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rilzabrutinib

Phase 3

Immunoglobulin G4 Related Disease | Small molecule | Immunology |Sanofi|Last Updated: Jul 13, 2026

Success Probability
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Market & Valuation
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment151
FDA Designations
ORPHAN_DRUGFAST_TRACK
Clinical trial landscape

rilzabrutinib · 14 trials · 10 indications

Phase 3 6Phase 2 6Phase 1 2
NCT07007962Study to Evaluate the Efficacy and Safety of Oral Rilzabrutinib in Adults With Immune Thrombocytopenia (ITP) Who Failed First-line TreatmentImmune Thrombocytopenia
RECRUITING60 Analytics
NCT07216079Rilzabrutinib for the Adult Participants With Chronic ITP Who Have Completed Phase 3 Study in JapanImmune Thrombocytopenia
ACTIVE NOT_RECRUITING4 Analytics
NCT07190196A 52-week Study of Rilzabrutinib Efficacy and Safety Compared to Placebo in Adults Diagnosed With IgG4-related DiseaseImmunoglobulin G4 Related Disease
RECRUITING124 Analytics
NCT07086976A Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Oral Rilzabrutinib Compared With Placebo in Participants 18 Years of Age and Older With Warm Autoimmune Hemolytic AnemiaAutoimmune Haemolytic Anaemia
RECRUITING90 Analytics
NCT06975865The Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell DiseaseSickle Cell Disease
RECRUITING192 Analytics
NCT04562766Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)Immune Thrombocytopenia
ACTIVE NOT_RECRUITING232 Analytics
PHASE3RECRUITING
Study to Evaluate the Efficacy and Safety of Oral Rilzabrutinib in Adults With Immune Thrombocytopenia (ITP) Who Failed First-line Treatment
Immune ThrombocytopeniaUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Rilzabrutinib for the Adult Participants With Chronic ITP Who Have Completed Phase 3 Study in Japan
Immune ThrombocytopeniaUnlock trial analytics
PHASE3RECRUITING
A 52-week Study of Rilzabrutinib Efficacy and Safety Compared to Placebo in Adults Diagnosed With IgG4-related Disease
Immunoglobulin G4 Related DiseaseUnlock trial analytics
PHASE3RECRUITING
A Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Oral Rilzabrutinib Compared With Placebo in Participants 18 Years of Age and Older With Warm Autoimmune Hemolytic Anemia
Autoimmune Haemolytic AnaemiaUnlock trial analytics
PHASE3RECRUITING
The Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease
Sickle Cell DiseaseUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
Immune ThrombocytopeniaUnlock trial analytics
Study Endpoints
Primary Endpoints
Durable platelet response
Until Week 28

Defined as the percentage of participants able to achieve platelet counts ≥50 000/μL (or ≥30 000/μL and \<50 000/μL and at least double from baseline) for ≥50% of 6 biweekly scheduled platelet measurements and at least 4 non-missing, biweekly visits during the last 12 weeks of the primary analysis period (PAP) in absence of rescue therapy

AEs including SAEs and AESIs
Until study completion, approximately 60 weeks

An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor is required

Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period
Until Week 52

The Adjudication Committee will include internationally recognized independent experts in diagnosis and management of patients with IgG4-RD, blinded to participant, investigator, and site identifiers

Proportion of participants achieving DHR. DHR is defined as an increase of Hb by ≥2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the PAP
By Week 24

DHR is defined as an increase of Hb by ≥2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the PAP in the absence of rescue medication and transfusion.

Annualized rate of clinical VOC
At Week 52

Calculated from total number of clinical VOC incidents and total number of days during the observation period

DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in Regions Except European Union and United Kingdom
Up to 24 weeks

Durable platelet response per guidance in regions except European Union and United Kingdom was defined as platelet counts at or above 50,000/mcL for \>=two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, provided that at least 2 non-missing weekly scheduled platelet measurements were at or above 50,000/mcL during the last 6 weeks of the 24-week blinded treatment period.

DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in European Union and United Kingdom
Up to 24 weeks

Durable platelet response per guidance in European Union and United Kingdom was defined as platelet counts at or above 50,000/mcL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy.

