Clinical trial NCT04562766: Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Oral Rilzabrutinib (PRN1008) in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Immune Thrombocytopenia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-09-24
Enrollment: 232
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of \<30,000/μL (and no single platelet count \>35,000/μL) on two counts at least 5 days apart in the 14 days before treatment begins. Patients will receive rilzabrutinib or placebo 400mg twice daily.

For each patient, the study will last up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This includes Screening (up to 4 weeks) through a 12 to 24-week Blinded Treatment Period followed by a 28-week Open-Label Period. Followed by a 4-week post dose follow-up.

For adult participants, the maximum duration of the long-term extension (LTE) period will be 12 months from the date of the last adult participant to enter the LTE.

For pediatric participants, the maximum duration of the LTE period will be 12 months from the date of the last pediatric participant to enter the LTE.


Eligibility criteria: Inclusion Criteria:

1. Patients will be male and female with primary ITP with duration of \>6 months in pediatric participants aged 12 to \<18 years (pediatric participants aged 10 to \<12 years will be enrolled in the EU \[EEA countries\] only) and duration of \>3 months in ages 18 years and above
2. Patients who had a response (achievement of platelet count ≥50,000/µL) to IVIg/anti-D or CSs that was not sustained and who have documented intolerance, insufficient response or any contra-indication to any appropriate courses of standard of care ITP therapy
3. An average of 2 platelet counts at least 5 days apart of \<30,000/µL during the Screening period and no single platelet count \>35,000/µL, within 14 days prior to the first dose of study drug.

   - Pediatric patients must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator.
4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 10\^9/L, AST/ALT ≤1.5 x upper limit of normal \[ULN\], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN \[unless the patient has documented Gilbert syndrome\], glomerular filtration rate \>50 \[Cockcroft and Gault method for adult and Bedside Schwartz Equation for Pediatric participants\])
5. Hemoglobin \>9 g/dL within 1 week prior to Study Day 1
6. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Patients must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the patient's guardian and agree to the schedule of assessments

Exclusion Criteria:

1. Patients with secondary ITP
2. Pregnant or lactating women
3. History (within 5 years of Study Day 1) or current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non melanoma skin cancer
4. Transfusion with blood, blood products, plasmapheresis, or use of any other rescue medications with intent to increase platelet count within 14 days before Study Day 1
5. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)
6. Immunosuppressant drugs other than CSs within 5 times the elimination half-life of the drug or 14 days of Study Day 1, whichever is longer
7. Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1

   - Patients treated with rituximab will have normal B-cell counts prior to enrollment
8. Has received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient should not be using an investigational device at the time of dosing

   * Patients who previously received treatment with Bruton's Tyrosine Kinase (BTK) inhibitors (except rilzabrutinib) within 30 days before the first dose of study drug are not eligible
   * Patients who previously received rilzabrutinib at any time are not eligible
9. History of solid organ transplant
10. Myelodysplastic syndrome
11. Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study
12. Planned surgery in the time frame of the dosing period

