計劃書編號TV45779-IMB-30086
試驗已結束
2021-11-01 - 2025-12-31
Phase III
召募中8
終止收納1
ICD-10L50.1
特發性蕁麻疹
ICD-9708.1
特發性蕁麻疹
A Multinational, Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of TEV-45779 Compared to Omalizumab (XOLAIR®) in Patients With Chronic Idiopathic
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試驗申請者
保瑞爾生技股份有限公司
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試驗委託 / 贊助單位名稱
保瑞爾生技股份有限公司
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臨床試驗規模
多國多中心
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更新日期
2026/04/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 終止收納
適應症
慢性特發性蕁麻疹／慢性自發性蕁麻疹
試驗目的
Primary:
To demonstrate biosimilar efficacy of TEV-45779 300 mg compared to XOLAIR 300 mg as determined by change in itch severity score of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in patients who remain symptomatic despite antihistamine (H1) treatment to demonstrate relative potency of TEV-45779 compared to XOLAIR as determined by itch severity score of CIU/CSU in patients who remain symptomatic despite antihistamine (H1) treatment.
藥品名稱
TEV-45779 (a proposed biosimilar to omalizumab) solution for injection 150 mg/mL (1 mL) prefilled syringe (PFS)
主成份
TEV-45779 (a proposed biosimilar to omalizumab)
劑型
270
劑量
N/A
評估指標
Primary:
• Change from baseline in the weekly itch severity score (ISS7; sum of the daily itch severity score for 7 days) at Week 12, TEV-45779 300 mg compared to XOLAIR 300 mg
• Relative potency of 2 dose levels (300 mg and 150 mg) of TEV-45779 and XOLAIR as measured by ISS7 at Week 12 using a 4 point assay, ie, TEV-45779 300 mg, TEV-45779 150 mg, XOLAIR 300 mg and XOLAIR 150 mg.
Secondary:
Secondary efficacy endpoints are as follows.
• Change from baseline in ISS7 at Week 12
• Change from baseline in the ISS7 at Week 4
• Change from baseline in the weekly urticaria activity score (UAS7; sum of the daily number of wheals score and itch severity score over 7 days) at Week 12
• Percentage of patients with UAS7 ≤6 at Week 12
• Percentage of complete responders (UAS7=0) at Week 12
• Change from baseline in the physician′s (in clinic) assessment of UAS7 at Week 12
• Change from baseline in the weekly number of wheals score at Week 12
• Change from baseline in the weekly size of the largest wheals score at Week 12
• Time to minimally important difference (MID; reduction from baseline in ISS7 of ≥5 points) response up to Week 12
• Percentage of ISS7 MID responders at Week 12 (percentage of
patients with reduction of ≥5 points from baseline in ISS7 at Week 12).
• Percentage of angioedema free days from Week 4 to Week 12
• Change from Week 12 in ISS7 at Week 24
• Change from Week 12 in ISS7 at Week 40
• Change from Week 12 in UAS7 at Week 24
• Change from Week 12 in the physician′s (in clinic) assessment of urticaria activity score (UAS) at 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 40
• Change from Week 12 in the weekly size of the largest wheals score at Week 24
• Change from Week 12 in the weekly size of the largest wheals score at Week 40
• Percentage of angioedema free days from Week 12 to Week 24
The safety/tolerability parameters include:
• Adverse events (and the number of patients who withdraw from the study due to adverse events)
• Change from baseline in clinical laboratory measurements (serum chemistry, hematology, and urinalysis) and vital signs
• Physical examination findings
• Electrocardiogram fndings
• Local tolerability at the injection site after each investigational medicinal product (IMP) administration
• Use of concomitant medication (including use of rescue medication)
• Device-related adverse events and malfunctions
The pharmacokinetic parameter is:
• Omalizumab serum concentration before next dose (Ctrough)
• Omalizumab serum concentration following last dose at Week 24, 28, 32, 36 and 40
The pharmacodynamic parameters are:
• Free immunoglobulin E (IgE) serum concentration
• Total IgE serum concentration
The immunogenicity parameters are:
• Incidence of patients with a confirmed anti drug antibody (ADA) positive sample
• For confirmed positive samples, the ADA titer and the neutralizing potential will be tested
• Change from baseline in the weekly itch severity score (ISS7; sum of the daily itch severity score for 7 days) at Week 12, TEV-45779 300 mg compared to XOLAIR 300 mg
• Relative potency of 2 dose levels (300 mg and 150 mg) of TEV-45779 and XOLAIR as measured by ISS7 at Week 12 using a 4 point assay, ie, TEV-45779 300 mg, TEV-45779 150 mg, XOLAIR 300 mg and XOLAIR 150 mg.
