Clinical trial NCT05107115: Rilzabrutinib for the Treatment of Chronic Spontaneous Urticaria in Patients Who Remain Symptomatic Despite the Use of H1 Antihistamine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-11-04
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in weekly urticaria activity score (UAS7) at Week 12 (except US and US reference countries)
timeFrame: From baseline to Week 12
measure: For US and US reference countries only: change from baseline in weekly itch severity score (ISS7) at Week 12
timeFrame: From baseline to Week 12
Secondary outcomes:
measure: Change from baseline in UAS7 at Week 4
timeFrame: From baseline to Week 4
measure: Change from baseline in ISS7 at Week 12 (except US and US reference countries)
timeFrame: From baseline to Week 12
measure: For US and US reference countries only: change from baseline in UAS7 at Week 12
timeFrame: From baseline to Week 12
measure: Change from baseline in weekly hives severity score (HSS7) at Week 12
timeFrame: From baseline to Week 12
measure: Proportion of participants with UAS7 ≤6 at Week 12
timeFrame: At Week 12
measure: Proportion of participants with UAS7 = 0 at Week 12
timeFrame: At Week 12
measure: 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
timeFrame: Until Week 52
measure: Plasma PK concentrations of rilzabrutinib in participants with CSU
timeFrame: Until Week 52
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Investigational Site Number : 0320006
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320006
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320002
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320004
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number :0320004
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number :0320005
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320003
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number :0320003
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320001
city: Calgary
country: Canada
facility: Investigational Site Number :1240010
state: Alberta
city: Red Deer
country: Canada
facility: Investigational Site Number : 1240009
state: Alberta
city: Red Deer
country: Canada
facility: Investigational Site Number :1240009
state: Alberta
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240005
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240004
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240006
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number :1240006
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number :1240002
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240003
city: Quebec
country: Canada
facility: Investigational Site Number :1240003
city: Osorno
country: Chile
facility: Investigational Site Number : 1520004
state: Los Lagos
city: Osorno
country: Chile
facility: Investigational Site Number :1520004
state: Los Lagos
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520002
state: Reg Metropolitana De Santiago
city: Berlin
country: Germany
facility: Investigational Site Number :2760002
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Dresden
country: Germany
facility: Investigational Site Number : 2760001
city: Dresden
country: Germany
facility: Investigational Site Number :2760001
city: Kiel
country: Germany
facility: Investigational Site Number : 2760005
city: Kiel
country: Germany
facility: Investigational Site Number :2760005
city: Mainz
country: Germany
facility: Investigational Site Number : 2760004
city: Mainz
country: Germany
facility: Investigational Site Number :2760004
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Athens
country: Greece
facility: Investigational Site Number :3000001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Athens
country: Greece
facility: Investigational Site Number :3000002
city: N. Efkarpia
country: Greece
facility: Investigational Site Number : 3000004
city: N. Efkarpia
country: Greece
facility: Investigational Site Number :3000004
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000003
city: Thessaloniki
country: Greece
facility: Investigational Site Number :3000003
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Milano
country: Italy
facility: Investigational Site Number :3800001
state: Lombardia
city: Milano
country: Italy
facility: Investigational Site Number :3800004
state: Lombardia
city: Ancona
country: Italy
facility: Investigational Site Number : 3800002
city: Ancona
country: Italy
facility: Investigational Site Number :3800002
city: Catania
country: Italy
facility: Investigational Site Number : 3800005
city: Catania
country: Italy
facility: Investigational Site Number :3800005
city: Nagoya-shi
country: Japan
facility: Investigational Site Number :3920004
state: Aichi
city: Chikushino-shi
country: Japan
facility: Investigational Site Number : 3920005
state: Fukuoka
city: Chikushino-shi
country: Japan
facility: Investigational Site Number :3920005
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Investigational Site Number :3920002
state: Hokkaido
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Kanagawa
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number :3920001
state: Kanagawa
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number : 3920007
state: Kanagawa
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number :3920007
state: Kanagawa
city: Izumo-shi
country: Japan
facility: Investigational Site Number : 3920006
state: Shimane
city: Izumo-shi
country: Japan
facility: Investigational Site Number :3920006
state: Shimane
city: Tachikawa-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Investigational Site Number :3920003
state: Tokyo
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920004
city: Busan
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Busan-gwangyeoksi
city: Busan
country: Korea, Republic of
facility: Investigational Site Number :4100002
state: Busan-gwangyeoksi
city: Ansan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100005
state: Gyeonggi-do
city: Ansan-si
country: Korea, Republic of
facility: Investigational Site Number :4100005
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100003
state: Seoul-teukbyeolsi
city: Yeongdeunpo-gu
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Yeongdeunpo-gu
country: Korea, Republic of
facility: Investigational Site Number :4100004
state: Seoul-teukbyeolsi
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Rotterdam
country: Netherlands
facility: Investigational Site Number :5280002
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280001
city: Utrecht
country: Netherlands
facility: Investigational Site Number :5280001
city: Wroclaw
country: Poland
facility: Investigational Site Number :6160007
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160007
state: Dolnoslaskie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160001
state: Pomorskie
city: Gdansk
country: Poland
facility: Investigational Site Number :6160001
state: Pomorskie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160009
state: Pomorskie
city: Gdansk
country: Poland
facility: Investigational Site Number :6160009
state: Pomorskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160008
city: Krakow
country: Poland
facility: Investigational Site Number :6160008
city: Krakow
country: Poland
facility: Investigational Site Number : 6160004
city: Krakow
country: Poland
facility: Investigational Site Number :6160004
city: Krakow
country: Poland
facility: Investigational Site Number :6160003
city: Lodz
country: Poland
facility: Investigational Site Number : 6160005
city: Lodz
country: Poland
facility: Investigational Site Number :6160005
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160006
city: Wroclaw
country: Poland
facility: Investigational Site Number :6160006
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430006
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430002
city: Smolensk
country: Russian Federation
facility: Investigational Site Number :6430004
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430003
city: Stavropol
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Stavropol
country: Russian Federation
facility: Investigational Site Number :6430001
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240004
state: Andalucia
city: Sevilla
country: Spain
facility: Investigational Site Number :7240004
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number :7240001
state: Barcelona [Barcelona]
city: Barcelona / Sabadell
country: Spain
facility: Investigational Site Number : 7240008
state: Catalunya [Cataluña]
city: Barcelona / Sabadell
country: Spain
facility: Investigational Site Number :7240008
state: Catalunya [Cataluña]
city: Pozuelo de Alarcón
country: Spain
facility: Investigational Site Number :7240007
state: Madrid
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240006
state: Navarra
city: Pamplona
country: Spain
facility: Investigational Site Number :7240003
state: Navarra
city: Pamplona
country: Spain
facility: Investigational Site Number :7240006
state: Navarra
city: Alicante
country: Spain
facility: Investigational Site Number : 7240005
city: Alicante
country: Spain
facility: Investigational Site Number :7240005
city: Córdoba
country: Spain
facility: Investigational Site Number : 7240002
city: Córdoba
country: Spain
facility: Investigational Site Number :7240002
city: HsinChu
country: Taiwan
facility: Investigational Site Number : 1580002
city: HsinChu
country: Taiwan
facility: Investigational Site Number :1580002
city: Kaohsiung 833
country: Taiwan
facility: Investigational Site Number : 1580004
city: Kaohsiung 833
country: Taiwan
facility: Investigational Site Number :1580004
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taichung
country: Taiwan
facility: Investigational Site Number :1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: