This Was a Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo- Controlled Phase 2b Dose-finding Study to Investigate the Efficacy, Safety and Tolerability of LOU064 in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03926611
• Other study ID #: CLOU064A2201
• Secondary ID: 2018-000993-31
• Status: Completed
• Phase: Phase 2
• Start date: June 6, 2019
• Est. completion date: April 15, 2021

Study information

• Verified date: April 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a multicenter, randomized, double-blind and placebo-controlled phase 2b dose-finding study to assess the efficacy and safety of LOU064 in adults chronic spontaneous urticaria (CSU) patients inadequately controlled by H1-antihistamines

Description:

This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebo-controlled study investigating the efficacy, safety and tolerability of six dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. The study comprised of the 7 treatment arms: LOU064 10 mg q.d., LOU064 35 mg q.d., LOU064 100 mg q.d., LOU064 10 mg b.i.d, LOU064 25 mg b.i.d., LOU064 100 mg b.i.d. and placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 311
• Est. completion date: April 15, 2021
• Est. primary completion date: January 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Male and female subjects aged =18 years of age

• CSU diagnosis for = 6 months prior to screening

• Presence of itch and hives for =6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local Treatment guidelines during this time period

• UAS7 score (range 0-42) =16 and HSS7 score (range 0-21) = 8 during 7 days prior to randomization (Day 1)

• Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study

Exclusion Criteria:

• Hypersensitivity to any of the study treatments

• Clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria)

• Other diseases with symptoms of urticaria or angioedema

• Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results,

• Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C.

• Pregnant or nursing (lactating) women

• Women of child-bearing potential not using highly effective methods of contraception

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• LOU064 Arm 1
10 mg LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
• LOU064 Arm 2
35 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
• LOU064 Arm 3
100 mg of LOU064 orally in the morning (once daily) and matching placebo in the evening from Day 1 to 85
• LOU064 Arm 4
10mg bid of LOU064 orally, twice daily from Day 1 to 85
• LOU064 Arm 5
25 mg bid of LOU064 orally, twice daily from Day 1 to 85
• LOU064 Arm 6
100 mg bid of LOU064 orally, twice daily from Day 1 to 85
• Placebo arm
Matching placebo, orally, twice daily from Day 1 to 85

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
France	Novartis Investigative Site	Pierre Benite Cedex
France	Novartis Investigative Site	Rouen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Muenchen
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Debrecen	Hajdu Bihar
Hungary	Novartis Investigative Site	Oroshaza
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	Koto	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
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Utrecht
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
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	St 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	Westminster	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,  Germany,  Hungary,  Japan,  Netherlands,  Poland,  Russian Federation,  Slovakia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4	UAS7 score change (LS mean Change) from baseline at Week 4 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS); 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. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (week 4 score minus Baseline score) indicates improvement.	Baseline, Week 4
Secondary	Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12	UAS7 score change (LS mean Change) from baseline at Week 12 estimated with a mixed-effect repeated measurement analysis of UAS7 score change from baseline (FAS)	Week 12
Secondary	Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6)	UAS7=0 and UAS7<=6 response rate over time by treatment group (non-responder imputation) 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. The maximum UAS7 value is 42. A higher score indicates more severe disease. A negative change score (week 4 score minus Baseline score) indicates improvement.	Week 12
Secondary	Cumulative Number of Weeks With an AAS7=0 Response	The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reports the occurrence of angioedema ("opening question") with "no", AAS score for this day is 0. If "yes" is the answer to the opening question, the subject will continue to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. Higher score means more severe disease.	Baseline to Week 12
Secondary	Percentage of Participants With DLQI Score of 0 or 1	Percentage of subjects with DLQI 0/1 response by treatment group and visit (non-responder imputation); The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). A DLQI score of 0 or 1 means that there is no impact of a skin disease on the patient's life.	Week 4 and Week 12
Secondary	Mean Change From Baseline in DLQI Score	Summary of DLQI score and change from baseline; The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL).	Baseline, Week 4 and Week 12
Secondary	Area Under the Blood Concentration-time Curve (AUC) of LOU064	Assessment of the area under the blood concentration-time curve (AUC) up to four hours following oral administration at Week 4 and Week 12 .	Week 4 and Week 12
Secondary	Observed Maximum Blood Concentration (Cmax) of LOU064	Assessment of the observed maximum blood concentration (Cmax) of LOU064 following drug administration at Week 4 and Week 12 .	Week 4 and Week 12
Secondary	Time to Reach the Maximum Concentration (Tmax) of LOU064	Assessment of the time to reach the maximum concentration (Tmax) of LOU064 following drug administration at Weeks 4 and 12	Week 4 and Week 12

External Links

•   A Plain Language Trial Summary is available on novctrd.com