Secondary:
Secondary efficacy endpoints are as follows.
• Change from baseline in ISS7 at Week 12
• Change from baseline in the ISS7 at Week 4
• Change from baseline in the weekly urticaria activity score (UAS7; sum of the daily number of wheals score and itch severity score over 7 days) at Week 12
• Percentage of patients with UAS7 ≤6 at Week 12
• Percentage of complete responders (UAS7=0) at Week 12
• Change from baseline in the physician′s (in clinic) assessment of UAS7 at Week 12
• Change from baseline in the weekly number of wheals score at Week 12
• Change from baseline in the weekly size of the largest wheals score at Week 12
• Time to minimally important difference (MID; reduction from baseline in ISS7 of ≥5 points) response up to Week 12
• Percentage of ISS7 MID responders at Week 12 (percentage of
patients with reduction of ≥5 points from baseline in ISS7 at Week 12).
• Percentage of angioedema free days from Week 4 to Week 12
• Change from Week 12 in ISS7 at Week 24
• Change from Week 12 in ISS7 at Week 40
• Change from Week 12 in UAS7 at Week 24
• Change from Week 12 in the physician′s (in clinic) assessment of urticaria activity score (UAS) at 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 40
• Change from Week 12 in the weekly size of the largest wheals score at Week 24
• Change from Week 12 in the weekly size of the largest wheals score at Week 40
• Percentage of angioedema free days from Week 12 to Week 24
The safety/tolerability parameters include:
• Adverse events (and the number of patients who withdraw from the study due to adverse events)
• Change from baseline in clinical laboratory measurements (serum chemistry, hematology, and urinalysis) and vital signs
• Physical examination findings
• Electrocardiogram fndings
• Local tolerability at the injection site after each investigational medicinal product (IMP) administration
• Use of concomitant medication (including use of rescue medication)
• Device-related adverse events and malfunctions
The pharmacokinetic parameter is:
• Omalizumab serum concentration before next dose (Ctrough)
• Omalizumab serum concentration following last dose at Week 24, 28, 32, 36 and 40
The pharmacodynamic parameters are:
• Free immunoglobulin E (IgE) serum concentration
• Total IgE serum concentration
The immunogenicity parameters are:
• Incidence of patients with a confirmed anti drug antibody (ADA) positive sample
• For confirmed positive samples, the ADA titer and the neutralizing potential will be tested
主要納入條件
Key Inclusion Criteria:
a. Male or female patients aged ≥18 years and ≤75 years.
b. Diagnosis of CIU/CSU refractory to H1 antihistamines at the time of randomization, as defined by all of the following:
- The presence of itch and wheals for ≥8 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine treatment during this time period.
- Weekly urticaria activity score (UAS7; sum of the daily number of wheals score and itch severity score over 7 days) ≥16 (range 0 42) and itch component of UAS7 ≥8 (range 0 21) during 7 days prior to randomization.
- Urticaria activity score (UAS) ≥4 assessed by a clinician on ≥1 of the screening visit days.
- Patients must have been on an approved dose of an H1 antihistamine for CIU/CSU for ≥3 consecutive days immediately prior to the start of screening and must document current use on the day of the initial screening visit.
- CIU/CSU diagnosis for ≥3 months.
c. Women may be included if they fulfill one of the following criteria:
- Women of non-childbearing potential who are either surgically (documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or congenitally sterile as assessed by a physician, or 1 year postmenopausal (no menses for 12 months without an alternative medical cause plus an increased concentration of follicle stimulating hormone [FSH] of more than 35 U/L) in women not using hormonal contraception or hormonal replacement therapy.
- Women of childbearing potential whose male partners are potentially fertile (ie, no vasectomy) must:
- have a negative beta human chorionic gonadotropin (β HCG) test at baseline; result at screening (visit 2); and
- use highly effective birth control methods for the duration of the study (ie, starting at screening) and for 5 half lives (20 weeks) after last dose of IMP.
d. Male patients (including vasectomized) with partners who are of childbearing potential (whether pregnant or not) must use condoms prior to IMP administration and until 20 weeks after last IMP dose.
e. Must be able to understand the requirements of the study and to provide their written informed consent to participate in the study.
f. Must be willing and able to comply with study requirements and procedures as specified in this protocol. In particular, the patient must be willing and able to complete a daily symptom diary for the duration of the study. The patients must not have any missing diary entries in the 7 days prior to randomization.
Key Exclusion Criteria:
a. Body weight <40 kg.
b. Clearly defined underlying etiology for chronic urticarias other than CIU/CSU.
c. Evidence of parasitic infection defined as meeting the following 3 criteria:
- Risk factors for parasitic disease (living in an endemic area, chronic gastrointestinal symptoms, travel within the last 6 months to an endemic area and/or chronic immunosuppression), and
- An absolute eosinophil count more >2× the upper limit of normal (ULN), and
- Evidence of parasitic colonization or infection on stool evaluation for ova and parasites. Note that stool ova and parasite evaluation will only be conducted in patients with risk factor(s) and an eosinophil count >2× the ULN.
d. Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
e. Treatment with an investigational agent within 30 days or longer depending on half life (>5 half lives) prior to the start of screening.
f. Previous treatment with omalizumab within a year prior to the start of screening.
g. Routine (daily or every other day during 5 or more consecutive days) doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
h. Intravenous immunoglobulin G, or plasmapheresis within 30 days prior to the start of screening.
i. Regular (daily/every other day) doxepin (oral) use within 2 weeks prior to the start of screening.
j. Any H2 antihistamine use within 7 days prior to the start of screening.
k. Any LTRA (montelukast or zafirlukast) use within 7 days prior to the start of screening.
l. Any H1 antihistamines at greater than approved doses use within 3 days prior to the start of screening.
m. Current malignancy, history of malignancy, or currently under work up for suspected malignancy except non melanoma skin cancer that has been treated or excised and is considered resolved.
n. Hypersensitivity to omalizumab or any component of the formulation.
o. History of anaphylactic shock.
p. Contraindications to diphenhydramine hydrochloride.
q. Pregnant or lactating woman, or plans to become pregnant during the study.
r. Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
s. Evidence of current drug or alcohol abuse.
t. Patients taking either LTRAs or H2 blockers for diseases other than chronic idiopathic urticaria (CIU) (eg, asthma or gastroesophageal reflux disease, respectively) will be permitted to continue their use during the study. These diseases must be recorded as part of the medical history collected during the screening period. Inhaled asthma controllers, including corticosteroids, are also permitted during the study.
a. Male or female patients aged ≥18 years and ≤75 years.
b. Diagnosis of CIU/CSU refractory to H1 antihistamines at the time of randomization, as defined by all of the following:
- The presence of itch and wheals for ≥8 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine treatment during this time period.
- Weekly urticaria activity score (UAS7; sum of the daily number of wheals score and itch severity score over 7 days) ≥16 (range 0 42) and itch component of UAS7 ≥8 (range 0 21) during 7 days prior to randomization.
