Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) (LUNA 3)

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)

This was 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 received rilzabrutinib or placebo 400mg twice daily.

For each patient, the study lasted up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This included 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 was 12 months from the date of the last adult participant to enter the LTE.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Rilzabrutinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 232
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Corrientes, Argentina, W3410 FND
    • Investigational Site Number : 3209
  • San Juan, Argentina, 5400
    • Investigational Site Number : 3208
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1280AEB
      • Investigational Site Number : 3206
    • La Plata, Buenos Aires, Argentina, B1900
      • Investigational Site Number : 3211
  • Córdoba Province
    • Córdoba, Córdoba Province, Argentina, X5003DCE
      • Investigational Site Number : 3205
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Investigational Site Number : 3607
    • Westmead, New South Wales, Australia, 2145
      • Investigational Site Number : 3608
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Investigational Site Number : 3611
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Investigational Site Number : 3609
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Investigational Site Number : 3606
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Investigational Site Number : 3610
• Austria
  • Graz, Austria, 8036
    • Investigational Site Number : 4005
  • Leoben, Austria, 8700
    • Investigational Site Number : 4004
  • Linz, Austria, A4020
    • Investigational Site Number : 4001
  • Steyr, Austria, 4400
    • Investigational Site Number : 4003
  • Vienna, Austria, 1140
    • Investigational Site Number : 4002
• Brazil
  • Belém, Brazil, 66053-000
    • CEMEC Oncologica do Brasil Site Number : 7606
  • Rio de Janeiro, Brazil, 20211030
    • HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti Site Number : 7609
  • São Paulo, Brazil, 04039-004
    • Hospital do Servidor Publico Estadual de Sao Paulo Site Number : 7607
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253190
      • Hospital Sao Rafael Instituto D'Or da Bahia Site Number : 7608
  • Paraná
    • Cascavel, Paraná, Brazil, 85806-300
      • Uniao Oeste Paranaense de Estudos e Combates ao Cancer Site Number : 7610
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035 003
      • Hospital De Clinicas De Porto Alegre Site Number : 7605
  • São Paulo
    • São Paulo, São Paulo, Brazil, 08270-070
      • Hospital Santa Marcelina Site Number : 7611
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2P4
      • Investigational Site Number : 12404
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Investigational Site Number : 12406
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine_Investigational site number 12405
• Chile
  • Coquimbo Region
    • La Serena, Coquimbo Region, Chile, 1720430
      • Investigational Site Number : 15201
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500653
      • Investigational Site Number : 15204
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 322000
      • Investigational Site Number : 15202
• China
  • Hangzhou, China, 310018
    • Investigational Site Number : 15611
  • Hefei, China
    • Investigational Site Number : 15608
  • Nanchang, China, 330006
    • Investigational Site Number : 15610
  • Tangshan, China, 63000
    • Investigational Site Number : 15613
  • Wuxi, China, 214023
    • Investigational Site Number : 15609
  • Zhenjiang, China, 212001
    • Investigational Site Number : 15614
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital of Tongji Medical College of HUST - Investigational Site Number: 15601
  • Liaoning
    • Shenyang, Liaoning, China, 110022
      • Shengjing Hospital of China Medical University - Investigational Site Number: 15603
  • Shaanxi
    • Xi'an, Shaanxi, China, 710068
      • Shaanxi Provincial People's Hospital - Investigational Site Number: 15607
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University - Investigational Site Number: 15605
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences - Investigational Site Number: 15602
  • Yunnan
    • Kunming, Yunnan, China, 650101
      • Second Affiliated Hospital of Kunming Medical University - Investigational Site Number: 15604
• France
  • Angers, France, 49933
    • Investigational Site Number : 25014
  • Créteil, France, 94000
    • Investigational Site Number : 25011
  • Dijon, France, 21079
    • Investigational Site Number : 25010
  • Nantes, France, 44093
    • Investigational Site Number : 25009
  • Paris, France, 75012
    • Investigational Site Number : 25008
  • Paris, France, 75019
    • Investigational Site Number : 25012
  • Pessac, France, 33600
    • Investigational Site Number : 25007
• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number : 27610
  • Düsseldorf, Germany, 40497
    • Investigational Site Number 27612
  • Frankfurt am Main, Germany, 60596
    • Investigational Site Number : 27613
  • Recklinghausen, Germany, 45659
    • Investigational Site Number : 27611
• Hungary
  • Budapest, Hungary, 1083
    • Investigational Site Number : 34803
  • Debrecen, Hungary, 4032
    • Investigational Site Number : 34805
  • Győr, Hungary, 9024
    • Investigational Site Number : 34801
  • Nyíregyháza, Hungary, 4405
    • Investigational Site Number : 34804
  • Székesfehérvár, Hungary, 8000
    • Investigational Site Number : 34802
• Israel
  • Haifa, Israel, 3109601
    • Investigational Site Number : 37605
  • Kfar Saba, Israel, 4428164
    • Investigational Site Number : 37606
  • Tel Aviv, Israel, 6423906
    • Investigational Site Number : 37607
  • Tel Litwinsky, Israel, 52621
    • Investigational Site Number : 37608
  • Ẕerifin, Israel, 70300
    • Investigational Site Number : 37609
• Italy
  • Bologna, Italy, 40138
    • Investigational Site Number : 38012
  • Milan, Italy, 20123
    • Investigational Site Number : 38015
  • Milan, Italy, 20142
    • Investigational Site Number : 38013
  • Trieste, Italy, 34125
    • Investigational Site Number : 38010
  • Vicenza, Italy, 36100
    • Investigational Site Number : 38011
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Investigational Site Number : 38014
• Japan
  • Chiba, Japan, 60-0852
    • Investigational Site Number : 39212
  • Hiroshima, Japan, 730-8619
    • Investigational Site Number : 39203
  • Saitama-shi, Japan, 330-8777
    • Investigational Site Number : 39206
  • Ibaraki
    • Tsuchiura-shi, Ibaraki, Japan
      • Investigational Site Number : 39214
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8530
      • Investigational Site Number : 39205
  • Kanagawa