Primary outcomes:
measure: Durable platelet response during the last 6 weeks of the 24-week blinded treatment period (not for EU and UK)
timeFrame: 24 weeks
measure: for EU and UK: Proportion of adult participants able to achieve platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy
timeFrame: 24 weeks
Secondary outcomes:
measure: Number of weeks with platelet count ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy
timeFrame: 24 weeks
measure: Number of weeks with platelet counts ≥30,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy
timeFrame: 24 weeks
measure: Time to first platelet count of ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and doubled from baseline
timeFrame: 24 weeks
measure: Proportion of patients requiring rescue therapy during the 24-week blinded treatment period
timeFrame: 24 weeks
measure: Change from baseline on Item 10 of the ITP-Patient Assessment Questionnaire in adult patients (≥18 years) at Week 13
timeFrame: From baseline to Week 13
measure: for EU and UK: Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25
timeFrame: At Week 25
measure: Proportion of participants who able to achieve stable platelet response, within a period of 24 weeks following initial achievement of the platelet response
timeFrame: 24 weeks
measure: Frequency and severity of Treatment Emergent Adverse Events
timeFrame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
measure: Frequency and severity of bleeding TEAEs
timeFrame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
measure: Plasma concentrations of rilzabrutinib
timeFrame: Until 52 weeks
measure: Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult patients (≥18 years)
timeFrame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
measure: Change from baseline in disease-specific QoL as measured by the Kids' ITP Tools (ITP-KIT) score in pediatric participants
timeFrame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California_Investigational Site Number 84024
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital San Francisco_Investigational Site Number 84020
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center_Investigational Site Number 84037
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation_Investigational Site Number 84031
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado_Investigational Site Number 84025
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe International Research Centers_Investigational Site Number 84028
state: Colorado
city: Weeki Wachee
country: United States
facility: ASCLEPES Research Centers_Investigational Site Number 84023
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta_Investigational Site Number 84034
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center_Investigational Site Number 84029
state: Illinois
city: Louisville
country: United States
facility: University of Louisville - James Graham Brown Cancer Center_Investigational Site Number 84033
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital Site Number : 84038
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center_Investigational Site Number 84032
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center Site Number : 84036
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic_Investigational Site Number 84026
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia (CHOP)_Investigational Site Number 84027
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah-Huntsman Cancer Institute_Investigational Site Number 84035
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Centre Site Number : 84041
state: Washington
city: Capital Federal
country: Argentina
facility: Investigational Site Number : 3206
state: Buenos Aires
city: La Plata
country: Argentina
facility: Investigational Site Number : 3211
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Investigational Site Number : 3205
state: Córdoba
city: Corrientes
country: Argentina
facility: Investigational Site Number : 3209
city: San Juan
country: Argentina
facility: Investigational Site Number : 3208
city: Kogarah
country: Australia
facility: Investigational Site Number : 3607
state: New South Wales
city: Westmead
country: Australia
facility: Investigational Site Number : 3608
state: New South Wales
city: Brisbane
country: Australia
facility: Investigational Site Number : 3611
state: Queensland
city: Adelaide
country: Australia
facility: Investigational Site Number : 3609
state: South Australia
city: Frankston
country: Australia
facility: Investigational Site Number : 3606
state: Victoria
city: Perth
country: Australia
facility: Investigational Site Number : 3610
state: Western Australia
city: Graz
country: Austria
facility: Investigational Site Number : 4005
city: Leoben
country: Austria
facility: Investigational Site Number : 4004
city: Linz
country: Austria
facility: Investigational Site Number : 4001
city: Steyr
country: Austria
facility: Investigational Site Number : 4003
city: Wien
country: Austria
facility: Investigational Site Number : 4002
city: Salvador
country: Brazil
facility: Hospital Sao Rafael Instituto D'Or da Bahia Site Number : 7608
state: Bahia
city: Cascavel
country: Brazil
facility: Uniao Oeste Paranaense de Estudos e Combates ao Cancer Site Number : 7610
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital De Clinicas De Porto Alegre Site Number : 7605
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina Site Number : 7611
state: São Paulo
city: Belem Do Para
country: Brazil
facility: CEMEC Oncologica do Brasil Site Number : 7606
city: Rio de Janeiro
country: Brazil
facility: HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti Site Number : 7609
city: São Paulo
country: Brazil
facility: Hospital do Servidor Publico Estadual de Sao Paulo Site Number : 7607
city: Edmonton
country: Canada
facility: Investigational Site Number : 12404
state: Alberta
city: Toronto
country: Canada
facility: Investigational Site Number : 12406
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine_Investigational site number 12405
state: Quebec
city: La Serena
country: Chile
facility: Investigational Site Number : 15201
state: Coquimbo
city: Santiago
country: Chile
facility: Investigational Site Number : 15204
state: Reg Metropolitana De Santiago
city: Vina del Mar
country: Chile
facility: Investigational Site Number : 15202
state: Valparaíso
city: Wuhan
country: China
facility: Wuhan Union Hospital of Tongji Medical College of HUST - Investigational Site Number: 15601
state: Hubei
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University - Investigational Site Number: 15603
state: Liaoning
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital - Investigational Site Number: 15607
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University - Investigational Site Number: 15605
state: Shandong
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences - Investigational Site Number: 15602
state: Tianjin
city: Kunming
country: China
facility: Second Affiliated Hospital of Kunming Medical University - Investigational Site Number: 15604
state: Yunnan
city: Hangzhou
country: China
facility: Investigational Site Number : 15611
city: Hefei
country: China
facility: Investigational Site Number : 15608
city: Nanchang
country: China
facility: Investigational Site Number : 15610
city: Tangshan
country: China
facility: Investigational Site Number : 15613
city: Wuxi
country: China
facility: Investigational Site Number : 15609
city: ZhenJiang
country: China
facility: Investigational Site Number : 15614
city: Angers
country: France
facility: Investigational Site Number : 25014
city: Creteil
country: France
facility: Investigational Site Number : 25011
city: Dijon cedex
country: France
facility: Investigational Site Number : 25010
city: Nantes Cedex 1
country: France
facility: Investigational Site Number : 25009
city: Paris
country: France
facility: Investigational Site Number : 25008
city: Paris
country: France
facility: Investigational Site Number : 25012
city: Pessac
country: France
facility: Investigational Site Number : 25007
city: Berlin
country: Germany
facility: Investigational Site Number : 27610
city: Düsseldorf
country: Germany
facility: Investigational Site Number 27612
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number : 27613
city: Recklinghausen
country: Germany
facility: Investigational Site Number : 27611
city: Budapest
country: Hungary
facility: Investigational Site Number : 34803
city: Debrecen
country: Hungary
facility: Investigational Site Number : 34805
city: Gyor
country: Hungary
facility: Investigational Site Number : 34801
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number : 34804
city: Szekesfehervar
country: Hungary
facility: Investigational Site Number : 34802
city: Haifa
country: Israel
facility: Investigational Site Number : 37605
city: Kfar Saba
country: Israel
facility: Investigational Site Number : 37606
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 37607
city: Tel Hashomer
country: Israel
facility: Investigational Site Number : 37608
city: Zerifin
country: Israel
facility: Investigational Site Number : 37609
city: Firenze
country: Italy
facility: Investigational Site Number : 38014
state: Toscana
city: Bologna
country: Italy
facility: Investigational Site Number : 38012
city: Milano
country: Italy
facility: Investigational Site Number : 38015
city: Milano
country: Italy
facility: Investigational Site Number : 38013
city: Trieste
country: Italy
facility: Investigational Site Number : 38010
city: Vicenza
country: Italy
facility: Investigational Site Number : 38011
city: Tsuchiura-shi
country: Japan
facility: Investigational Site Number : 39214
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Investigational Site Number : 39205
state: Ishikawa
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number : 39207
state: Kanagawa
city: Suita-shi
country: Japan
facility: Investigational Site Number : 39202
state: Osaka
city: Iruma-gun
country: Japan
facility: Investigational Site Number : 39201
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Investigational Site Number : 39208
state: Tokyo
city: Meguro-ku
country: Japan
facility: Investigational Site Number : 39210
state: Tokyo
city: Setagaya
country: Japan
facility: Investigational Site Number : 39204
state: Tokyo
city: Sumida-ku
country: Japan
facility: Investigational Site Number : 39209
state: Tokyo
city: Chiba
country: Japan
facility: Investigational Site Number : 39212
city: Hiroshima City
country: Japan
facility: Investigational Site Number : 39203
city: Saitama-shi
country: Japan
facility: Investigational Site Number : 39206
city: Busan
country: Korea, Republic of
facility: Investigational Site Number : 41004
state: Busan-gwangyeoksi
city: Suwon
country: Korea, Republic of
facility: Investigational Site Number : 41001
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 41003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 41005
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 41006
state: Seoul-teukbyeolsi
city: Monterrey
country: Mexico
facility: Investigational Site Number : 48401
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 48402
city: Ciudad de México
country: Mexico
facility: Investigational Site Number : 48406
city: Delegacion Benito Juarez
country: Mexico
facility: Investigational Site Number : 48405
city: Durango
country: Mexico
facility: Investigational Site Number : 48404
city: Zapopan
country: Mexico
facility: Investigational Site Number : 48403
city: Rotterdam
country: Netherlands
facility: Erasmus MC_Investigational Site Number 52801
city: Bergen
country: Norway
facility: Investigational Site Number : 57802
city: Gralum
country: Norway
facility: Investigational Site Number : 57801
city: Slupsk
country: Poland
facility: Investigational Site Number : 61609
state: Pomorskie
city: Pila
country: Poland
facility: Investigational Site Number : 61617
state: Wielkopolskie
city: Gdynia
country: Poland
facility: Investigational Site Number : 61615
city: Poznan
country: Poland
facility: Investigational Site Number : 61614
city: Warszawa
country: Poland
facility: Investigational Site Number : 61612
city: Wroclaw
country: Poland
facility: Investigational Site Number : 61613
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 64307
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 64305
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number : 64304
city: Pyatigorsk
country: Russian Federation
facility: Investigational Site Number : 64301
city: Samara
country: Russian Federation
facility: Investigational Site Number : 64306
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number : 64302
city: Tula
country: Russian Federation
facility: Investigational Site Number : 64303
city: Singapore
country: Singapore
facility: Investigational Site Number : 70201
city: Singapore
country: Singapore
facility: Investigational Site Number : 70202
city: Singapore
country: Singapore
facility: Investigational Site Number : 70203
city: Malaga
country: Spain
facility: Investigational Site Number : 72408
state: Málaga
city: Valencia / Valencia
country: Spain
facility: Investigational Site Number : 72407
state: Valenciana, Comunidad
city: Barcelona
country: Spain
facility: Investigational Site Number : 72412
city: Barcelona
country: Spain
facility: Investigational Site Number : 72414
city: Barcelona
country: Spain
facility: Investigational Site Number : 72409
city: Burgos
country: Spain
facility: Investigational Site Number : 72416
city: Madrid
country: Spain
facility: Investigational Site Number : 72410
city: Murcia
country: Spain
facility: Investigational Site Number : 72411
city: Sevilla
country: Spain
facility: Investigational Site Number : 72413
city: Bangkok
country: Thailand
facility: Investigational Site Number : 76405
city: Bangkok
country: Thailand
facility: Investigational Site Number : 76404
city: Chiangmai
country: Thailand
facility: Investigational Site Number : 76402
city: Khon Kaen
country: Thailand
facility: Investigational Site Number : 76401
city: Songkla
country: Thailand
facility: Investigational Site Number : 76403
city: Ankara
country: Turkey
facility: Investigational Site Number 79208
city: Istanbul
country: Turkey
facility: Investigational Site Number 79210
city: Izmir
country: Turkey
facility: Investigational Site Number 79206
city: Kayseri
country: Turkey
facility: Investigational Site Number 79209
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number : 80408
city: Kryvyi Rih City
country: Ukraine
facility: Investigational Site Number : 80409
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 80410
city: London
country: United Kingdom
facility: Investigational Site Number : 82607
state: London, City Of
city: Harrow
country: United Kingdom
facility: Investigational Site Number : 82604
city: London
country: United Kingdom
facility: Investigational Site Number : 82606
city: London
country: United Kingdom
facility: Investigational Site Number : 82609
city: Manchester
country: United Kingdom
facility: Investigational Site Number : 82603
city: Norfolk
country: United Kingdom
facility: Investigational Site Number : 82605
city: Southampton
country: United Kingdom
facility: Investigational Site Number : 82608
Study officials:
References: