| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Spontaneous Urticaria |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hives that are present for at least or greater than 6 weeks and for the most days of the week. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10072757 |
| E.1.2 | Term | Chronic spontaneous urticaria |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate the equivalence of CT P39 to Xolair at a dose of 300 mg in terms of efficacy in patients with chronic spontaneous urticaria (CSU) as determined by change from baseline in weekly itch severity score (ISS7) at Week 12 |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate relative potency and dose response in terms of efficacy between 300 mg and 150 mg for CT P39 and Xolair
• To evaluate additional efficacy of CT P39 and Xolair at each dose level of 300 mg and 150 mg
• To evaluate the pharmacokinetics (PK), quality of life (QoL), safety, and immunogenicity of CT P39 and Xolair |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each patient must meet all of the following criteria to be randomized in this study:
1. Male or female between 12 and 75 years of age (both inclusive; age limits would depend on country specific regulation).
2. Have been diagnosed with CSU for at least 6 months prior to the first study drug administration.
3. Must be diagnosed as CSU refractory to H1-antihistamine defined as below:
a) Presence of hives associated with itching for ≥ 6 consecutive weeks at any time prior to the first study drug administration despite current use of H1-antihistamine treatment for this time period
b) Weekly itch severity score (range 0 to 21 points) ≥ 8 points and weekly urticaria activity score (UAS7; range 0 to 42 points) ≥ 16 points in the 7 consecutive days (Day -7 to Day -1) prior to the first study drug administration
c) Documented use of an approved dosage of nonsedating H1-antihistamine for CSU for at least 3 consecutive days immediately prior to start of patient electronic diary (eDiary) record for baseline ISS7 (Day - 7 to Day - 1)
4. Has patient eDiary entries without missing data in the 7 consecutive days (Day -7 to Day -1) prior to the first study drug administration.
5. Be willing and able to complete a patient eDiary twice daily (morning and evening) throughout the study.
6. Patient and/or their legally authorized representative are informed and will be given ample time and opportunity to read and/or understand the nature and purpose of this study including possible risks and side effects and must sign the informed consent form before any specific procedures.
7. Female patient must agree to use highly effective methods of contraception consistent with local regulations throughout the study period (excluding women who are not of childbearing potential). Examples include the following:
a) Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives associated with inhibition of ovulation
b) Intrauterine device or intrauterine hormone-releasing system
c) True abstinence, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational drug, and withdrawal are not acceptable methods of contraception.
Menopausal female patients must have experienced their last period more than 1 year prior to the date of informed consent to be classified as not of childbearing potential. Male patient who is sexually active with a woman of childbearing potential must agree to use highly effective method described as above or two acceptable methods of contraception (e.g., male or female condom AND additional hormonal or barrier contraceptive method other than condom by female partner) consistent with local regulations throughout the study period. Contraception is not required if either patient or his/her partner who has been surgically sterilized more than 24 weeks prior to the date of informed consent. |
|
| E.4 | Principal exclusion criteria |
A patient meeting any of the following criteria will be excluded from the study:
1. Has a chronic urticaria with clearly defined underlying etiology (e.g., physical urticaria such as acute, solar, cholinergic, heat, cold, aquagenic, pressure or contact) other than CSU or any disease with symptoms of urticaria or angioedema (e.g., urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia or generalized cancer).
2. Has a body weight of < 30 kg.
3. Has a medical history of and/or current disease including any of the following:
a) History of clinically significant allergic reaction and/or hypersensitivity to any component of omalizumab, Chinese hamster ovary cell products, other recombinant human or humanized antibodies, H1-antihistamines, or dry natural rubber (a derivative of latex)
b) History of and/or concomitant myocardial infarction
c) History of anaphylactic shock
d) History of and/or concomitant immune complex disease (including allergic reaction type III), hyperimmunoglobulin E syndrome, autoimmune disease, or bronchopulmonary aspergillosis
e) Any active skin disease associated with itch including atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, or senile pruritus
f) A known infection with human immunodeficiency virus, hepatitis B, hepatitis C, or any active infection requiring treatment, except adequately treated and completely recovered past infections
g) Any active malignancy or history of malignancy except adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ
4. Has history of and/or a current use of medications including any of the following:
a) Treatment with omalizumab or other monoclonal antibodies, protein, fusion protein, or other biologic agent targeting immunoglobulin E (IgE)
b) Treatment with an investigational drug within 4 weeks or 5 half-lives (whichever is longer) prior to the first study drug administration
c) Routine administration (i.e., daily or every other day for ≥ 5 consecutive days) of systemic glucocorticoids, hydroxychloroquine, methotrexate, cyclosporine, azathioprine, cyclophosphamide, tacrolimus, or mycophenolate mofetil within 5 weeks prior to the first study drug administration
d) Intravenous immunoglobulin G or plasmapheresis within 5 weeks prior to the first study drug administration
e) Regular (i.e., daily or every other day for ≥ 5 consecutive days) use of oral doxepin within 3 weeks prior to the first study drug administration
f) Use of any H2-antihistamine or leukotriene receptor antagonist within 2 weeks prior to the first study drug administration (However, continuing H2-antihistamine or leukotriene receptor antagonist treatment for disease other than CSU is allowed)
g) Use of beta-blocker therapy within 2 weeks prior to the first study drug administration
h) Use of H1-antihistamines at greater than approved doses from 3 days prior to the start of patient eDiary record for baseline ISS7 (Day - 7 to Day - 1)
5. Diagnosed with parasitic diseases or colonization on stool evaluation for ova and parasites (stool ova and parasite examination should be performed in patients who meet both the following criteria):
a) Correspond to any of risk factors for parasitic disease
• Travel within 6 months prior to the first study drug administration or living in an endemic area of parasitic infections
• Chronic gastrointestinal symptoms
• Chronic immunosuppression
b) Absolute eosinophil count > 2 × upper limit of normal
6. Unable to receive background therapy and rescue therapy with protocol-defined H1-antihistamines or contraindicated to epinephrine or other components of these agents as per Investigator’s discretion.
7. Has ongoing or a history of alcohol or drug abuse within 6 months prior to the first study drug administration.
8. Female patient who is currently pregnant or breastfeeding, or plans to become pregnant or breastfeed, or male patient who is planning to father a child or donate sperm during study period.
9. Has evidence of any other coexisting disease or medical or psychological condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational product or could interfere with the interpretation of study results, or patient is at high risk for treatment complication in the opinion of the Investigator.
10. Vulnerable patients (e.g., employees of the clinical study center or any other individuals involved with the conduct of the study, or immediate family members of such individuals, persons kept in prison or other persons institutionalized by law enforcement). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the change from baseline in ISS7 of 300 mg of CT-P39 (Arm 1) and 300 mg of Xolair (Arm 2) at Week 12. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline in ISS7 at Weeks 8 and 24
• Time to minimally important difference (MID; reduction of ≥ 5 points from baseline) response in ISS7 by Week 12
• Percentage of MID responders in ISS7 at Weeks 8, 12, and 24
• Relative potency of CT-P39 compared with Xolair as determined by change from baseline in ISS7 at Week 12
• Change from baseline in UAS7 at Weeks 8, 12, and 24
• Percentage of patients with UAS7 of ≤ 6 points at Weeks 8, 12, and 24
• Percentage of complete responders (UAS7 = 0) in UAS7 at Weeks 8, 12, and 24
• Change from baseline in the weekly hives severity score at Weeks 8, 12, and 24
• Percentage of angioedema-free days from Weeks 4 to 12
• Change from baseline in number of tablets/week of rescue therapy at
Week 8, 12, and 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Korea, Republic of |
| Poland |
| Bulgaria |
| Greece |
| Hungary |
| Russian Federation |
| Ukraine |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 28 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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