An Extension Study of Long-term Efficacy, Safety and Tolerability of Remibrutinib in Chronic Spontaneous Urticaria Patients Who Completed Preceding Studies With Remibrutinib

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal and Open-label Extension Study Followed by Long-term Open-label Treatment Cycles to Assess the Efficacy, Safety and Tolerability of Remibrutinib (LOU064) in Adult Chronic Spontaneous Urticaria Patients Who Completed the Preceding Remibrutinib Phase 3 Studies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05513001
• Other study ID #: CLOU064A2303B
• Secondary ID: 2022-001034-11
• Status: Recruiting
• Phase: Phase 3
• Start date: December 9, 2022
• Est. completion date: August 10, 2027

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this extension study is to collect long-term efficacy, safety and tolerability data on remibrutinib in a selected group of participants with Chronic Spontaneous Urticaria (CSU) who previously completed the treatment phase of remibrutinib preceding Phase 3 studies. This study will also fulfill the Novartis commitment to provide post-trial access to participants who have completed the preceding Phase 3 studies, where applicable.

Description:

This is a global, multicenter, randomized, double-blind, placebo-controlled, randomized withdrawal Phase 3b extension study, followed by long-term open label treatment cycles to assess the efficacy, safety and tolerability of remibrutinib in adult participants with CSU inadequately controlled by H1-AH. The study comprises 2 Epochs. Epoch 1 is the initial study period for participants who completed preceding remibrutinib Phase 3 studies. Epoch 1 comprises of a 24-week randomized withdrawal period with remibrutinib or placebo for patients with UAS7<16 OR a 24 week Open-label treatment period with remibrutinib for patients with UAS7≥16. Participants will be randomized in a 1:1 ratio to enter the double-blind placebo-controlled 24-week withdrawal phase. In case of relapse (UAS7≥16) in the blinded group, participants enter the (Re-)treatment period Epoch 1 and receive 24 weeks of Open-label treatment with remibrutinib. At the end of the (Re-)treatment period Epoch 1, participants will move to Epoch 2. Epoch 2 is the second subsequent study period and consists of 24-week cycles that could either encompass treatment-free Observation and/or Open-label (Re-)treatment periods with remibrutinib, with or without background H1-AH. In case of relapse (UAS7≥16) during an Observation period, participants enter the next (Re-)treatment period and receive 24 weeks of treatment with remibrutinib. Participants completing an Observation period 2/3/4/5 with a UAS7≤6 will complete the study. Participants with a UAS7 >6 -<16 can enter the next (Re-)treatment period if continuous treatment is considered necessary and beneficial for the individual participant. For participants with a UAS7<16 that enter the next (Re-)treatment period, remibrutinib monotherapy treatment (without background H1-AH) is required.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1021
• Est. completion date: August 10, 2027
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Male and female, adult participants =18 years of age.
• Participants who successfully completed the preceding core studies CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 or CLOU064A2305 according to the respective protocols.
• Willing and able to adhere to the study protocol and visit schedule.

Exclusion Criteria:

• Significant bleeding risk or coagulation disorders.
• History of gastrointestinal bleeding.
• Requirement for anti-platelet medication.
• Requirement for anticoagulant medication.
• 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.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• LOU064 (blinded)
LOU064 (blinded) active treatment
• Placebo
Placebo
• LOU064 (open label)
LOU064 (open-label) active treatment

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bahia Blanca
Argentina	Novartis Investigative Site	Buenos Aires	Nueve De Julio
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Ranelagh Partido De Berazate	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Australia	Novartis Investigative Site	East Melbourne	Victoria
Australia	Novartis Investigative Site	Parkville	Victoria
Brazil	Novartis Investigative Site	Santo Andre	SP
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Fredericton	New Brunswick
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Niagara Falls	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Verdun	Quebec
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangdong	Guangzhou
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuxi	Jiangsu
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Medellin	Antioquia
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Olomouc
Czechia	Novartis Investigative Site	Plzen
Czechia	Novartis Investigative Site	Praha 5
Denmark	Novartis Investigative Site	Copenhagen NV
Denmark	Novartis Investigative Site	Hellerup
France	Novartis Investigative Site	Angers 09
France	Novartis Investigative Site	Antony
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Saint Mande
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bramsche
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Halle (Saale)
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Langenau
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Merzig
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Hungary	Novartis Investigative Site	Debrecen	Hajdu Bihar
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	Belagavi	Karnataka
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Izumiotsu	Osaka
Japan	Novartis Investigative Site	Izumo-city	Shimane
Japan	Novartis Investigative Site	Kamimashi-gun	Kumamoto
Japan	Novartis Investigative Site	Koto	Tokyo
Japan	Novartis Investigative Site	Minato	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Neyagawa	Osaka
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Takatsuki	Osaka
Japan	Novartis Investigative Site	Takatsuki-city	Osaka
Japan	Novartis Investigative Site	Urayasu	Chiba
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Korea, Republic of	Novartis Investigative Site	Daegu	Dalseo Gu
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Hwaseong si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Suwon si	Gyeonggi Do
Malaysia	Novartis Investigative Site	Ipoh	Perak
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Muar	Johor
Malaysia	Novartis Investigative Site	Penang
Malaysia	Novartis Investigative Site	Wilayah Persekutuan
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Puerto Rico	Alma Cruz-Santana Private Practice	Carolina
Russian Federation	Novartis Investigative Site	Izhevsk
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Kezmarok
Slovakia	Novartis Investigative Site	Komarno
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Levice
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Svidnik
South Africa	Novartis Investigative Site	Cape Town	Western Province
South Africa	Novartis Investigative Site	Pretoria	Gauteng
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Zuerich
Switzerland	Novartis Investigative Site	Zuerich
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok	Phayathai
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kayseri
Turkey	Novartis Investigative Site	Sakarya
Turkey	Novartis Investigative Site	Samsun
Turkey	Novartis Investigative Site	Talas / Kayseri
United Kingdom	Novartis Investigative Site	Cardiff
United States	Oakview Dermatology	Athens	Ohio
United States	Orion Clinical Research .	Austin	Texas
United States	Florida Ctr Allergy Asthma Research	Aventura	Florida
United States	Florida Ctr Allergy Asthma Research .	Aventura	Florida
United States	Kern Research	Bakersfield	California
United States	John Hopkins University	Baltimore	Maryland
United States	Bellingham Asthma Allergy and Immunology	Bellingham	Washington
United States	Allervie Clinical Research	Birmingham	Alabama
United States	Cahaba Derm and skin hlth ctr 27	Birmingham	Alabama
United States	Treasure Valley Medical Research	Boise	Idaho
United States	Institute for Asthma and Allergy PC	Chevy Chase	Maryland
United States	Asthma and Allergy Associates P C	Colorado Springs	Colorado
United States	Optimed Research LLC	Columbus	Ohio
United States	Colorado Allergy and Asthma Ctr PC .	Denver	Colorado
United States	CR Services Acquisition US	Dublin	Ohio
United States	Western Sky Medical Research	El Paso	Texas
United States	Deaconess Clin Allerg Res Inst	Evansville	Indiana
United States	UCONN Health Dermatology	Farmington	Connecticut
United States	Northshore University Health System	Glenview	Illinois
United States	Finlay Medical Research	Greenacres City	Florida
United States	Allergy Asthma and amp Sinus Center S C	Greenfield	Wisconsin
United States	Antelope Valley Clinical Trials	Lancaster	California
United States	Somnos Clinical Research .	Lincoln	Nebraska
United States	Research Solutions of Arizona .	Litchfield Park	Arizona
United States	Little Rock Allergy and Asthma Clnc	Little Rock	Arkansas
United States	Allergy Asthma Assoc Monmouth	Little Silver	New Jersey
United States	Miami Dade Medical Research	Miami	Florida
United States	Allergy Associates of Utah	Murray	Utah
United States	National Allergy and Asthma Research LLS	North Charleston	South Carolina
United States	Arkansas Research Trials	North Little Rock	Arkansas
United States	Allergy Asthma and Clinical Research	Oklahoma City	Oklahoma
United States	Allergy and Asthma Specialist P S C	Owensboro	Kentucky
United States	Allergy and Clinical Immunology Ass	Pittsburgh	Pennsylvania
United States	The Indiana Clinical Trials Center	Plainfield	Indiana
United States	Allergy and Asthma Consultants	Redwood City	California
United States	Asthma and Allergy Center of Chicago S C	River Forest	Illinois
United States	The Clinical Research Center .	Saint Louis	Missouri
United States	RFSA Dermatology	San Antonio	Texas
United States	Sarasota Clinical Research .	Sarasota	Florida
United States	AeroAllergy Research Laboratories of Savannah, Inc.	Savannah	Georgia
United States	Seattle Allergy and Asthma Rsch	Seattle	Washington
United States	Allergy and Asthma Diagnostic Treatment Center	Tallahassee	Florida
United States	Toledo Institute of Clinical Research	Toledo	Ohio
United States	Vital Prospects Clinical Research Institute	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Czechia,  Denmark,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Puerto Rico,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first composite event (i.e., relapse (UAS7=16)	The efficacy of remibrutinib in CSU participants with a UAS7<16 at Week 52 in the prior core study with respect to time to first of the three events: relapse or study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication up to Week 24 compared to placebo. (Epoch 1); Time to first composite event (i.e., relapse (UAS7=16), study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication) during the randomized withdrawal period (Epoch 1); Urticaria Activity Score (UAS7) describes the number of hives with 0 being No Hives and 3 is most severe. The final score is calculated by adding together daily scores which can range from 0-6 for 7 days. The resulting maximum score is then 42.	24 weeks
Secondary	Number of participants with treatment-emergent (serious and non-serious) adverse events	Occurrence of treatment-emergent (serious and non-serious) adverse events	160 weeks