Resumen

Este fue un estudio aleatorizado, doble ciego de rilzabrutinib en pacientes con PTI persistente o crónica, con un recuento plaquetario promedio de \<30 000/μL (y ningún recuento plaquetario individual \>35 000/μL) en dos determinaciones con al menos 5 días de diferencia en los 14 días previos al inicio del tratamiento. Los pacientes recibieron rilzabrutinib o placebo 400 mg dos veces al día. Para cada paciente, el estudio tuvo una duración de hasta 60 semanas desde el inicio del período de selección hasta la visita de fin de estudio (FDE). Esto incluyó la selección (hasta 4 semanas), seguida de un período de tratamiento ciego de 12 a 24 semanas y un período abierto de 28 semanas, con un seguimiento posterior a la dosis de 4 semanas. Para los participantes adultos, la duración máxima del período de extensión a largo plazo (ETL) fue de 12 meses desde la fecha en que el último participante adulto ingresó a la ETL. Para los participantes pediátricos, la duración máxima del período de ETL fue de 12 meses desde la fecha en que el último participante pediátrico ingresó a la ETL.

Elegibilidad

Edad mínima: 10 YearsSexo: ALL

Criterios de inclusión

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
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
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.
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 \[Cockcroft and Gault method for adult and Bedside Schwartz Equation for Pediatric participants\])
Hemoglobin \>9 g/dL within 1 week prior to Study Day 1
All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
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

Criterios de exclusión

Patients with secondary ITP
Pregnant or lactating women
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
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
Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)
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
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
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
History of solid organ transplant
Myelodysplastic syndrome
Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study
Planned surgery in the time frame of the dosing period

Ubicaciones

Investigational Site Number : 3206

Capital Federal, Buenos Aires, Argentina

Investigational Site Number : 3211

La Plata, Buenos Aires, Argentina

Investigational Site Number : 3205

Córdoba, Córdoba Province, Argentina

Investigational Site Number : 3209

Corrientes, Argentina

Investigational Site Number : 3208

San Juan, Argentina

Estudio de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos con extensión abierta para evaluar la eficacia y seguridad de rilzabrutinib oral (PRN1008) en adultos y adolescentes con trombocitopenia inmune persistente o crónica (PTI)