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Study to Evaluate the Therapeutic Equivalence of SYN008 Versus Xolair® in the Treatment of Patients With Refractory Chronic Spontaneous Urticaria

Primary Purpose

Chronic Spontaneous Urticaria

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
SYN008
Omalizumab for injection
Sponsored by
CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Spontaneous Urticaria

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diagnosis of CSU refractory to H1AH at the time of randomization, as defined by all of the following:

    • CSU diagnosis for ≥ 6 months;
    • The presence of itch and hives for ≥ 6 consecutive weeks within one year prior to randomization despite use of H1AH treatment during this time period;
    • UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1);
    • In-clinic UAS ≥ 4 on at least one of the screening visit days;
    • Patients must have been on an approved dose of an H1AH for CSU for at least the 3 consecutive days immediately prior to the screening visit and must have documented current use on the day of the initial screening visit.
  2. Voluntarily sign the informed consent form. Willing and able to complete a daily symptom diary for the duration of the study, and comply with the protocol requirements.
  3. Patients must not have had any missing diary entries in the 7 days prior to randomization.
  4. Both male and female patients must agree to practice contraception from the signing of informed consent to 6 months after the last dose of study drugs.

Exclusion Criteria:

  1. Previous treatment with omalizumab within one year prior to signing the informed consent.
  2. Hypersensitivity to omalizumab, study drug excipients or other biosimilars, or have a history of severe drug allergy or anaphylactic shock.
  3. Clearly defined underlying etiology for chronic urticarias other than CSU. This includes but is not limited to:

    1. dermatographism (factitious urticaria);
    2. cold, heat, solar, delayed pressure, aquagenic, cholinergic or contact urticarias;
    3. Any of the following diseases, which may have symptoms of urticaria and/or angioedema: urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, etc.
  4. Patients with a stool examination positive for ova or parasites at screening. {Stool ova and parasite evaluation will only be conducted in patients with BOTH risk factors for parasitic disease (living in an endemic area, and/or chronic gastrointestinal (GI) symptoms and chronic immunosuppression, travel within the last 6 months to an endemic area) AND an absolute eosinophil count more than twice the upper limit of normal.}
  5. Suffer from other chronic pruritic dermatosis that may confound the results: atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.
  6. CSU patients who had difficulty breathing episodes due to angioedema in the past six months.
  7. Active infections requiring treatment at screening, include but not limited to pulmonary infection and tuberculosis.
  8. Patients with platelet count ≤100*109/L at screening.
  9. A history of malignancy of any organ or system within 5 years prior to screening, regardless of local recurrence or metastasis {except for basal cell carcinoma, actinic keratosis, or Bowen's disease (squamous cell carcinoma in situ) that have been treated and have not recurred in the past 12 weeks; Cervical carcinoma in situ or non-invasive malignant colonic polyps that have been resected and have not recurred within the last 5 years}
  10. Presence of clinically significant unstable diseases:

    • High risk of severe ventricular arrhythmias, such as significant left ventricular dysfunction, NYHA class III / IV;
    • Myocardial infarction occurred within 6 months before screening. History of unstable angina, acute coronary syndrome or other high-risk coronary heart disease;
    • Poorly controlled hypertension [Hypertension diagnosis of grade II or III, high risk, and systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg while taking one or two antihypertensive drugs].
  11. Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, hepatic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients, e.g.:

    • Abnormal liver function [AST or ALT ≥ 1.5 x ULN, or total bilirubin ≥ 1.5 x ULN]; abnormal renal function [elevated serum creatinine > 1.5 x ULN];
    • HBsAg positive and HBV DNA quantitative value exceeds the upper limit of the normal value range of each research site, or positive in any one of the tests of hepatitis C virus antibody, HIV antibody and Treponema pallidum antibody;
    • ECG abnormalities of clinical significance, e.g., clinically significant II-III degree atrioventricular (AV) block without a pacemaker, QTc interval≥480 ms, or sustained tachycardia requiring treatment.
  12. History of alcohol or drug abuse, within the last 6 months prior to screening.
  13. Currently participating in other clinical trials, or have received any experimental intervention within 3 months prior to signing the informed consent.
  14. Pregnant or nursing (lactating) women.
  15. Currently taking or plan to take medications prohibited by the protocol at screening.
  16. Other conditions deemed by investigator as unsuitable for this trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    SYN008

    Omalizumab

    Arm Description

    patients received a dose of SYN008 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)

    patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)

    Outcomes

    Primary Outcome Measures

    The change from baseline in the Weekly Itch Severity Score (ISS7) at week 12
    The severity of the itch was recorded by the patient twice daily in their Diary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate)

