity ratings on a scale of 0 - 3 (0 = none to 3 = intense/severe) for (1) the number of wheals (hives); and (2) the intensity of the itch separately, measured twice daily (morning and evening). The daily UAS was the average of the morning and evening scores, which ranged from 0 (none) to 6 (severe). The UAS7 was the sum of the daily UAS scores over 7 days, which ranged from 0 (minimum) to 42 (highest urticaria severity). Higher scores indicated greater severity of urticaria symptoms.
Percentage of Participants With a UAS7 Score ≤6 at Week 12 Week 12 The UAS was a composite eDiary-recorded score with numeric severity intensity ratings on a scale of 0 - 3 (0 = none to 3 = intense/severe) for (1) the number of wheals (hives); and (2) the intensity of the itch separately, measured twice daily (morning and evening). The daily UAS was the average of the morning and evening scores, which ranged from 0 (none) to 6 (severe). The UAS7 is the number of participants achieving the endpoint of less than or equal to 6. UAS7 was calculated as the sum of the daily UAS scores over 7 days, which ranged from 0 (minimum) to 42 (highest urticaria severity). Higher scores indicated greater severity of urticaria symptoms.
Percentage of Complete Responders (UAS7 Score = 0) at Week 12 Week 12 The UAS was a composite eDiary-recorded score with numeric severity intensity ratings on a scale of 0 - 3 (0 = none to 3 = intense/severe) for (1) the number of wheals (hives); and (2) the intensity of the itch separately, measured twice daily (morning and evening). The daily UAS was the average of the morning and evening scores, which ranged from 0 (none) to 6 (severe). The UAS7 was the sum of the daily UAS scores over 7 days, which ranged from 0 (minimum) to 42 (highest urticaria severity). Higher scores indicated greater severity of urticaria symptoms. Complete responders were participants with a UAS7 score = 0.
Change From Baseline in the Physician's (In-clinic) Assessment of UAS at Week 12 Baseline, Week 12 Physician's (in-clinic) assessment of UAS score was performed using the in-clinic UAS. The physician, or the person designated, provided the sum of the score of the participant's urticaria lesions (number of wheals \[hives\]) and pruritus (itch) reflective of the participant's condition over the 12 hours prior to the visit using the rating scale of 0 - 6 (0 = none to 6 = intense/severe). Higher scores indicated greater severity of urticaria symptoms.
Change From Baseline in the Weekly Number of Wheals Score at Week 12 Baseline, Week 12 The wheals (hives) severity score, defined by number of wheals (hives), was recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly number of wheals score was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 (no wheals) - 21 (highest hives activity).
Change From Baseline in the Weekly Size of the Largest Wheals Score at Week 12 Baseline, Week 12 The weekly size of the largest wheals score was calculated from the eDiary data. A wheal score of 0 was assigned when \<10 small wheals (diameter \<3 centimeters \[cm\]) were present, presence of 10-50 small wheals or less than 10 large wheals (diameter \>3 cm) was denoted by score of 1. A score of 2 was assigned when more than 50 small wheals or 10 to 50 large wheals were present. A score of 3 denoted wheals covering almost the entire body surface area. A weekly score was defined as the sum of the available daily size of the largest wheals scores in that week, divided by the number of days for which a daily score was available, multiplied by 7. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severity.
Time to Minimally Important Difference (MID) Response in ISS7 Score Baseline up to Week 12 Time to MID response was defined as time to a reduction from baseline in ISS7 of ≥5 points in ISS7 score by Week 12.
Percentage of ISS7 MID Responders at Week 12 Week 12 A responder was defined as a participant with a reduction from baseline in ISS7 of ≥5 points in ISS7 score.
Percentage of Angioedema-Free Days From Week 4 to Week 12 Week 4 to Week 12 Percentage of angioedema-free days from Week 4 to Week 12 were calculated based on the diary data as the number of days in the diary between the dates of Week 4 and Week 12 visits with no angioedema episodes, divided by the total number of days with diary entries in this time span \* 100%.
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 Baseline, Week 12 The DLQI consisted of 10 questions concerning participants' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. The DLQI total score was calculated by adding the score of each question (scored as follows: Very much = 3; Yes \[in question 7.a\] = 3; A lot = 2; A little = 1; Not at all = 0; Not relevant = 0; No \[in question 7.a\] = 0; Question unanswered = 0), resulting in a maximum of 30 and a minimum of 0. The higher the score, the more the quality of life was impaired. A score higher than 10 indicated that the participant's life was being severely affected by their skin disease.
