Study to Compare Efficacy and Safety of TEV-45779 With XOLAIR (Omalizumab) in Adults With Chronic Idiopathic Urticaria

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study to Evaluate the Efficacy, Safety, Tolerability, and Immunogenicity of TEV-45779 Compared to XOLAIR (Omalizumab) in Patients With Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine (H1) Treatment.

Conditions
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Chronic Urticaria

Intervention / Treatment
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* Combination Product: TEV-45779
* Combination Product: XOLAIR® Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CIU refractory to H1 antihistamines for ≥3 months Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-45779-300 mg Main Treatment period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 0, 4, 8 | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>|
| Active Comparator: Xolair-300 mg Main Treatment Period<br>XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 0, 4, 8 | Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|
| Experimental: TEV-45779-150 mg Main Treatment period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 0, 4, 8 | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>|
| Active Comparator: Xolair-150 mg Main Treatment Period<br>XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 0, 4, 8 | Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|
| Experimental: TEV-45779-300 mg Main / TEV45779-300 mg Transition Period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to TEV-45779-300 mg in the Main Treatment period. | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>|
| Experimental: Xolair-300 mg Main / TEV45779-300 mg Transition Period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to Xolair-300 mg in the main treatment period. | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|
| Active Comparator: Xolair-300 mg Main / Xolair-300 mg Transition Period<br>XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered twice (total dosage 300 mg) at week 12,16,20 in patients that were randomized to Xolair-300 mg in the main treatment period. | Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|
| Experimental: TEV-45779-150 mg Main / TEV-45779-150 mg Transition Period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to TEV-45779-150 mg in the main treatment period. | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>|
| Experimental: Xolair-150 mg Main / TEV-45779-150 mg Transition Period<br>TEV-45779 (Omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to XOLAIR-150 mg in the main treatment period. | Combination Product: TEV-45779<br>* TEV-45779 (Omalizumab) solution for injection 150 mg/mL prefilled syringe<br>Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|
| Active Comparator: Xolair-150 mg Main / Xolair-150 mg Transition Period<br>XOLAIR (omalizumab) injection 150 mg/mL pre-filled syringe administered with one placebo injection at week 12,16,20 in patients that were randomized to XOLAIR -150 mg in the main treatment period. | Combination Product: XOLAIR® Injection<br>* XOLAIR (omalizumab) injection is supplied as a single dose PFS. Each PFS of XOLAIR contains 150 mg of omalizumab in 1 mL of solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the ISS7 at Week 12 between TEV 45779 300 mg and XOLAIR 300 mg | ISS 7 is a weekly itch severity score calculated as sum of the daily itch severity score for 7 days, on a scale of 0 to 3 (0=none to 3=intense/severe). | Baseline and week 12 | 
| Relative potency of TEV 45779 and XOLAIR | Relative potency TEV45779 to the Xolair defined as the dose of TEV45779 that produces the same biological response as one unit of the dose of the Xolair. The relative potency and its CI will be measured by change in ISS7 at Week 12 using a 4 point assay based on the 300 mg and 150 mg dose levels of each product. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the ISS7 at Week 12 | ISS 7 is a weekly itch severity score calculated as sum of the daily itch severity score for 7 days, on a scale of 0 to 3 (0=none to 3=intense/severe). | Baseline, week 4 and week 12 | 
| Change from baseline in the UAS7 at Week 12 | Change from baseline in the Urticaria Activity Score (UAS) - sum of the daily number of wheals score and itch severity score over 7 days, range from 0 (minimum) to 6 (maximum)) at Week 12. | Baseline and week 12 | 
| Percentage of patients with a UAS7 ≤6 at Week 12 | Percentage of patients with a weekly Urticaria Activity Score ≤6 at Week 12 | week 12 | 
| Percentage of complete responders (UAS7=0) at Week 12 | Percentage of complete responders with weekly Urticaria Activity Score =0 at Week 12 | week 12 | 
| Change from baseline in the physician's (in-clinic) assessment of UAS7 at Week 12 | Change from baseline in the physician's (in-clinic) assessment of weekly Urticaria Activity Score at Week 12. | Baseline and week 12 | 
| Change from baseline in the weekly number of wheals score at Week 12 | Change from baseline in the weekly number of wheals score at Week 12 | Baseline and week 12 | 
| Change from baseline in the weekly size of the largest wheals score at Week 12 | Change from baseline in the weekly size of the largest wheals score at Week 12 | Baseline and week 12 | 
| Time to MID response in ISS7 score by Week 12 | Time to minimally important difference (MID) defined as a reduction from baseline in ISS7 of ≥5 points) response in ISS7 score by Week 12 | Baseline till week 12 | 
| Percentage of ISS7 MID responders at Week 12 | Percentage of patients with minimally important difference defined as reduction of ≥5 points from baseline in ISS7 at Week 12. | Baseline and week 12 | 
| Percentage of angioedema-free days from Week 4 to Week 12 | Percentage of angioedema-free days from Week 4 to Week 12 | week 4 and week 12 | 
| Change from baseline in the overall DLQI score at Week 12 | Change from baseline in the overall dermatology life quality index (DLQI) score at Week 12; comparisons of TEV 45779 and XOLAIR treatment arms. The DLQI consists of 10 questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired | Baseline and week 12 | 
| Change from Week 12 in ISS7 at Week 24 | Change from Week 12 in ISS7 at Week 24 | week 12 and week 24 | 
| Change from Week 12 in ISS7 at Week 40 | Change from Week 12 in ISS7 at Week 40. | week 12 and week 40 | 
| Change from Week 12 in the UAS7 at Week 24 | Change from Week 12 in the UAS7 (sum of the daily number of wheals score and itch severity score over 7 days) at Week 24. | week 12 and week 24 | 
| Change from Week 12 in the physician's (in-clinic) assessment of UAS7 at Week 24 | Change from Week 12 in the physician's (in-clinic) assessment of UAS7 at Week 24 | week 12 and week 24 | 
| Change from Week 12 in the weekly number of wheals score at Week 24 | Change from Week 12 in the weekly number of wheals score at Week 24. | week 12 and week 24 | 
| Change from Week 12 in the weekly number of wheals score at Week 40 | Change from Week 12 in the weekly number of wheals score at Week 40. | week 12 and week 40 | 
| Change from Week 12 in the weekly number of the largest wheals score at Week 24 | Change from Week 12 in the weekly number of the largest wheals score at Week 24. | week 12 and week 24 | 
| Change from Week 12 in the weekly number of the largest wheals score at Week 40 | Change from Week 12 in the weekly number of the largest wheals score at Week 40. | week 12 and week 40 | 
| Percentage of angioedema-free days from Week 12 to Week 24 | Percentage of angioedema-free days from Week 12 to Week 24 | week 12 and week 24 | 
| Change from Week 12 in the overall DLQI score at Week 24 | Change from Week 12 in the overall dermatology life quality index (DLQI) score at Week 24 | week 12 and week 24 | 
| Change from Week 12 in the overall DLQI score at Week 40 | Change from Week 12 in the overall dermatology life quality index (DLQI) score at Week 40 | week 12 and week 40 | 
| Incidence of adverse event and withdrawals due to adverse events in the main period | Number of patients reporting at least one treatment-emergent adverse event up to week 12 | Baseline till week 12 | 
| Incidence of adverse event in the transition and follow up period | Number of patients reporting at least one treatment-emergent adverse event from week 12 till week 40 | week 12 till week 40 | 
| Incidence of antidrug antibodies (ADAs) in the main treatment period | Number of patients with confirmed positive antidrug antibodies (ADAs) post-baseline up to week 12 | Baseline till week 12 | 
| Incidence of antidrug antibodies (ADAs) in the transition and follow up period | Number of patients with confirmed positive antidrug antibodies (ADAs) post-week 12 up to week 40 | week 12 till week 40 |