- Urticaria activity score (UAS) ≥4 assessed by a clinician on ≥1 of the screening visit days.
- Patients must have been on an approved dose of an H1 antihistamine for CIU/CSU for ≥3 consecutive days immediately prior to the start of screening and must document current use on the day of the initial screening visit.
- CIU/CSU diagnosis for ≥3 months.
c. Women may be included if they fulfill one of the following criteria:
- Women of non-childbearing potential who are either surgically (documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or congenitally sterile as assessed by a physician, or 1 year postmenopausal (no menses for 12 months without an alternative medical cause plus an increased concentration of follicle stimulating hormone [FSH] of more than 35 U/L) in women not using hormonal contraception or hormonal replacement therapy.
- Women of childbearing potential whose male partners are potentially fertile (ie, no vasectomy) must:
- have a negative beta human chorionic gonadotropin (β HCG) test at baseline; result at screening (visit 2); and
- use highly effective birth control methods for the duration of the study (ie, starting at screening) and for 5 half lives (20 weeks) after last dose of IMP.
d. Male patients (including vasectomized) with partners who are of childbearing potential (whether pregnant or not) must use condoms prior to IMP administration and until 20 weeks after last IMP dose.
e. Must be able to understand the requirements of the study and to provide their written informed consent to participate in the study.
f. Must be willing and able to comply with study requirements and procedures as specified in this protocol. In particular, the patient must be willing and able to complete a daily symptom diary for the duration of the study. The patients must not have any missing diary entries in the 7 days prior to randomization.
Key Exclusion Criteria:
a. Body weight <40 kg.
b. Clearly defined underlying etiology for chronic urticarias other than CIU/CSU.
c. Evidence of parasitic infection defined as meeting the following 3 criteria:
- Risk factors for parasitic disease (living in an endemic area, chronic gastrointestinal symptoms, travel within the last 6 months to an endemic area and/or chronic immunosuppression), and
- An absolute eosinophil count more >2× the upper limit of normal (ULN), and
- Evidence of parasitic colonization or infection on stool evaluation for ova and parasites. Note that stool ova and parasite evaluation will only be conducted in patients with risk factor(s) and an eosinophil count >2× the ULN.
d. Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
e. Treatment with an investigational agent within 30 days or longer depending on half life (>5 half lives) prior to the start of screening.
f. Previous treatment with omalizumab within a year prior to the start of screening.
g. Routine (daily or every other day during 5 or more consecutive days) doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
h. Intravenous immunoglobulin G, or plasmapheresis within 30 days prior to the start of screening.
i. Regular (daily/every other day) doxepin (oral) use within 2 weeks prior to the start of screening.
j. Any H2 antihistamine use within 7 days prior to the start of screening.
k. Any LTRA (montelukast or zafirlukast) use within 7 days prior to the start of screening.
l. Any H1 antihistamines at greater than approved doses use within 3 days prior to the start of screening.
m. Current malignancy, history of malignancy, or currently under work up for suspected malignancy except non melanoma skin cancer that has been treated or excised and is considered resolved.
n. Hypersensitivity to omalizumab or any component of the formulation.
o. History of anaphylactic shock.
p. Contraindications to diphenhydramine hydrochloride.
q. Pregnant or lactating woman, or plans to become pregnant during the study.
r. Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
s. Evidence of current drug or alcohol abuse.
t. Patients taking either LTRAs or H2 blockers for diseases other than chronic idiopathic urticaria (CIU) (eg, asthma or gastroesophageal reflux disease, respectively) will be permitted to continue their use during the study. These diseases must be recorded as part of the medical history collected during the screening period. Inhaled asthma controllers, including corticosteroids, are also permitted during the study.
試驗計畫預計收納受試者人數
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台灣人數
100 人
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全球人數
700 人
