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

Immune Thrombocytopenia Clinical Trial

— LUNA 3  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04562766
• Other study ID #: EFC17093
• Secondary ID: PRN1008-0182023-
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2020
• Est. completion date: November 20, 2026

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind study of rilzabrutinib in participants 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. Participants will receive rilzabrutinib or placebo 400mg twice daily.

For each participant, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 194
• Est. completion date: November 20, 2026
• Est. primary completion date: June 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

1. Participants 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. Participants 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 contraindication 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 participants 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 × 10^9/L, AST/ALT =1.5 × upper limit of normal [ULN], albumin =3 g/dL, total bilirubin =1.5 × ULN [unless the partcipant has documented Gilbert syndrome], glomerular filtration rate >50 [Cockcroft and Gault method])

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. Participants must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the participants' guardian and agree to the schedule of assessments.

Exclusion Criteria:

1. Participants 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

• Participants 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); participant should not be using an investigational device at the time of dosing

• Participants 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

• Participants 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

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Rilzabrutinib
400mg Caplet
• Placebo
400mg Caplet

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 3206	Capital Federal	Buenos Aires
Argentina	Investigational Site Number : 3205	Cordoba	Córdoba
Argentina	Investigational Site Number : 3209	Corrientes
Argentina	Investigational Site Number : 3211	La Plata	Buenos Aires
Argentina	Investigational Site Number : 3208	San Juan
Australia	Investigational Site Number : 3609	Adelaide	South Australia
Australia	Investigational Site Number : 3611	Brisbane	Queensland
Australia	Investigational Site Number : 3606	Frankston	Victoria
Australia	Investigational Site Number : 3607	Kogarah	New South Wales
Australia	Investigational Site Number : 3610	Perth	Western Australia
Australia	Investigational Site Number : 3608	Westmead	New South Wales
Austria	Investigational Site Number : 4005	Graz
Austria	Investigational Site Number : 4004	Leoben
Austria	Investigational Site Number : 4001	Linz
Austria	Investigational Site Number : 4003	Steyr
Austria	Investigational Site Number : 4002	Wien
Brazil	CEMEC Oncologica do Brasil Site Number : 7606	Belem Do Para
Brazil	Uniao Oeste Paranaense de Estudos e Combates ao Cancer Site Number : 7610	Cascavel	Paraná
Brazil	Hospital De Clinicas De Porto Alegre Site Number : 7605	Porto Alegre	Rio Grande Do Sul
Brazil	HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti Site Number : 7609	Rio de Janeiro
Brazil	Hospital Sao Rafael Instituto D'Or da Bahia Site Number : 7608	Salvador	Bahia
Brazil	Hospital Santa Marcelina Site Number : 7611	Sao Paulo	São Paulo
Brazil	Hospital do Servidor Publico Estadual de Sao Paulo Site Number : 7607	São Paulo
Canada	Investigational Site Number : 12404	Edmonton	Alberta
Canada	CHU Sainte-Justine_Investigational site number 12405	Montréal	Quebec
Canada	Investigational Site Number : 12406	Toronto	Ontario
Chile	Investigational Site Number : 15201	La Serena	Coquimbo
Chile	Investigational Site Number : 15204	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 15202	Vina del Mar	Valparaíso
China	Investigational Site Number : 15611	Hangzhou
China	Investigational Site Number : 15608	Hefei
China	Qilu Hospital of Shandong University - Investigational Site Number: 15605	Jinan	Shandong
China	Second Affiliated Hospital of Kunming Medical University - Investigational Site Number: 15604	Kunming	Yunnan
China	Investigational Site Number : 15610	Nanchang
China	Shengjing Hospital of China Medical University - Investigational Site Number: 15603	Shenyang	Liaoning
China	Investigational Site Number : 15613	Tangshan
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences - Investigational Site Number: 15602	Tianjin	Tianjin
China	Wuhan Union Hospital of Tongji Medical College of HUST - Investigational Site Number: 15601	Wuhan	Hubei
China	Investigational Site Number : 15609	Wuxi
China	Shaanxi Provincial People's Hospital - Investigational Site Number: 15607	Xi'an	Shaanxi
China	Investigational Site Number : 15614	ZhenJiang
France	Investigational Site Number : 25014	Angers
France	Investigational Site Number : 25011	Creteil
France	Investigational Site Number : 25010	Dijon cedex
France	Investigational Site Number : 25009	Nantes Cedex 1
France	Investigational Site Number : 25008	Paris
France	Investigational Site Number : 25012	Paris
France	Investigational Site Number : 25007	Pessac
Germany	Investigational Site Number : 27610	Berlin
Germany	Investigational Site Number 27612	Düsseldorf
Germany	Investigational Site Number : 27613	Frankfurt am Main
Germany	Investigational Site Number : 27611	Recklinghausen
Hungary	Investigational Site Number : 34803	Budapest
Hungary	Investigational Site Number : 34805	Debrecen
Hungary	Investigational Site Number : 34801	Gyor
Hungary	Investigational Site Number : 34804	Nyíregyháza
Hungary	Investigational Site Number : 34802	Szekesfehervar
Israel	Investigational Site Number : 37605	Haifa
Israel	Investigational Site Number : 37606	Kfar Saba
Israel	Investigational Site Number : 37607	Tel Aviv
Israel	Investigational Site Number : 37608	Tel Hashomer
Israel	Investigational Site Number : 37609	Zerifin
Italy	Investigational Site Number : 38012	Bologna
Italy	Investigational Site Number : 38014	Firenze	Toscana
Italy	Investigational Site Number : 38013	Milano
Italy	Investigational Site Number : 38015	Milano
Italy	Investigational Site Number : 38010	Trieste
Italy	Investigational Site Number : 38011	Vicenza
Japan	Investigational Site Number : 39208	Bunkyo-ku	Tokyo
Japan	Investigational Site Number : 39212	Chiba
Japan	Investigational Site Number : 39203	Hiroshima City
Japan	Investigational Site Number : 39201	Iruma-gun	Saitama
Japan	Investigational Site Number : 39205	Kanazawa-shi	Ishikawa
Japan	Investigational Site Number : 39210	Meguro-ku	Tokyo
Japan	Investigational Site Number : 39207	Sagamihara-shi	Kanagawa
Japan	Investigational Site Number : 39206	Saitama-shi
Japan	Investigational Site Number : 39204	Setagaya	Tokyo
Japan	Investigational Site Number : 39202	Suita-shi	Osaka
Japan	Investigational Site Number : 39209	Sumida-ku	Tokyo
Japan	Investigational Site Number : 39214	Tsuchiura-shi	Ibaraki
Korea, Republic of	Investigational Site Number : 41004	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number : 41003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 41005	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 41006	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 41001	Suwon	Gyeonggi-do
Mexico	Investigational Site Number : 48402	Chihuahua
Mexico	Investigational Site Number : 48406	Ciudad de México
Mexico	Investigational Site Number : 48405	Delegacion Benito Juarez
Mexico	Investigational Site Number : 48404	Durango
Mexico	Investigational Site Number : 48401	Monterrey	Nuevo León
Mexico	Investigational Site Number : 48403	Zapopan
Netherlands	Erasmus MC_Investigational Site Number 52801	Rotterdam
Norway	Investigational Site Number : 57802	Bergen
Norway	Investigational Site Number : 57801	Gralum
Poland	Investigational Site Number : 61615	Gdynia
Poland	Investigational Site Number : 61617	Pila	Wielkopolskie
Poland	Investigational Site Number : 61614	Poznan
Poland	Investigational Site Number : 61609	Slupsk	Pomorskie
Poland	Investigational Site Number : 61612	Warszawa
Poland	Investigational Site Number : 61613	Wroclaw
Russian Federation	Investigational Site Number : 64305	Moscow
Russian Federation	Investigational Site Number : 64307	Moscow
Russian Federation	Investigational Site Number : 64304	Novosibirsk
Russian Federation	Investigational Site Number : 64301	Pyatigorsk
Russian Federation	Investigational Site Number : 64306	Samara
Russian Federation	Investigational Site Number : 64302	St. Petersburg
Russian Federation	Investigational Site Number : 64303	Tula
Singapore	Investigational Site Number : 70201	Singapore
Singapore	Investigational Site Number : 70202	Singapore
Singapore	Investigational Site Number : 70203	Singapore
Spain	Investigational Site Number : 72409	Barcelona
Spain	Investigational Site Number : 72412	Barcelona
Spain	Investigational Site Number : 72414	Barcelona
Spain	Investigational Site Number : 72416	Burgos
Spain	Investigational Site Number : 72410	Madrid
Spain	Investigational Site Number : 72408	Malaga	Málaga
Spain	Investigational Site Number : 72411	Murcia
Spain	Investigational Site Number : 72413	Sevilla
Spain	Investigational Site Number : 72407	Valencia / Valencia	Valenciana, Comunidad
Thailand	Investigational Site Number : 76404	Bangkok
Thailand	Investigational Site Number : 76405	Bangkok
Thailand	Investigational Site Number : 76402	Chiangmai
Thailand	Investigational Site Number : 76401	Khon Kaen
Thailand	Investigational Site Number : 76403	Songkla
Turkey	Investigational Site Number 79208	Ankara
Turkey	Investigational Site Number 79210	Istanbul
Turkey	Investigational Site Number 79206	Izmir
Turkey	Investigational Site Number 79209	Kayseri
Ukraine	Investigational Site Number : 80408	Dnipropetrovsk
Ukraine	Investigational Site Number : 80409	Kryvyi Rih City
Ukraine	Investigational Site Number : 80410	Kyiv
United Kingdom	Investigational Site Number : 82604	Harrow
United Kingdom	Investigational Site Number : 82606	London
United Kingdom	Investigational Site Number : 82607	London	London, City Of
United Kingdom	Investigational Site Number : 82609	London
United Kingdom	Investigational Site Number : 82603	Manchester
United Kingdom	Investigational Site Number : 82605	Norfolk
United Kingdom	Investigational Site Number : 82608	Southampton
United States	Children's Healthcare of Atlanta_Investigational Site Number 84034	Atlanta	Georgia
United States	Children's Hospital Colorado_Investigational Site Number 84025	Aurora	Colorado
United States	Massachusetts General Hospital Site Number : 84038	Boston	Massachusetts
United States	Montefiore Medical Center_Investigational Site Number 84032	Bronx	New York
United States	IMMUNOe International Research Centers_Investigational Site Number 84028	Centennial	Colorado
United States	Rush University Medical Center_Investigational Site Number 84029	Chicago	Illinois
United States	Cleveland Clinic_Investigational Site Number 84026	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center Site Number : 84036	Cleveland	Ohio
United States	University of Southern California_Investigational Site Number 84024	Los Angeles	California
United States	University of Louisville - James Graham Brown Cancer Center_Investigational Site Number 84033	Louisville	Kentucky
United States	The Children's Hospital of Philadelphia (CHOP)_Investigational Site Number 84027	Philadelphia	Pennsylvania
United States	University of Utah-Huntsman Cancer Institute_Investigational Site Number 84035	Salt Lake City	Utah
United States	UCSF Benioff Children's Hospital San Francisco_Investigational Site Number 84020	San Francisco	California
United States	University of Washington Medical Centre Site Number : 84041	Seattle	Washington
United States	Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center_Investigational Site Number 84037	Torrance	California
United States	ASCLEPES Research Centers_Investigational Site Number 84023	Weeki Wachee	Florida
United States	The Oncology Institute of Hope and Innovation_Investigational Site Number 84031	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Principia Biopharma, a Sanofi Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Russian Federation,  Singapore,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Durable platelet response during the last 6 weeks of the 24-week blinded treatment period (not for EU and UK)	Durable platelet response is defined as a proportion of participants able to achieve platelet counts at or above 50,000/µL 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 are at or above 50,000/µL.	24 weeks
Primary	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		24 weeks
Secondary	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		24 weeks
Secondary	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		24 weeks
Secondary	Time to first platelet count of =50,000/µL OR between =30,000/µL and <50,000/µL and doubled from baseline		24 weeks
Secondary	Proportion of participants requiring rescue therapy during the 24-week blinded treatment period		24 weeks
Secondary	Change from baseline on Item 10 of the ITP-Patient Assessment Questionnaire in adult participants (=18 years) at Week 13		From baseline to Week 13
Secondary	for EU and UK: Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25		At Week 25
Secondary	Proportion of participants able to achieve stable platelet response, within a period of 24 weeks following initial achievement of the platelet response	Stable platelet response is defined as no 2 scheduled visits, at least 4 weeks apart, with a platelet count less than 50,000/µL, without an intervening visit with a platelet count =50,000/µL. Initial platelet response defined as platelet count =50,000/µL within 12 weeks of initiation of treatment with rilzabrutinib during the study.	24 weeks
Secondary	Frequency and severity of Treatment Emergent Adverse Events	Including physical examination, ECG, clinical laboratory test results, vital signs and laboratory tests (serum chemistry, hematology, except for platelet counts included in the primary efficacy endpoint)	52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
Secondary	Frequency and severity of bleeding TEAEs		52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
Secondary	Plasma concentrations of rilzabrutinib		Until 52 weeks
Secondary	Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult participants (=18 years)	The ITP Patient Assessment Questionnaire™ (ITP-PAQ™) is a disease-specific instrument that was designed to measure the Quality of Life (QoL) of adult participants with immune thrombocytopenia. The items employ a 4-week recall with responses recorded on 4-, 5- or 7-point Likert scales. All item scores are transformed to a 0 to 100 continuum where higher scores represent better QoL and are weighted equally to derive the scale scores.	52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose
Secondary	Change from baseline in disease-specific QoL as measured by the Kids' ITP Tools (ITP-KIT) score in pediatric participants	The ITP-KIT include a battery of three disease-specific instruments, a child self-report form designed to be completed by children =7 years, a parent proxy report form for children <7 and a parent impact form. Respondents record their disease experience based on a 1-week recall. The instrument yields a total score which is the summation of the items converted to a 0 to 100 score with higher scores indicating better disease-specific QoL.	52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose