Rilzabrutinib for the Treatment of Chronic Spontaneous Urticaria in Patients Who Remain Symptomatic Despite the Use of H1 Antihistamine

Chronic Spontaneous Urticaria Clinical Trial

— RILECSU  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-ranging Phase 2 Study of Rilzabrutinib Followed by an Open-label Extension Phase in Patients With Moderate-to-severe Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite the Use of H1 Antihistamine Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05107115
• Other study ID #: DRI17224
• Secondary ID: U1111-1263-4226D
• Status: Completed
• Phase: Phase 2
• Start date: November 24, 2021
• Est. completion date: April 23, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The first phase of this study will be a parallel, 12-week treatment, Phase 2, double-blind, 4 arm study to assess the safety and effectiveness of 3 oral doses of SAR444671 (rilzabrutinib), i.e. dose A, B and C, compared with placebo for decreasing the frequency and severity of itch and urticaria in male and female participants aged 18 years inclusive or older with CSU. After completion of the double-blind phase of the study, participants will be given the option of enrolling in the 40-week open label extension (OLE) phase of the study. Participants will receive open-label rilzabrutinib at dose C (the dose may be modified based on the 12-week safety and efficacy data). Due to the fact that some participants may be receiving rilzabrutinib for the first time, all participants will be monitored at Week 14, Week 16, Week 20, and Week 24. Afterwards, participants will be monitored at Week 36 and Week 52.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: April 23, 2024
• Est. primary completion date: July 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Participants who have a diagnosis of CSU refractory to H1-AH at the time of randomization
• Diagnosis of CSU =3 months prior to screening visit (Visit 1).
• The presence of itch and hives for =6 consecutive weeks at any time prior to screening visit (Visit 1) despite the use of H1-AH during this time period.
• Participants using a study defined H1-AH for CSU treatment. For participants on stable doses of non-study-approved H1-AH, investigators may switch participants to an equivalent dose of a study-approved H1-AH maintenance medication.
• Participants who are omalizumab naïve OR omalizumab-incomplete responders.
• Participants must be willing and able to complete a daily symptom e-diary for the duration of the study.
• During the 7 days before randomization: UAS7 =16 and ISS7 =8.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

• Clearly defined underlying etiology for CUs other than CSU (main manifestation being physical urticaria).
• Presence of skin morbidities other than CSU that may interfere with the assessment of the study outcomes.
• Participants with active atopic dermatitis (AD).
• Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study.
• Known or suspected immunodeficiency, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the Investigator.
• History of serious infections requiring intravenous (IV) therapy with the potential for recurrence (as judged by the Site Investigator) with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher), including active coronavirus disease 2019 (COVID-19).
• Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
• Active malignancy or history of malignancy within 5 years.
• Conditions that may predispose the participant to excessive bleeding
• Any participant with an uncontrolled disease state as judged by the Investigator, such as asthma, psoriasis, or inflammatory bowel disease, etc. that are typically treated with oral or parenteral corticosteroids
• Previous use of a BTK inhibitor.
• Has received any investigational drug (or is currently using an investigational device) within the 30 days before Day 1, or at least 5 times the respective elimination half-life time (whichever is longer).
• Previous exposure to another investigative drug for CSU.
• Positive for human immunodeficiency virus (HIV) antibody test.
• Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with positive DNA test result at screening or within 3 months prior to the screening visit.
• Positive hepatitis C antibody test result at screening or within 3 months prior to the screening visit.
• Tuberculosis infection.
• Any of significant laboratory abnormalities and ECG findings at the screening visit. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• rilzabrutinib
Tablet, oral use
• placebo
Tablet, oral use

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Argentina	Investigational Site Number :0320001	Buenos Aires
Argentina	Investigational Site Number : 0320002	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320006	Caba	Buenos Aires
Argentina	Investigational Site Number :0320002	Caba	Buenos Aires
Argentina	Investigational Site Number :0320006	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320003	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320004	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Argentina	Investigational Site Number :0320003	Rosario	Santa Fe
Argentina	Investigational Site Number :0320004	Rosario	Santa Fe
Argentina	Investigational Site Number :0320005	Rosario	Santa Fe
Canada	Investigational Site Number :1240010	Calgary	Alberta
Canada	Investigational Site Number : 1240006	Montreal	Quebec
Canada	Investigational Site Number :1240006	Montreal	Quebec
Canada	Investigational Site Number : 1240003	Quebec
Canada	Investigational Site Number :1240003	Quebec
Canada	Investigational Site Number : 1240009	Red Deer	Alberta
Canada	Investigational Site Number :1240009	Red Deer	Alberta
Canada	Investigational Site Number : 1240004	Toronto	Ontario
Canada	Investigational Site Number : 1240005	Toronto	Ontario
Canada	Investigational Site Number :1240004	Toronto	Ontario
Canada	Investigational Site Number :1240005	Toronto	Ontario
Canada	Investigational Site Number : 1240002	Trois-Rivieres	Quebec
Canada	Investigational Site Number :1240002	Trois-Rivieres	Quebec
Chile	Investigational Site Number : 1520004	Osorno	Los Lagos
Chile	Investigational Site Number :1520004	Osorno	Los Lagos
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago
Germany	Investigational Site Number : 2760002	Berlin
Germany	Investigational Site Number :2760002	Berlin
Germany	Investigational Site Number : 2760001	Dresden
Germany	Investigational Site Number :2760001	Dresden
Germany	Investigational Site Number : 2760005	Kiel
Germany	Investigational Site Number :2760005	Kiel
Germany	Investigational Site Number : 2760004	Mainz
Germany	Investigational Site Number :2760004	Mainz
Greece	Investigational Site Number : 3000001	Athens
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number :3000001	Athens
Greece	Investigational Site Number :3000002	Athens
Greece	Investigational Site Number : 3000004	N. Efkarpia
Greece	Investigational Site Number :3000004	N. Efkarpia
Greece	Investigational Site Number : 3000003	Thessaloniki
Greece	Investigational Site Number :3000003	Thessaloniki
Italy	Investigational Site Number : 3800002	Ancona
Italy	Investigational Site Number :3800002	Ancona
Italy	Investigational Site Number : 3800005	Catania
Italy	Investigational Site Number :3800005	Catania
Italy	Investigational Site Number : 3800001	Milano	Lombardia
Italy	Investigational Site Number :3800001	Milano	Lombardia
Italy	Investigational Site Number :3800004	Milano	Lombardia
Japan	Investigational Site Number : 3920005	Chikushino-shi	Fukuoka
Japan	Investigational Site Number :3920005	Chikushino-shi	Fukuoka
Japan	Investigational Site Number : 3920006	Izumo-shi	Shimane
Japan	Investigational Site Number :3920006	Izumo-shi	Shimane
Japan	Investigational Site Number : 3920004	Nagoya-shi
Japan	Investigational Site Number :3920004	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920001	Sagamihara-shi	Kanagawa
Japan	Investigational Site Number :3920001	Sagamihara-shi	Kanagawa
Japan	Investigational Site Number : 3920002	Sapporo-shi	Hokkaido
Japan	Investigational Site Number :3920002	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920003	Tachikawa-shi	Tokyo
Japan	Investigational Site Number :3920003	Tachikawa-shi	Tokyo
Japan	Investigational Site Number : 3920007	Yokohama-Shi	Kanagawa
Japan	Investigational Site Number :3920007	Yokohama-Shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100005	Ansan-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100005	Ansan-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100002	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number :4100002	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100004	Yeongdeunpo-gu	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100004	Yeongdeunpo-gu	Seoul-teukbyeolsi
Netherlands	Investigational Site Number : 5280002	Rotterdam
Netherlands	Investigational Site Number :5280002	Rotterdam
Netherlands	Investigational Site Number : 5280001	Utrecht
Netherlands	Investigational Site Number :5280001	Utrecht
Poland	Investigational Site Number : 6160001	Gdansk	Pomorskie
Poland	Investigational Site Number : 6160009	Gdansk	Pomorskie
Poland	Investigational Site Number :6160001	Gdansk	Pomorskie
Poland	Investigational Site Number :6160009	Gdansk	Pomorskie
Poland	Investigational Site Number : 6160004	Krakow
Poland	Investigational Site Number : 6160008	Krakow
Poland	Investigational Site Number :6160003	Krakow
Poland	Investigational Site Number :6160004	Krakow
Poland	Investigational Site Number :6160008	Krakow
Poland	Investigational Site Number : 6160005	Lodz
Poland	Investigational Site Number :6160005	Lodz
Poland	Investigational Site Number : 6160006	Wroclaw
Poland	Investigational Site Number : 6160007	Wroclaw	Dolnoslaskie
Poland	Investigational Site Number :6160006	Wroclaw
Poland	Investigational Site Number :6160007	Wroclaw	Dolnoslaskie
Russian Federation	Investigational Site Number : 6430002	Moscow
Russian Federation	Investigational Site Number : 6430005	Moscow
Russian Federation	Investigational Site Number :6430002	Moscow
Russian Federation	Investigational Site Number :6430005	Moscow
Russian Federation	Investigational Site Number :6430006	Moscow
Russian Federation	Investigational Site Number :6430004	Smolensk
Russian Federation	Investigational Site Number :6430003	St-Petersburg
Russian Federation	Investigational Site Number : 6430001	Stavropol
Russian Federation	Investigational Site Number :6430001	Stavropol
Spain	Investigational Site Number : 7240005	Alicante
Spain	Investigational Site Number :7240005	Alicante
Spain	Investigational Site Number : 7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240008	Barcelona / Sabadell	Catalunya [Cataluña]
Spain	Investigational Site Number :7240008	Barcelona / Sabadell	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240002	Córdoba
Spain	Investigational Site Number :7240002	Córdoba
Spain	Investigational Site Number : 7240006	Pamplona	Navarra
Spain	Investigational Site Number :7240003	Pamplona	Navarra
Spain	Investigational Site Number :7240006	Pamplona	Navarra
Spain	Investigational Site Number :7240007	Pozuelo de Alarcón	Madrid
Spain	Investigational Site Number : 7240004	Sevilla	Andalucia
Spain	Investigational Site Number :7240004	Sevilla	Andalucia
Taiwan	Investigational Site Number : 1580002	HsinChu
Taiwan	Investigational Site Number :1580002	HsinChu
Taiwan	Investigational Site Number : 1580004	Kaohsiung 833
Taiwan	Investigational Site Number :1580004	Kaohsiung 833
Taiwan	Investigational Site Number : 1580003	Taichung
Taiwan	Investigational Site Number :1580003	Taichung
Taiwan	Investigational Site Number : 1580001	Taipei
Taiwan	Investigational Site Number :1580001	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Argentina,  Canada,  Chile,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in weekly urticaria activity score (UAS7) at Week 12 (except US and US reference countries)		From baseline to Week 12
Primary	For US and US reference countries only: change from baseline in weekly itch severity score (ISS7) at Week 12		From baseline to Week 12
Secondary	Change from baseline in UAS7 at Week 4		From baseline to Week 4
Secondary	Change from baseline in ISS7 at Week 12 (except US and US reference countries)		From baseline to Week 12
Secondary	For US and US reference countries only: change from baseline in UAS7 at Week 12		From baseline to Week 12
Secondary	Change from baseline in weekly hives severity score (HSS7) at Week 12		From baseline to Week 12
Secondary	Proportion of participants with UAS7 =6 at Week 12		At Week 12
Secondary	Proportion of participants with UAS7 = 0 at Week 12		At Week 12
Secondary	Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and withdrawals due to TEAEs during the double-blind period and the open label extension		Until Week 52
Secondary	Plasma PK concentrations of rilzabrutinib in participants with CSU		Until Week 52