Change From Week 12 in ISS7 at Weeks 24 and 40 Week 12, Weeks 24 and 40 The severity of the itch was recorded by the participants twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly itch score (ISS7) was defined as the sum of the available daily itch severity scores in that week, divided by the number of days for which a daily itch severity score was available, multiplied by 7. The daily ISS was calculated as the average of the morning and evening scores. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severe itching.
Change From Week 12 in the UAS7 at Week 24 Week 12, Week 24 The UAS was a composite eDiary-recorded score with numeric severity intensity ratings on a scale of 0 - 3 (0 = none to 3 = intense/severe) for (1) the number of wheals (hives); and (2) the intensity of the itch separately, measured twice daily (morning and evening). The daily UAS was the average of the morning and evening scores, which can range from 0 (none) to 6 (severe). The UAS7 was the sum of the daily UAS scores over 7 days, which can range from 0 (minimum) to 42 (highest urticaria severity). Higher scores indicated greater severity of urticaria symptoms.
Change From Week 12 in the Physician's (In-clinic) Assessment of UAS7 at Week 24 Week 12, Week 24 Physician's (in-clinic) assessment of UAS score was performed using the in-clinic UAS. The physician, or the person designated, provided the sum of the score of the participant's urticaria lesions (number of wheals \[hives\]) and pruritus (itch) reflective of the participant's condition over the 12 hours prior to the visit using the rating scale of 0 - 6 (0 = none to 6 = intense/severe). Higher scores indicated greater severity of urticaria symptoms.
Change From Week 12 in the Weekly Number of Wheals Score at Weeks 24 and 40 Week 12, Weeks 24 and 40 The wheals (hives) severity score, defined by number of wheals (hives), was recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly number of wheals score was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 (no wheals) - 21 (highest hives activity).
Change From Week 12 in the Weekly Size of the Largest Wheals Score at Weeks 24 and 40 Week 12, Weeks 24 and 40 The weekly size of the largest wheals score was calculated from eDiary data. A wheal score of 0 was assigned when \<10 small wheals (diameter \<3 cm) were present, presence of 10-50 small wheals or less than 10 large wheals (diameter \>3 cm) was denoted by score 1. A score of 2 was assigned when more than 50 small wheals or 10 to 50 large wheals were present. A score of 3 denoted wheals covering almost the entire body surface area. A weekly score was defined as sum of available daily size of the largest wheals scores in that week, divided by the number of days for which a daily score was available, multiplied by 7. The possible range of the weekly score was therefore 0 (best score) to 21 (worst score) with higher scores indicating more severity.
Percentage of Angioedema-Free Days From Week 12 to Week 24 Week 12 to Week 24 Percentage of angioedema-free days from Week 12 to Week 24 was calculated based on the diary data as the number of days in the diary between the dates of Week 12 and Week 24 visits with no angioedema episodes, divided by the total number of days with diary entries in this time span \* 100%.
Change From Week 12 in the Overall DLQI Score at Weeks 24 and 40 Week 12, Weeks 24 and 40 The DLQI consisted of 10 questions concerning participants' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. The DLQI total score was calculated by adding the score of each question (scored as follows: Very much = 3; Yes \[in question 7.a\] = 3; A lot = 2; A little = 1; Not at all = 0; Not relevant = 0; No \[in question 7.a\] = 0; Question unanswered = 0), resulting in a maximum of 30 and a minimum of 0. The higher the score, the more the quality of life was impaired. A score higher than 10 indicated that the participant's life was being severely affected by their skin disease.
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) in the Main Treatment Period Baseline up to Week 12 An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred or worsened on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With at Least One TEAE Week 12 up to Week 24 Week 12 up to Week 24 An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred or worsened on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Antidrug Antibodies (ADAs) in the Main Treatment Period Baseline up to Week 12 Number of participants with positive ADA, positive ADA not treatment-related, and negative ADA are reported.
Number of Participants With ADAs From Week 12 to Week 24 Week 12 up to Week 24 Number of participants with positive ADA, positive ADA not treatment-related, and negative ADA are reported.
Trial Locations
- Locations (9)
10008
🇺🇸Bakersfield, California, United States
Site 10001
🇺🇸Clearwater, Florida, United States
10012
🇺🇸Coral Gables, Florida, United States
10006
🇺🇸Kissimmee, Florida, United States
10014
🇺🇸Maitland, Florida, United States
10005
🇺🇸Miami, Florida, United States
10009
🇺🇸Tampa, Florida, United States
10007
🇺🇸Troy, Michigan, United States
10004
🇺🇸Salt Lake City, Utah, United States
10008🇺🇸Bakersfield, California, United States