24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

JRCT ID: jRCT2031230679

Registered date:06/03/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Chronic Spontaneous Urticaria
• Date of first enrollment: 27/03/2024
• Target sample size: 8
• Countries of recruitment: Argentina,Japan,Canada,Japan,Chile,Japan,China,Japan,Germany,Japan,Hong Kong,Japan,Italy,Japan,Malaysia,Japan,Netherlands,Japan,Poland,Japan,Singapore,Japan,South Africa,Japan,Spain,Japan,Thailand,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: Arm 1: LOU064 (blinded)
-LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 6 cycles of 24 weeks.
-Interventions:
Drug: LOU064 (blinded)
Placebo Comparator: Arm 2: LOU064 placebo (blinded)
-LOU064 placebo (blinded) taken orally b.i.d. for 24 weeks (randomized in a 2:1 ratio arm 1: arm 2) .
-Interventions:
Drug: placebo

Outcome(s)

Primary Outcome

Change from baseline in UAS7 [Time Frame: Baseline, week 12]
-The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0.
-Negative change from baseline indicates improvement.

Change fron baseline in ISS7 [Time Frame: Baseline, Week 12]
-Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate).
-Negative change from baseline indicates improvement.

Change from baseline in HSS7 [Time Frame: Baseline, Week 12]
-Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours).
-Negative change from baseline indicates improvement.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: < 18age old
• Gender: Both

Include criteria

Male and female adolescent participants aged >= 12 to < 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 randomization 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 according to local treatment guidelines
-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 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)

Exclude criteria

Previous use of remibrutinib or other BTK inhibitors
Significant bleeding risk or coagulation disorders.
History of gastrointestinal bleeding.
Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
History or current hepatic disease.
Evidence of clinically significant cardiovascular, 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.
History of hypersensitivity to any of the study drugs 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 contact-urticaria
Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria 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

Related Information

• Primary Sponsor: Iwasaki Ryohei
• Secondary ID(s): NCT05677451