Proportion of participants with an LOAC event during the treatment period
Until Week 12

Loss of Asthma Control (LOAC) event is defined as any of the following: * A 30% or greater reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days * ≥6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days * Increase in ICS ≥4 times the last prescribed ICS dose (or ≥50% of the prescribed ICS dose at V2 if background therapy withdrawal completed) * Requiring use of systemic (oral and/or parenteral) steroid treatment * Requiring hospitalization or emergency room visit for asthma exacerbation

Part A: Proportion of participants with overall hemoglobin response
By Week 24 in Part A

Response is defined as an increase in hemoglobin (Hb) by ≥2 g/dL from baseline and an absence of transfusion in the last 7 days, without biochemical resolution of hemolysis at the time response is achieved and an absence of rescue medications during the last 4 weeks. Complete Response is defined as hemoglobin ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, lactate dehydrogenase (LDH) , haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and an absence of rescue medications during the last 4 weeks.

Part B: Proportion of participants who maintain durable response achieved during Part A or achieve a durable response during Part B and have a hemoglobin response
By Week 50 in Part B

Durable response (Part B) is defined as Hb level ≥10 g/dL with an increase from baseline (Part A) of ≥2 g/dL on three consecutive scheduled visits during Week 24 to Week 50; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit.

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
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
Baseline (Day 1) to Week 16

The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in atopic dermatitis (AD). Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of body surface area (BSA) involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Baseline was defined as the Day 1 assessment value.

Proportion of participants who are without disease flare following the first dose of rilzabrutinib until the end of treatment
Up to 64 weeks

Disease flare is defined as an increase in IgG4-RD responder index (RI) \>2 or initiation of rescue treatment.

Incidence of SAE, AE leading to discontinuation and possible glucocorticoid-related AE
Up to 68 weeks
Number of participants with Potentially clinically significant abnormalities (PCSAs) for clinical laboratory tests, vital signs and ECG
Up to 68 weeks
Part A: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts by Starting Dose Level and Overall
Up to 24 Weeks

The percentage of participants who achieved 2 or more consecutive platelet counts, separated by at least 5 days, of \>=50,000/ microliter (μL) and an increase of platelet count of \>=20,000/μL from baseline, by starting dose level and overall, without use of rescue medication in the 4 weeks prior to the latest elevated platelet count. 95% confidence interval (CI) was based on the Clopper-Pearson method. The average of the 2 screening results and the Cycle 1 Day 1 result were used as the baseline value.

Part B: Percentage of Participants Who Achieved Platelet Counts >=50,000/μL
Up to 24 Weeks

The percentage of participants who achieved platelet counts \>=50,000/μL on at least 8 out of the last 12 weeks of the 24-week treatment period without the use of rescue medication after 10 weeks of active treatment. 95% CI was based on the Clopper-Pearson exact method.

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Treatment-Emergent Adverse Events
From first dose of rilzabrutinib (Day 1) up to last dose + 1 (up to 294 days)

Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious on or after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to the rilzabrutinib.

Part B: Number of Participants With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events
From first dose of rilzabrutinib (Day 1) up to last dose + 1 (approximately 170 days)

AE any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious during the treatment-emergent period, defined as any time after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to rilzabrutinib.

Maximum measured concentration of total rilzabrutinib in plasma (Cmax)
Up to 48 hours after the last rilzabrutinib dose
Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)
Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to the last measurable concentration (AUC0-last)
Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Up to 48 hours after the last rilzabrutinib dose
Area under the plasma concentration-time curve of total rilzabrutinib from zero during the dosage interval (AUC0-tau)
Up to 48 hours after the last rilzabrutinib dose
Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)
Up to 48 hours after the last rilzabrutinib dose
Apparent Total Clearance of rilzabrutinib in the plasma after oral administration (CL/F)
Up to 48 hours after the last rilzabrutinib dose
Apparent volume of distribution after oral administration (Vd/F)
Up to 48 hours after the last rilzabrutinib dose
Dose proportionality of rilzabrutinib
Up to 48 hours after the last rilzabrutinib dose
Accumulation ratio (Rac)
Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to t (AUC0-t)
Up to 30 hours after rilzabrutinib dosing
Percent of AUC0-inf extrapolated total rilzabrutinib in plasma (%AUCextrap )
Up to 30 hours after rilzabrutinib dosing
Elimination Rate Constant of total rilzabrutinib (Kel)
Up to 30 hours after rilzabrutinib dosing
Apparent Total Clearance of rilzabrutinib in the plasma after extra-vascular administration (CL/F)
Up to 30 hours after rilzabrutinib dosing
Apparent Volume of Distribution during the Terminal elimination phase after extravascular administration (Vz/F)
Up to 30 hours after rilzabrutinib dosing
Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)
Up to 24 hours after rilzabrutinib dosing
Number of Adverse Events (AE) / Serious Adverse Events (SAE)
From date of signed ICF, up to 9 days after rilzabrutinib dosing
Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities
Up to 30 hours after rilzabrutinib dosing
Secondary Endpoints
Overall platelet response
Until Week 28
Duration of platelet response
Until Week 28
Change from baseline in the immune thrombocytopenia bleeding scale (IBLS) score at the end of week 28
Until Week 28
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
rilzabrutinibEXPERIMENTAL400 mg BID
PlaceboPLACEBO_COMPARATORPlacebo
Rilzabrutinib dose AEXPERIMENTALdose A
Rilzabrutinib dose BEXPERIMENTALdose B
Rilzabrutinib dose CEXPERIMENTALdose C
BID cohort: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).
BID cohort: RilzabrutinibEXPERIMENTALParticipants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).
TID cohort: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
TID cohort: RilzabrutinibEXPERIMENTALParticipants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
Rilzabrutinib + glucocorticoidsEXPERIMENTALRilzabrutinib tablets, 400 mg twice daily from Week 0 to Week 12 plus glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 2 weeks on study)
GlucocorticoidsACTIVE_COMPARATORGlucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 12 weeks on study)
Rilzabrutinib (PRN1008) DailyEXPERIMENTALPart A approximately 60 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension. Part B approximately 25 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension
Cohort 1: RilzabrutinibEXPERIMENTAL -
Cohort 2: RilzabrutinibEXPERIMENTAL -
Rilzabrutinib: Mild Hepatic ImpairmentEXPERIMENTALSubjects with mild Hepatic Impairment (HI)
Rilzabrutinib: Moderate Hepatic ImpairmentEXPERIMENTALSubjects with moderate Hepatic Impairment (HI)
Rilzabrutinib: Healthy-Matched ControlEXPERIMENTALSubjects with normal hepatic function
Interventions
NameTypeDescription
rilzabrutinibDRUGPharmaceutical form:Tablet-Route of administration:Oral
PlaceboDRUGPharmaceutical form:Tablet-Route of administration:Oral
GlucocorticoidDRUGPharmaceutical form:Tablet, solution, suspension formulations according to local standard practices-Route of administration:Oral
GlucocorticoidsDRUGoral tablet or capsule
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites36

Key Inclusion Criteria: * Male or female participants aged 18 years and older with a documented diagnosis of primary ITP in the medical history * Participant received at least one course of first-line therapy and had a history of response while on treatment * Participant has loss of response, relap...

Countries:United StatesAustriaCzechiaFranceGermanyHungaryItalyPolandSpainJapanArgentinaBelgiumCanadaChileChinaIsraelNetherlandsSaudi ArabiaSouth KoreaSwedenTaiwanUnited KingdomBrazilDenmarkGreeceOmanTurkey (Türkiye)AustraliaMexicoNorwayRussiaSingaporeThailandUkraineBulgariaRomania
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Recent Changes (Last 90 Days)
LOWJul 2, 2026NCT07190196lastUpdatePostDate: changed
LOWJul 2, 2026NCT07190196lastUpdatePostDate: changed
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LOWJul 2, 2026NCT07190196lastUpdatePostDate: changed
LOWJun 23, 2026NCT06975865lastUpdatePostDate: changed
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LOWJun 22, 2026NCT07007962lastUpdatePostDate: changed
LOWJun 22, 2026NCT07007962lastUpdatePostDate: changed
LOWJun 5, 2026NCT05002777lastUpdatePostDate: changed
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LOWJun 4, 2026NCT07086976lastUpdatePostDate: changed
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LOWJun 4, 2026NCT07086976lastUpdatePostDate: changed
LOWJun 4, 2026NCT07086976lastUpdatePostDate: changed
LOWJun 2, 2026NCT07190196lastUpdatePostDate: changed
LOWJun 2, 2026NCT07190196lastUpdatePostDate: changed