    Secondary Outcome Measures

    The change from baseline in Urticaria Activity Score Over 7 Days (UAS7) at week 12
    UAS7 is the sum of the NHS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
    The change from baseline in Weekly Number of Hives Score (NHS7) at week 12
    Hives Severity Score (HSS), defined by number of hives, were recorded by the patient once daily in their Diary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 = None = Mild = Moderate = Severe
    Percentage of patients with UAS7≤6
    UAS7 is the sum of the NHS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.
    Correlation analysis between baseline changes of ISS7/UAS7 and baseline IgE level
    The weekly itch severity score is the sum of the daily itch severity scores over 7 days. UAS7 is the sum of the NHS7 and the ISS7 scores.A negative change score from baseline indicates improvement. CSU patients' baseline IgE level correlates with the improvement to a certain extent.
    Time to ISS7 minimal important differences (MID) response
    The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. The time to weekly itch severity score MID response was defined as the time (in weeks) from Day 1 to the study week when weekly itch severity score MID response was first achieved.
    Percentage of patients with ISS7 MID response
    The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. This outcome measure shows the percentage of participants classified as MID Responders at Week 12, meaning their weekly itch severity scores at Week 12 were at least 5 points lower than at Baseline.
    Change from baseline in Overall Dermatology Life Quality Index (DLQI) score
    Dermatology life quality index (DLQI) is a 10-item dermatology- specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.

    Full Information

    First Posted
    June 9, 2021
    Last Updated
    June 22, 2021
    Sponsor
    CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04944602
    Brief Title
    Study to Evaluate the Therapeutic Equivalence of SYN008 Versus Xolair® in the Treatment of Patients With Refractory Chronic Spontaneous Urticaria
    Official Title
    A Multicenter Randomized, Double-blind, Parallel, Positive-controlled Phase III Clinical Trial to Evaluate the Therapeutic Equivalence of SYN008 Versus Xolair® in the Treatment of Patients With Refractory Chronic Spontaneous Urticaria
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    July 2021 (Anticipated)
    Primary Completion Date
    March 2023 (Anticipated)
    Study Completion Date
    June 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    • This study is a multicenter, randomized, double-blind, parallel-group, positive-controlled phase III study to evaluate the therapeutic equivalence of SYN008 versus omalizumab for injection (Xolair®) in the treatment of CSU patients who remain symptomatic despite antihistamine treatment.
    Detailed Description
    A total of approximately 340 patients with H1 antihistamines (H1AH) refractory CSU will be randomized into two treatments arms (SYN008 300 mg s.c., and omalizumab 300 mg s.c.) at a 1:1 ratio. Both SYN008 and omalizumab will be injected every 4 weeks as an add-on therapy on top of H1AH treatment. The study will consist of three distinct epochs over 27 weeks, as follows: Screening epoch: Day -21 to Day -1 Randomized-treatment epoch: Day 1 to Week 12 Post-treatment follow-up epoch: Week 1

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Spontaneous Urticaria

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    340 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    SYN008
    Arm Type
    Experimental
    Arm Description
    patients received a dose of SYN008 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
    Arm Title
    Omalizumab
    Arm Type
    Active Comparator
    Arm Description
    patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
    Intervention Type
    Biological
    Intervention Name(s)
    SYN008
    Intervention Description
    injection of 300 mg
    Intervention Type
    Biological
    Intervention Name(s)
    Omalizumab for injection
    Intervention Description
    injection of 300 mg
    Primary Outcome Measure Information:
    Title
    The change from baseline in the Weekly Itch Severity Score (ISS7) at week 12
    Description
    The severity of the itch was recorded by the patient twice daily in their Diary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate)
    Time Frame
    week 12
    Secondary Outcome Measure Information:
    Title
    The change from baseline in Urticaria Activity Score Over 7 Days (UAS7) at week 12
    Description
    UAS7 is the sum of the NHS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
    Time Frame
    week 12
    Title
    The change from baseline in Weekly Number of Hives Score (NHS7) at week 12
    Description
    Hives Severity Score (HSS), defined by number of hives, were recorded by the patient once daily in their Diary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 = None = Mild = Moderate = Severe
    Time Frame
    week 12
    Title
    Percentage of patients with UAS7≤6
    Description
    UAS7 is the sum of the NHS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.
    Time Frame
    week 12
    Title
    Correlation analysis between baseline changes of ISS7/UAS7 and baseline IgE level
    Description
    The weekly itch severity score is the sum of the daily itch severity scores over 7 days. UAS7 is the sum of the NHS7 and the ISS7 scores.A negative change score from baseline indicates improvement. CSU patients' baseline IgE level correlates with the improvement to a certain extent.
    Time Frame
    week 12
    Title
    Time to ISS7 minimal important differences (MID) response
    Description
    The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. The time to weekly itch severity score MID response was defined as the time (in weeks) from Day 1 to the study week when weekly itch severity score MID response was first achieved.
    Time Frame
    week 12
    Title
    Percentage of patients with ISS7 MID response
    Description
    The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. This outcome measure shows the percentage of participants classified as MID Responders at Week 12, meaning their weekly itch severity scores at Week 12 were at least 5 points lower than at Baseline.
    Time Frame
    week 12
    Title
    Change from baseline in Overall Dermatology Life Quality Index (DLQI) score
    Description
    Dermatology life quality index (DLQI) is a 10-item dermatology- specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.
    Time Frame
    week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of CSU refractory to H1AH at the time of randomization, as defined by all of the following: CSU diagnosis for ≥ 6 months; The presence of itch and hives for ≥ 6 consecutive weeks within one year prior to randomization despite use of H1AH treatment during this time period; UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1); In-clinic UAS ≥ 4 on at least one of the screening visit days; Patients must have been on an approved dose of an H1AH for CSU for at least the 3 consecutive days immediately prior to the screening visit and must have documented current use on the day of the initial screening visit. Voluntarily sign the informed consent form. Willing and able to complete a daily symptom diary for the duration of the study, and comply with the protocol requirements. Patients must not have had any missing diary entries in the 7 days prior to randomization. Both male and female patients must agree to practice contraception from the signing of informed consent to 6 months after the last dose of study drugs. Exclusion Criteria: Previous treatment with omalizumab within one year prior to signing the informed consent. Hypersensitivity to omalizumab, study drug excipients or other biosimilars, or have a history of severe drug allergy or anaphylactic shock. Clearly defined underlying etiology for chronic urticarias other than CSU. This includes but is not limited to: dermatographism (factitious urticaria); cold, heat, solar, delayed pressure, aquagenic, cholinergic or contact urticarias; Any of the following diseases, which may have symptoms of urticaria and/or angioedema: urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, etc. Patients with a stool examination positive for ova or parasites at screening. {Stool ova and parasite evaluation will only be conducted in patients with BOTH risk factors for parasitic disease (living in an endemic area, and/or chronic gastrointestinal (GI) symptoms and chronic immunosuppression, travel within the last 6 months to an endemic area) AND an absolute eosinophil count more than twice the upper limit of normal.} Suffer from other chronic pruritic dermatosis that may confound the results: atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc. CSU patients who had difficulty breathing episodes due to angioedema in the past six months. Active infections requiring treatment at screening, include but not limited to pulmonary infection and tuberculosis. Patients with platelet count ≤100*109/L at screening. A history of malignancy of any organ or system within 5 years prior to screening, regardless of local recurrence or metastasis {except for basal cell carcinoma, actinic keratosis, or Bowen's disease (squamous cell carcinoma in situ) that have been treated and have not recurred in the past 12 weeks; Cervical carcinoma in situ or non-invasive malignant colonic polyps that have been resected and have not recurred within the last 5 years} Presence of clinically significant unstable diseases: High risk of severe ventricular arrhythmias, such as significant left ventricular dysfunction, NYHA class III / IV; Myocardial infarction occurred within 6 months before screening. History of unstable angina, acute coronary syndrome or other high-risk coronary heart disease; Poorly controlled hypertension [Hypertension diagnosis of grade II or III, high risk, and systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg while taking one or two antihypertensive drugs]. Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, hepatic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients, e.g.: Abnormal liver function [AST or ALT ≥ 1.5 x ULN, or total bilirubin ≥ 1.5 x ULN]; abnormal renal function [elevated serum creatinine > 1.5 x ULN]; HBsAg positive and HBV DNA quantitative value exceeds the upper limit of the normal value range of each research site, or positive in any one of the tests of hepatitis C virus antibody, HIV antibody and Treponema pallidum antibody; ECG abnormalities of clinical significance, e.g., clinically significant II-III degree atrioventricular (AV) block without a pacemaker, QTc interval≥480 ms, or sustained tachycardia requiring treatment. History of alcohol or drug abuse, within the last 6 months prior to screening. Currently participating in other clinical trials, or have received any experimental intervention within 3 months prior to signing the informed consent. Pregnant or nursing (lactating) women. Currently taking or plan to take medications prohibited by the protocol at screening. Other conditions deemed by investigator as unsuitable for this trial.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ruo-Yu Li
    Phone
    010-66119025
    Email
    mycolab@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ruo-Yu Li
    Organizational Affiliation
    Peking University First Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Study to Evaluate the Therapeutic Equivalence of SYN008 Versus Xolair® in the Treatment of Patients With Refractory Chronic Spontaneous Urticaria

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