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

NCT05107115 | Completed Phase 2 FDA Drug

• 3 other identifiers: DRI17224U1111-1263-42262021-002609-93
• Study Type: interventional
• Target: 161
• Locations: 13 countries
• Sites: 128

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.

Conditions

Chronic Spontaneous Urticaria

Outcome Measures

Primary Outcomes (2)

• Change from baseline in weekly urticaria activity score (UAS7) at Week 12 (except US and US reference countries)

  From baseline to Week 12

• 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 Outcomes (8)

• Change from baseline in UAS7 at Week 4

  From baseline to Week 4

• Change from baseline in ISS7 at Week 12 (except US and US reference countries)

  From baseline to Week 12

• For US and US reference countries only: change from baseline in UAS7 at Week 12

  From baseline to Week 12

• Change from baseline in weekly hives severity score (HSS7) at Week 12

  From baseline to Week 12

• Proportion of participants with UAS7 ≤6 at Week 12

  At Week 12

Study Arms (4)

Rilzabrutinib dose A

EXPERIMENTAL

dose A

Drug: rilzabrutinib

Rilzabrutinib dose B

EXPERIMENTAL

dose B

Drug: rilzabrutinib

Rilzabrutinib dose C

EXPERIMENTAL

dose C

Drug: rilzabrutinib

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: placebo

Interventions

rilzabrutinib DRUG

Tablet, oral use

Also known as: PRN1008/SAR444671

Rilzabrutinib dose A; Rilzabrutinib dose B; Rilzabrutinib dose C

placebo DRUG

Tablet, oral use

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (128)

Investigational Site Number : 0320006

CABA, Buenos Aires, C1055AAO, Argentina

Location

Investigational Site Number :0320006

CABA, Buenos Aires, C1055AAO, Argentina

Location

Investigational Site Number : 0320002

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number :0320002

CABA, Buenos Aires, C1414AIF, Argentina

Location

Investigational Site Number : 0320004

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320005

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number :0320004

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number :0320005

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320003

Rosario, Santa Fe Province, S2000JKR, Argentina

Location

Investigational Site Number :0320003

Rosario, Santa Fe Province, S2000JKR, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number :0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number :1240010

Calgary, Alberta, T2W 4X9, Canada

Location

Investigational Site Number : 1240009

Red Deer, Alberta, T4P 1K4, Canada

Location

Investigational Site Number :1240009

Red Deer, Alberta, T4P 1K4, Canada

Location

Investigational Site Number : 1240005

Toronto, Ontario, M3B 3S6, Canada

Location

Investigational Site Number :1240005

Toronto, Ontario, M3B 3S6, Canada

Location

Investigational Site Number : 1240004

Toronto, Ontario, M5G 1E2, Canada

Location

Investigational Site Number :1240004

Toronto, Ontario, M5G 1E2, Canada

Location

Investigational Site Number : 1240006

Montreal, Quebec, H4A 3T2, Canada

Location

Investigational Site Number :1240006

Montreal, Quebec, H4A 3T2, Canada

Location

Investigational Site Number : 1240002

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Investigational Site Number :1240002

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Investigational Site Number : 1240003

Québec, G1V 4W2, Canada

Location

Investigational Site Number :1240003

Québec, G1V 4W2, Canada

Location

Investigational Site Number : 1520004

Osorno, Los Lagos Region, 5310644, Chile

Location

Investigational Site Number :1520004

Osorno, Los Lagos Region, 5310644, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7640881, Chile

Location

Investigational Site Number :1520001

Santiago, Reg Metropolitana de Santiago, 7640881, Chile

Location

Investigational Site Number :1520003

Santiago, Reg Metropolitana de Santiago, 7750000, Chile

Location

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number :1520002

Santiago, Reg Metropolitana de Santiago, Chile

Location

Investigational Site Number :2760002

Berlin, 10117, Germany

Location

Investigational Site Number : 2760002

Berlin, 12200, Germany

Location

Investigational Site Number : 2760001

Dresden, 01307, Germany

Location

Investigational Site Number :2760001

Dresden, 01307, Germany

Location

Investigational Site Number : 2760005

Kiel, 24105, Germany

Location

Investigational Site Number :2760005

Kiel, 24105, Germany

Location

Investigational Site Number : 2760004

Mainz, 55131, Germany

Location

Investigational Site Number :2760004

Mainz, 55131, Germany

Location

Investigational Site Number : 3000001

Athens, 12462, Greece

Location

Investigational Site Number :3000001

Athens, 12462, Greece

Location

Investigational Site Number : 3000002

Athens, 16121, Greece

Location

Investigational Site Number :3000002

Athens, 16121, Greece

Location

Investigational Site Number : 3000004

N. Efkarpia, 56429, Greece

Location

Investigational Site Number :3000004

N. Efkarpia, 56429, Greece

Location

Investigational Site Number : 3000003

Thessaloniki, 56403, Greece

Location

Investigational Site Number :3000003

Thessaloniki, 56429, Greece

Location

Investigational Site Number : 3800001

Milan, Lombardy, 20122, Italy

Location

Investigational Site Number :3800001

Milan, Lombardy, 20122, Italy

Location

Investigational Site Number :3800004

Milan, Lombardy, 20161, Italy

Location

Investigational Site Number : 3800002

Ancona, 60126, Italy

Location

Investigational Site Number :3800002

Ancona, 60126, Italy

Location

Investigational Site Number : 3800005

Catania, Italy

Location

Investigational Site Number :3800005

Catania, Italy

Location

Investigational Site Number :3920004

Nagoya, Aichi-ken, 454-8509, Japan

Location

Investigational Site Number : 3920005

Chikushino-shi, Fukuoka, 818-0083, Japan

Location

Investigational Site Number :3920005

Chikushino-shi, Fukuoka, 818-0083, Japan

Location

Investigational Site Number : 3920002

Sapporo, Hokkaido, 063-0005, Japan

Location

Investigational Site Number :3920002

Sapporo, Hokkaido, 063-0005, Japan

Location

Investigational Site Number : 3920001

Sagamihara-shi, Kanagawa, 252-0392, Japan

Location

Investigational Site Number :3920001

Sagamihara-shi, Kanagawa, 252-0392, Japan

Location

Investigational Site Number : 3920007

Yokohama, Kanagawa, 221-0825, Japan

Location

Investigational Site Number :3920007

Yokohama, Kanagawa, 221-0825, Japan

Location

Investigational Site Number : 3920006

Izumo-shi, Shimane, 693-8501, Japan

Location

Investigational Site Number :3920006

Izumo-shi, Shimane, 693-8501, Japan

Location

Investigational Site Number : 3920003

Tachikawa-shi, Tokyo, 190-0014, Japan

Location

Investigational Site Number :3920003

Tachikawa-shi, Tokyo, 190-0014, Japan

Location

Investigational Site Number : 3920004

Nagoya, 454-8509, Japan

Location

Investigational Site Number : 5280002

Rotterdam, 3015 GD, Netherlands

Location

Investigational Site Number :5280002

Rotterdam, 3015 GD, Netherlands

Location

Investigational Site Number : 5280001

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number :5280001

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number :6160007

Wroclaw, Lower Silesian Voivodeship, 50-088, Poland

Location

Investigational Site Number : 6160007

Wroclaw, Lower Silesian Voivodeship, 53-673, Poland

Location

Investigational Site Number : 6160001

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Investigational Site Number :6160001

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Investigational Site Number : 6160009

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

Investigational Site Number :6160009

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

Investigational Site Number : 6160008

Krakow, 30-438, Poland

Location

Investigational Site Number :6160008

Krakow, 30-438, Poland

Location

Investigational Site Number : 6160004

Krakow, 31-011, Poland

Location

Investigational Site Number :6160004

Krakow, 31-011, Poland

Location

Investigational Site Number :6160003

Krakow, 31-302, Poland

Location

Investigational Site Number : 6160005

Lodz, 91-211, Poland

Location

Investigational Site Number :6160005

Lodz, 91-211, Poland

Location

Investigational Site Number : 6160006

Wroclaw, 50-566, Poland

Location

Investigational Site Number :6160006

Wroclaw, 50-566, Poland

Location

Investigational Site Number : 6430005

Moscow, 115522, Russia

Location

Investigational Site Number :6430005

Moscow, 115522, Russia

Location

Investigational Site Number :6430006

Moscow, 115522, Russia

Location

Investigational Site Number : 6430002

Moscow, 123182, Russia

Location

Investigational Site Number :6430002

Moscow, 123182, Russia

Location

Investigational Site Number :6430003

Saint Petersburg, 193231, Russia

Location

Investigational Site Number :6430004

Smolensk, 214006, Russia

Location

Investigational Site Number : 6430001

Stavropol, 355020, Russia

Location

Investigational Site Number :6430001

Stavropol, 355020, Russia

Location

Investigational Site Number : 4100002

Busan, Busan, 49241, South Korea

Location

Investigational Site Number :4100002

Busan, Busan, 602-739, South Korea

Location

Investigational Site Number : 4100005

Ansan-si, Gyeonggi-do, 15355, South Korea

Location

Investigational Site Number :4100005

Ansan-si, Gyeonggi-do, 15355, South Korea

Location

Investigational Site Number :4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 06973, South Korea

Location

Investigational Site Number :4100003

Seoul, Seoul-teukbyeolsi, 06973, South Korea

Location

Investigational Site Number : 4100004

Yeongdeunpo-gu, Seoul-teukbyeolsi, Hyllm University Med, South Korea

Location

Investigational Site Number :4100004

Yeongdeunpo-gu, Seoul-teukbyeolsi, Hyllm University Med, South Korea

Location

Investigational Site Number : 7240004

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number :7240004

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Investigational Site Number :7240001

Barcelona, Barcelona [Barcelona], 08003, Spain

Location

Investigational Site Number : 7240008

Barcelona / Sabadell, Catalunya [Cataluña], 08208, Spain

Location

Investigational Site Number :7240008

Barcelona / Sabadell, Catalunya [Cataluña], 08208, Spain

Location

Investigational Site Number :7240007

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Investigational Site Number : 7240006

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number :7240003

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number :7240006

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240005

Alicante, 03010, Spain

Location

Investigational Site Number :7240005

Alicante, 03010, Spain

Location

Investigational Site Number : 7240002

Córdoba, 14004, Spain

Location

Investigational Site Number :7240002

Córdoba, 14004, Spain

Location

Investigational Site Number : 1580002

Hsinchu, 30059, Taiwan

Location

Investigational Site Number :1580002

Hsinchu, 30059, Taiwan

Location

Investigational Site Number : 1580004

Kaohsiung City, 833, Taiwan

Location

Investigational Site Number :1580004

Kaohsiung City, 833, Taiwan

Location

Investigational Site Number : 1580003

Taichung, 40201, Taiwan

Location

Investigational Site Number :1580003

Taichung, 402, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 10002, Taiwan

Location

Investigational Site Number :1580001

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Gimenez-Arnau A, Ferrucci S, Ben-Shoshan M, Mikol V, Lucats L, Sun I, Mannent L, Gereige J. Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria: The RILECSU Phase 2 Randomized Clinical Trial. JAMA Dermatol. 2025 Jul 1;161(7):679-687. doi: 10.1001/jamadermatol.2025.0733.

  PMID: 40266575 DERIVED

MeSH Terms

Conditions

Chronic Urticaria

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 4, 2021
• Study Start: November 24, 2021
• Primary Completion: July 19, 2023
• Study Completion: April 23, 2024
• Last Updated: July 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

RU (9); JP (14); DE (8); AR (12); CL (7); GR (8); IT (7); NL (4); PL (15); TW (8); ES (14); CA (13); KR (9)