E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
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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 rule out an increase of >3mmHg in 24-hour average SBP at steady state (Week 4) compared to baseline, measured by ambulatory blood pressure monitoring (ABPM). |
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E.2.2 | Secondary objectives of the trial |
- To evaluate changes in 24-hour average SBP at steady state (Week 4) compared to baseline - To evaluate changes in 24-hour average DBP at steady state (Week 4) compared to baseline - To evaluate changes in daytime and nighttime average SBP at 4 weeks - To evaluate changes in daytime and nighttime average DBP at 4 weeks - To evaluate the safety and tolerability of remibrutinib |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
DNA sampling / Pharmacogenetics: The study includes an optional genetic research component. The purpose of genetic research may be to better understand the safety and efficacy of remibrutinib, or to learn more about human diseases, or to help develop ways to detect, monitor and treat diseases. As technology changes over time, the most appropriate technology will be used at the time the exploratory genetic research is performed. This may include the study of the entire genome. The use of DNA to search for biomarkers of disease and drug action is exploratory. |
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E.3 | Principal inclusion criteria |
- Signed informed consent must be obtained prior to participation in the study. - Male and female adult participants ≥18 years of age at the time of screening. - CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation). - Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of baseline (Day 1) defined as: -- The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of second generation H1-AH during this time period. -- UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-21) ≥ 6 during the 7 days prior to baseline (Day 1). - Documentation of hives within three months before baseline (either at screening and/or at baseline (Day 1); or documented in the participants` medical history). - Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. - Participants must not have had more than two missing UPDD entry (either morning or evening) in the 7 days prior to baseline (Day 1). |
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E.4 | Principal exclusion criteria |
- Use of other investigational drugs within 5 half-lives or within 30 days (for small molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations. - Previous use of remibrutinib or other BTK inhibitors. - History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes. - Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contacturticaria. - Ongoing or past history of hypertension and/or SBP ≥140 or ≤90 and/or DBP ≥90 or ≤60 mmHg at screening. - Participants unable to tolerate 24-hour ambulatory blood pressure measurement prior to baseline. - Participants with an arm circumference greater than 50cm. - Other diseases with symptoms of urticaria or angioedema, including but not limited to urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria. - Any other skin disease associated with chronic itching that might influence, in the investigator’s opinion, the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis. - Participants taking/requiring medications prohibited by the protocol - Known history or evidence of ongoing alcohol or drug abuse within the last 6 months before baseline (Day 1). - Participants working night shifts. - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. - Pregnant or nursing (lactating) women. - Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and ongoing hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant. Significant bleeding risk or coagulation disorders. - History of gastrointestinal bleeding. - Requirement for antiplatelet medication. The use of acetylsalicylic acid (up to 100mg/day) or clopidogrel (up to 75mg/day) is allowed after the completion of Week 4 visit. - Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)). - History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening.
Other protocol-defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in the ABPM-measured 24-hour weighted average SBP at Week 4 compared to baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The change in the ABPM-measured 24-hour weighted average SBP at Week 4 compared to baseline 2. the change in the measured ABPM 24-hour weighted average DBP at Week 4 compared to baseline 3. the change in the measured ABPM daytime and nighttime weighted average SBP at Week 4 4. the change in the measured ABPM daytime and nighttime weighted average DBP at Week 4 5. Occurrence of treatment emergent adverse events and serious adverse events (SAEs) during the study, evaluation of laboratory and vital signs data |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Week 4 Endpoint #5: End of study |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Argentina |
Singapore |
Canada |
Korea, Republic of |
Turkey |
United States |
France |
Germany |
Slovakia |
Spain |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |