An Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Subjects With CSU

Chronic Spontaneous Urticaria Clinical Trial

Official title:

An Open-label, Multicenter, Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Eligible Subjects With CSU Who Have Participated in CLOU064A2201

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04109313
• Other study ID #: CLOU064A2201E1
• Secondary ID: 2019-001074-29
• Status: Completed
• Phase: Phase 2
• Start date: October 24, 2019
• Est. completion date: September 9, 2022

Study information

• Verified date: September 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective to assess the long-term safety and tolerability of LOU064 in patients with chronic spontaneous urticaria (CSU) who have participated in study CLOU064A2201 (NCT03926611)

Description:

This was an open-label, single-arm, multicenter, long-term safety and tolerability extension study for CSU patients rolling over from study CLOU064A2201 (NCT03926611). Subjects rolling over from CLOU064A2201 with a weekly Urticaria Activity Score (UAS7)<16 after the follow-up period at Week 16 were further followed up without receiving LOU064 for up to 12 weeks (observational period). If there was a relapse (UAS7≥16 at least once), the 12-week observational period was terminated, and subjects entered the treatment period. Subjects who never relapsed within 12 weeks completed the study after the observational period without treatment. Subjects who rolled over from CLOU064A2201 with a UAS7≥16 at Week 12 or Week 16, as well as those subjects who relapsed during the 12-week observational period, were treated with 100 mg LOU064 twice a day (b.i.d.) open-label for 52 weeks. No background medication with a second-generation H1-antihistamine was permitted up to Week 4 of the treatment period. Subjects who completed the treatment period or who discontinued treatment early were followed-up for a minimum duration of 4 weeks. Subjects who had a UAS7≤6 at Week 52 of the treatment period had their follow-up period extended until relapse (UAS7≥16) for up to a total of 16 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 229
• Est. completion date: September 9, 2022
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Key Inclusion Criteria:

• Participants must provide written informed consent prior to any assessments.
• Participants must be willing and able to complete a daily symptom eDiary throughout the study and adhere to the study visit schedules.
• Participants transitioning from the CLOU064A2201 trial must have completed either the Week 12 visit (end of treatment period) or the Week 16 visit (end of follow-up period). They will be assigned to either the treatment period or the observational period based on their UAS7 score (average score from the 7 days prior to the

respective visit) as follows:

1. Participants transitioning at Week 12 of CLOU064A2201 with a UAS7 score of =16 will be allocated to the treatment period.

2. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of =16 will be allocated to the treatment period.

3. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of <16 will be allocated to the observational period.

Key Exclusion Criteria:

• Participants with a clearly defined predominant or sole trigger for their chronic urticaria, such as chronic inducible urticaria (including symptomatic dermographism, cold-induced, heat-induced, solar-induced, pressure-induced, delayed pressure-induced, aquagenic-induced, cholinergic-induced, or contact-induced urticaria).
• Participants with other diseases presenting with urticaria or angioedema symptoms, including but not limited to urticaria vasculitis, urticarial pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or acquired/drug-induced urticaria.
• Participants with any other skin disease associated with chronic itching that, in the opinion of the investigator, could affect the study evaluations and results, such as atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis.
• Participants with a history or current diagnosis of ECG abnormalities that indicate a

significant safety risk for their participation in the study, including:

• Concomitant clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia) and clinically significant second or third-degree AV block without a pacemaker.
• History of familiar long QT syndrome or a known family history of Torsades de Pointes.
• Resting heart rate (as determined by physical exam or 12-lead ECG) below 50 bpm.
• Resting QTcF interval =450 msec (in males) or =460 msec (in females) at day 1 of the treatment period or inability to determine the QTcF interval.
• Use of agents known to prolong the QT interval, unless they can be permanently discontinued for the duration of the study.
• Participants with a significant risk of bleeding or coagulation disorders.
• Participants with a known or suspected history of an ongoing, chronic, or recurrent infectious disease, including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis, or aspergillosis), HIV, or Hepatitis B/C.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• LOU064
Participants with a UAS7=16 at Week 12 or Week 16 in the CLOU064A2201, as well as participants who experienced a relapse during the 12-week observational period, were administered LOU064 50mg capsules b.i.d. (i.e. two capsules of LOU064 50mg in the morning and two capsules of LOU064 50mg in the evening) from Day 1 up to Week 52 of the Treatment period.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad de Mendoza	Mendoza
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Liege
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Niagara Falls	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Verdun	Quebec
Czechia	Novartis Investigative Site	Prague	Prague 1
Czechia	Novartis Investigative Site	Prague 8	Czech Republic
Czechia	Novartis Investigative Site	Tabor
Denmark	Novartis Investigative Site	Arhus C
Denmark	Novartis Investigative Site	Copenhagen NV
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice Cedex
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Oroshaza	Bekes
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szolnok
Japan	Novartis Investigative Site	Funabashi	Chiba
Japan	Novartis Investigative Site	Hiroshima City	Hiroshima
Japan	Novartis Investigative Site	Ichinomiya	Aichi
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Takaoka	Toyama
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St.-Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Svidnik
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Turkey	Novartis Investigative Site	Denizli
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Talas / Kayseri
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Plymouth
United States	Novartis Investigative Site	Grove City	Ohio
United States	Novartis Investigative Site	Litchfield Park	Arizona
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Mission Viejo	California
United States	Novartis Investigative Site	Owensboro	Kentucky
United States	Novartis Investigative Site	Pembroke Pines	Florida
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Walnut Creek	California
United States	Novartis Investigative Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Czechia,  Denmark,  France,  Hungary,  Japan,  Poland,  Russian Federation,  Slovakia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (AEs)	An AE refers to any undesirable medical occurrence, such as an unintended sign (including abnormal laboratory findings), symptom, or disease, experienced by a participant. Serious AEs (SAEs) is defined as any AE that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or any other medically significant condition.; Treatment-emergent AEs were defined as AEs that either begin on the same day or after the first dose of study medication during the treatment period in the extension study or worsen on the same day or after the first dose of study medication in the extension study and within the minimum of either 28 days post last dose or the end of the study visit. The number of participants with treatment-emergent AEs was summarized.	From first dose of treatment up to 28 days after last dose, assessed up to 56 weeks
Secondary	Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 of the Treatment Period	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The change from baseline in UAS7 at Week 4 of the treatment period was calculated. A negative change score from baseline indicates improvement. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	Baseline, Week 4 of treatment period
Secondary	Percentage of Participants With Well-controlled Disease (UAS7=6) at Week 4 of the Treatment Period	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. Missing values were imputed by non-responder imputation method regardless of the reason for missingness.; The percentage of subjects with UAS7= 6 at Week 4 of the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction.	Week 4 of the treatment period
Secondary	Percentage of Participants With Complete Response (UAS7=0) at Week 4 of the Treatment Period	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. Missing values were imputed by non-responder imputation method regardless of the reason for missingness.; The percentage of subjects with UAS7= 0 at Week 4 of the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction.	Week 4 of the treatment period
Secondary	Percentage of Participants With Well-controlled Disease (UAS7= 6) Overtime	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The percentage of subjects with UAS7= 6 during the treatment period was calculated. The 90% confidence interval was derived based on the score method with continuity correction. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	From baseline until Week 52 of the treatment period
Secondary	Change From Baseline in UAS7 Overtime	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The change from baseline in UAS7 during the treatment period was calculated. A negative change score from baseline indicates improvement. The UAS7 at baseline was considered as the UAS7 derived over the last 7 days before day 1 of the treatment period.	From baseline until Week 52 of the treatment period