    • Sagamihara-shi, Kanagawa, Japan, 252-0375
      • Investigational Site Number : 39207
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Investigational Site Number : 39202
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Investigational Site Number : 39201
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Investigational Site Number : 39208
    • Meguro-ku, Tokyo, Japan, 152-8902
      • Investigational Site Number : 39210
    • Setagaya City, Tokyo, Japan, 157-0074
      • Investigational Site Number : 39204
    • Sumida-ku, Tokyo, Japan, 130-8575
      • Investigational Site Number : 39209
• Mexico
  • Chihuahua City, Mexico, 31200
    • Investigational Site Number : 48402
  • Delegacion Benito Juarez, Mexico, 03720
    • Investigational Site Number : 48405
  • Durango, Mexico, 34000
    • Investigational Site Number : 48404
  • Mexico City, Mexico, 06760
    • Investigational Site Number : 48406
  • Zapopan, Mexico, 45030
    • Investigational Site Number : 48403
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Investigational Site Number : 48401
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC_Investigational Site Number 52801
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number : 57802
  • Grålum, Norway, 1714
    • Investigational Site Number : 57801
• Poland
  • Gdynia, Poland, 81-519
    • Investigational Site Number : 61615
  • Poznan, Poland, 61 696
    • Investigational Site Number : 61614
  • Warsaw, Poland, 02-776
    • Investigational Site Number : 61612
  • Wroclaw, Poland, 50-556
    • Investigational Site Number : 61613
  • Greater Poland Voivodeship
    • Piła, Greater Poland Voivodeship, Poland, 64-920
      • Investigational Site Number : 61617
  • Pomeranian Voivodeship
    • Słupsk, Pomeranian Voivodeship, Poland, 76-200
      • Investigational Site Number : 61609
• Russia
  • Moscow, Russia, 119049
    • Investigational Site Number : 64307
  • Moscow, Russia, 125167
    • Investigational Site Number : 64305
  • Novosibirsk, Russia, 630090
    • Investigational Site Number : 64304
  • Pyatigorsk, Russia, 357502
    • Investigational Site Number : 64301
  • Saint Petersburg, Russia, 191024
    • Investigational Site Number : 64302
  • Samara, Russia, 443099
    • Investigational Site Number : 64306
  • Tula, Russia, 300053
    • Investigational Site Number : 64303
• Singapore
  • Singapore, Singapore, 119228
    • Investigational Site Number : 70201
  • Singapore, Singapore, 169608
    • Investigational Site Number : 70202
  • Singapore, Singapore, 308433
    • Investigational Site Number : 70203
• South Korea
  • Busan
    • Busan, Busan, South Korea, 49241
      • Investigational Site Number : 41004
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Investigational Site Number : 41001
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 02841
      • Investigational Site Number : 41003
    • Seoul, Seoul-teukbyeolsi, South Korea, 03080
      • Investigational Site Number : 41005
    • Seoul, Seoul-teukbyeolsi, South Korea, 03722
      • Investigational Site Number : 41006
• Spain
  • Barcelona, Spain, 08035
    • Investigational Site Number : 72412
  • Barcelona, Spain, 08035
    • Investigational Site Number : 72414
  • Barcelona, Spain, 08041
    • Investigational Site Number : 72409
  • Burgos, Spain
    • Investigational Site Number : 72416
  • Madrid, Spain, 28007
    • Investigational Site Number : 72410
  • Murcia, Spain, 30008
    • Investigational Site Number : 72411
  • Seville, Spain, 41013
    • Investigational Site Number : 72413
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Investigational Site Number : 72408
  • Valenciana, Comunidad
    • Valencia, Valenciana, Comunidad, Spain, 46010
      • Investigational Site Number : 72407
• Thailand
  • Bangkok, Thailand, 10330
    • Investigational Site Number : 76405
  • Bangkok, Thailand, 10400
    • Investigational Site Number : 76404
  • Chiang Mai, Thailand, 50200
    • Investigational Site Number : 76402
  • Khon Kaen, Thailand, 40002
    • Investigational Site Number : 76401
  • Songkhla, Thailand, 90110
    • Investigational Site Number : 76403
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06620
    • Investigational Site Number 79208
  • Istanbul, Turkey (Türkiye), 34093
    • Investigational Site Number 79210
  • Izmir, Turkey (Türkiye), 35100
    • Investigational Site Number 79206
  • Kayseri, Turkey (Türkiye), 38039
    • Investigational Site Number 79209
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Investigational Site Number : 80408
  • Kryvyi Rih, Ukraine, 50025
    • Investigational Site Number : 80409
  • Kyiv, Ukraine, 03143
    • Investigational Site Number : 80410
• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Investigational Site Number : 82604
  • London, United Kingdom, SE5 9PJ
    • Investigational Site Number : 82606
  • London, United Kingdom, W2 1NY
    • Investigational Site Number : 82609
  • Manchester, United Kingdom, M13 9WL
    • Investigational Site Number : 82603
  • Norfolk, United Kingdom, NR31 6LA
    • Investigational Site Number : 82605
  • Southampton, United Kingdom, SO16 6YD
    • Investigational Site Number : 82608
  • London, City of
    • London, London, City of, United Kingdom, W12 0HS
      • Investigational Site Number : 82607
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California_Investigational Site Number 84024
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital San Francisco_Investigational Site Number 84020
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center_Investigational Site Number 84037
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation_Investigational Site Number 84031
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado_Investigational Site Number 84025
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Centers_Investigational Site Number 84028
  • Florida
    • Weeki Wachee, Florida, United States, 34607
      • ASCLEPES Research Centers_Investigational Site Number 84023
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta_Investigational Site Number 84034
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center_Investigational Site Number 84029
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville - James Graham Brown Cancer Center_Investigational Site Number 84033
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Site Number : 84038
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center_Investigational Site Number 84032
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center Site Number : 84036
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic_Investigational Site Number 84026
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia (CHOP)_Investigational Site Number 84027
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah-Huntsman Cancer Institute_Investigational Site Number 84035
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Centre Site Number : 84041

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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. Had 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rilzabrutinib; Patients receive rilzabrutinib 400mg orally twice daily for up to 24 weeks followed by 28 weeks of open label period	Drug: Rilzabrutinib; 400mg Caplet; Other Names: PRN1008
Placebo Comparator: Placebo; Patients receive matching placebo 400mg orally twice daily for up to 24 weeks	Drug: Placebo; 400mg Caplet; Other Names: PRN1008 Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Number of Weeks With Platelet Count >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy	Number of weeks with platelet response was assessed using clinically meaningful threshold of platelet count >=50,000/mcL or between >=30,000/mcL and <50,000/mcL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy.	Up to 24 weeks
DB Period: Number of Weeks With Platelet Counts >=30,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy	Number of weeks with platelet response was assessed using clinically meaningful threshold of platelet counts >=30,000/mcL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy.	Up to 24 weeks
DB Period: Time to First Platelet Count of >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and Doubled From Baseline	Time to first platelet count of >=50,000/mcL or between >=30,000/mcL and <50,000/mcL and doubled from baseline was calculated as: (date of first occurrence of platelet response - date of first study drug intake) + 1.	Up to 24 weeks
DB Period: Percentage of Participants Who Required Rescue Therapy	Resue therapy included intravenous immunoglobulin (Ig) or high-dose corticosteroids, platelet infusion, or anti-D Ig infusion. Percentage of participants who required rescue therapy are presented.	Up to 24 weeks
DB Period: Change From Baseline on Item 10 (Physical Fatigue) of the Immune Thrombocytopenia-Patient Assessment Questionnaire (ITP-PAQ) in Adult Participants at Week 13	ITP-PAQ:38 items and 44 items completed by male and female respondents respectively.It included 10 scales:symptoms(6 items:1-6),fatigue/sleep(4 items:7-10),bother-physical health(3 items:11-13),activity(2 items:14-15),psychological health(5 items:16-20),fear(5 items:21-25),overall quality of life(QoL)(5 items:26-30),social activity(4 items:31-34),women's reproductive health(6 items:35-40),work(4 items:41-44).Responses were recorded on 4-point(1:"strongly disagree" to 4:"strongly agree"),5-point(1:"never/not at all" to 5:"all the time/extremely") or 7-point(1:"not at all" to 7:"extremely") Likert scales.Each item score:100x([possible maximal item score - item score]/range).All item scores:transformed to 0 to 100 continuum and were weighted equally to derive scale scores.Total score:0(worst) to 100(best);higher scores:better QoL.Change of positive value:improvement.Change from baseline in physical fatigue is presented.Baseline:last available value before first dose of DB study drug.	Baseline (Day 1) and Week 13
DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) Assessment in Adult Participants at Week 25 Per Guidance in European Union and United Kingdom	Per guidance in European Union and United Kingdom, ITP IBLS was a bleeding assessment system which comprised of 11 (10 for male) site-specific grades assessed at 9 anatomical sites by history (Hx) over previous period. In addition, 2 of these sites, skin and oral, were also assessed by physical examination (PE). These 11 grades included: skin (PE), skin (Hx), oral (PE), oral (Hx), epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage; scores ranged from 0 (none) to 2 (marked bleeding). For each participant, an IBLS score at each visit was calculated by taking average across 11 items (10 for male and postmenopausal female) at 9 sites (8 for male and postmenopausal female). Total score was calculated as mean value for all 11 grades ranging from 0 (best) to 22 (worst); higher scores indicated worse outcomes. Change of negative value indicates an improvement.Baseline:last available value before first dose of DB study drug.	Baseline (Day 1) and Week 25
DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale Assessment in Adolescent Participants at Week 25 Per Guidance in European Union and United Kingdom	Per guidance in European Union and United Kingdom, ITP IBLS was a bleeding assessment system which comprised of 11 (10 for male) site-specific grades assessed at 9 anatomical sites by Hx over previous period. In addition, 2 of these sites, skin and oral, were also assessed by PE. These 11 grades included: skin (PE), skin (Hx), oral (PE), oral (Hx), epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage; scores ranged from 0 (none) to 2 (marked bleeding). For each participant, an IBLS score at each visit was calculated by taking average across 11 items (10 for male) at 9 sites (8 for male). Total score was calculated as mean value for all 11 grades ranging from 0 (best) to 22 (worst); higher scores indicated worse outcomes. Change of negative value indicates an improvement. Baseline:last available value before first dose of DB study drug.	Baseline (Day 1) and Week 25
DB-OL Period: Percentage of Participants With Stability of Response in Adult Participants	Stability of response was defined as the percentage of participants who were able to achieve stable platelet response defined as no 2 scheduled visits, at least 4 weeks apart, with a platelet count <50,000/mcL, without an intervening visit with a platelet count >=50,000/mcL, within a period of 24 weeks following initial achievement of the platelet response (initial platelet response defined as platelet count >=50,000/mcL within 12 weeks of initiation of treatment with rilzabrutinib during the study). This endpoint was assessed from start of DB period through OL period.	Up to 52 weeks
DB-OL Period: Percentage of Participants With Stability of Response in Adolescent Participants		Up to 52 weeks
DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Bleeding Treatment-Emergent Adverse Events >=Grade 2	An AE was any untoward medical occurrence in a participant or clinical investigation participant, administered a study drug and which did not necessarily had a causal relationship with the study drug. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period. Bleeding TEAEs Grade >=2 (criteria mentioned in statistical analysis plan) are also presented.	From first dose of study drug (Day 1) up to maximum DB exposure, up to 182 days (adults) and up to 175 days (adolescent)
DB Period: Plasma Concentrations of Rilzabrutinib	Blood samples were collected at specified timepoints for the analysis of plasma concentration of rilzabrutinib.	Pre-dose at Weeks 1, 13 and 25 and 2 hours post-dose at Week 1 and 25 (adults); Pre-dose at Weeks 1, 13 and 25, 0.5, 2, 4 and 6 hours post-dose at Weeks 1 and 25 (adolescent)
DB Period: Change From Baseline in the Symptoms, Bother and Activity Domains of the Immune Thrombocytopenia-Patient Assessment Questionnaire in Adult Participants	ITP-PAQ:38 items and 44 items completed by male and female respondents respectively.It included 10 scales:symptoms(6 items:1-6),fatigue/sleep(4 items:7-10),bother-physical health(3 items:11-13),activity(2 items:14-15),psychological health(5 items:16-20),fear(5 items:21-25),overall QoL(5 items:26-30),social activity(4 items:31-34),women's reproductive health(6 items:35-40),work(4 items:41-44).Responses were recorded on 4-point(1:"strongly disagree" to 4:"strongly agree"),5-point(1:"never/not at all" to 5:"all the time/extremely") or 7-point(1:"not at all" to 7:"extremely") Likert scales.Each item score:100x([possible maximal item score - item score]/range).All item scores:transformed to 0 to 100 continuum and were weighted equally to derive scale scores.Total score:0(worst) to 100(best);higher scores:better QoL.Change of positive value:improvement.Change from baseline in symptoms,bother and activity domains is presented.Baseline:last available value before first dose of DB study drug.	Baseline (Day 1) and Week 25
DB Period: Change From Baseline in Disease-Specific Quality Of Life as Measured by the Kids' Immune Thrombocytopenia Tools (ITP-KIT) Score in Adolescent Participants	ITP-KIT was a disease-specific instrument and child self-report form designed to be completed by children >=7 years. It comprised of total of 27 items among which 26 items were structured as Likert scales with 5 response options 1: "never", 2: "rarely", 3: "sometimes", 4: "often" and 5: "always". An additional "not applicable" option was available for items 18 to 26, which was scored as 1: the same as "never". Item 27 was a descriptive question answered "yes" or "no" which was not included in the calculation of the summary score. Instrument yielded a summary KIT score which was the summation of the items calculated as: 100 x (1- [{sum of all valid responses - number of valid responses}/{number of valid responses*4}]). Scores were converted to a 0 to 100 with higher scores indicating better disease-specific QoL. Change from baseline of positive value indicated improvement. Baseline was defined as the last available value before first dose of DB study drug.	Baseline (Day 1) and Week 25

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company

Publications and helpful links

General Publications

• Lin J, Radhakrishnan J. What Are Baskets, Umbrellas, and Platforms Doing in Nephrology Clinical Trials? J Am Soc Nephrol. 2025 Feb 3;36(8):1652-1654. doi: 10.1681/ASN.0000000648. No abstract available.
• Kuter DJ, Ghanima W, Cooper N, Liebman HA, Zhang L, Hu Y, Miyakawa Y, Homenda W, Galindo LEM, Basquiera AL, Tan CW, Saydam G, Hutter-Kronke ML, Chai-Adisaksopha C, Gomez-Almaguer D, Tran H, Shin HJ, Dantas da Cunha Junior A, Lazar Z, Izquierdo CP, Kirgner I, Lucchini E, Kuzmina G, Fillitz M, Audia S, Taparia M, Cordoba M, Diab R, Yao M, Gouia I, Lee M, Daak A. Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Blood. 2025 Jun 12;145(24):2914-2926. doi: 10.1182/blood.2024027336.
• Kuter DJ, Bussel JB, Ghanima W, Cooper N, Gernsheimer T, Lambert MP, Liebman HA, Tarantino MD, Lee M, Guo H, Daak A. Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study. Ther Adv Hematol. 2023 Oct 18;14:20406207231205431. doi: 10.1177/20406207231205431. eCollection 2023.

Helpful Links

• EFC17093 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): January 15, 2025
• Study Completion (Estimated): August 26, 2026

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: EFC17093; PRN1008-018 (Other Identifier: Sanofi Identifier); 2023-509401-71 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No