A multicenter, randomized, double-blind, placebo controlled Phase 3 study of remibrutinib (LOU064) to investigate the efficacy, safety and tolerability for 52 weeks in adult chronic spontaneous urticaria patients inadequately controlled by H1-antihistamines

JRCT ID: jRCT2031210408

Registered date:02/11/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: chronic spontaneous urticaria
• Date of first enrollment: 01/12/2021
• Target sample size: 22
• Countries of recruitment: Australia,Japan,India,Japan,Korea,Japan,Taiwan,Japan,Turkey,Japan,Argentina,Japan,Colombia,Japan,Mexico,Japan,Bulgaria,Japan,Czech Republic,Japan,France,Japan,Hungary,Japan,Italy,Japan,Portugal,Japan,Russia,Japan,Spain,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug A: LOU064 (blinded)
Drug B: Placebo
Drug C: LOU064 (open-label)

Outcome(s)

Primary Outcome

Change from baseline in UAS7 (Scenario 1 with UAS7 as primary efficacy endpoint) [ Time Frame: 12 weeks ]
To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 by assessing absolute change from baseline in weekly Urticaria Activity Score (UAS7) at week 12.

The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.

Absolute change in ISS7 and absolute change in HSS7 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints) [ Time Frame: 12 weeks ]
To demonstrate that remibrutinib is superior to placebo in CSU with respect to change from baseline in ISS7 and HSS7 at Week 12 by assessing absolute change from baseline in weekly Itch Severity Score (ISS7) and weekly Hive Severity Score (HSS7) at week 12.

The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The HSS7 score is the wheal/hives severity score for 7 days and the ISS7 is the itch severity score for 7 days, both these scores range from 0 to 21.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Signed informed consent must be obtained prior to participation in the study.
- Male and female adult participants =>18 years of age.
- 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 antihistamines at the time of randomization defined as:
- The presence of itch and hives for =>6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines during this time period
- UAS7 score (range 0-42) =>16, ISS7 score (range 0-21) =>6 and HSS7 score (range 0-21) => during the 7 days prior to randomization (Day 1)
- Documentation of hives within three months before randomization (either at screening and/or at randomization; 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 one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).

Exclude criteria

- 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 contact-urticaria
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, 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
- 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 uncontrolled 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, e.g. in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiring hospitalization or blood transfusion)
- Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is prohibited.
- 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

Related Information

• Primary Sponsor: Yamada Hiroyuki
• Secondary ID(s): NCT05030311