RITUXIMAB for Immune thrombocytopenia (ITP)

Inclusion criteria

• {"criterion_text":"- Male or female aged ≥18 years\n- Diagnosis of primary ITP of less than one-year duration and having a platelet count of < 30 x109/L measured within two weeks prior to inclusion with failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects\n- Failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects.\n- Clinical need for subsequent platelet elevating therapy assessed by the physician in charge\n- Signed and dated written informed consent."}

Exclusion criteria

• {"criterion_text":"- Previous treatment for ITP with: Rituximab, other immune suppressants (including mycophenolate mofetil, azathioprine, cyclosporine), dapsone, danazol, chemotherapy (apart from vincristine as rescue therapy) or splenectomy. Short treatment with any thrombopoietic agent is allowed if given for a limited duration of a maximum of 2 weeks as rescue therapy for quick elevation of platelet count in emergency situations e.g. bleeding\n- Known allergy, sensitivity or contraindication to Rituximab or Avatrombopag\n- Patients in a severely immune compromised state\n- Any contraindication according to the SmPC of Rituximab (e.g. active serious infections (e.g. tuberculosis, opportunistic infections, sepsis) and serious heart failure (NYHAC IV) or serious uncontrolled heart disease) or of Avatrombopag (e.g. cirrhosis and/or severe hepatic impairment).”\n- Presence of active malignancy unless deemed cured by adequate treatment. Participants with the following neoplastic conditions can be included: a.\tMonoclonal gammopathy of undetermined significance (MGUS) or monoclonal B lymphocytosis of undetermined significance (MBUS). b.\tBasal/squamous cell carcinoma of the skin c.\tCarcinoma in situ of the cervix d.\tCarcinoma in situ of the breast e.\tIncidental histological finding of prostate cancer (TNM stage T1a or T1b).\n- Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or any disease that might interfere with the ability to comply with the study protocol or give informed consent\n- Pregnancy or lactation.\n- Females of child-bearing potential refusing to follow effective contraceptive methods (as described in SmPC) for at least 12 months following the last administration of Rituximab or during treatment with Avatrombopag\n- Secondary ITP: ITP secondary to lymphoma or chronic lymphocytic leukemia; ITP secondary to the following autoimmune disorders: Systemic Lupus Erythematosus, or Antiphospholipid Syndrome; ITP secondary to Common Variable Immune Deficiency; ITP secondary the following viral infections: Human Immunodeficiency Virus or Hepatitis C Virus\n- Concomitant autoimmune hemolytic anemia\n- Active hepatitis B virus (positive HBsAg). Patients with HBsAg negative and HBV core antigen antibody positive (HBcAb) should accept to receive entecavir (Baraclude) for 12 months if they will be allocated to Rituximab. Monthly HBV DNA monitoring will be required while on treatment and for the 6 months after the last dose of the study drug\n- Presence of any serious comorbidity where the condition may worsen by and of the study drugs"}

Primary endpoints

• {"endpoint_text":"- Occurrence of durable platelet response defined as achieving platelet counts > 50 X109/L in > 3 of the bi-weekly measurements between weeks 20 and 28 including the last count without having received any other platelet elevating agents after randomization apart from rescue therapy received before end of week 10.","definition_or_measurement_approach":"Durable platelet response measured by platelet counts >50 x10^9/L in more than 3 of the bi-weekly measurements between weeks 20 and 28 (including the last count); requirement of no other platelet elevating agents after randomization except rescue therapy before end of week 10."}

Secondary endpoints

• {"endpoint_text":"- Change in ITP-PAQ (Overall Quality of Life scale) score from baseline to weeks 28 and 78.","definition_or_measurement_approach":"Change from baseline in ITP-PAQ overall QoL at weeks 28 and 78."}
• {"endpoint_text":"- Change in the FACIT-Fatigue score from baseline to weeks 28 and 78.","definition_or_measurement_approach":"Change from baseline in FACIT-Fatigue at weeks 28 and 78."}
• {"endpoint_text":"- Occurrence of SROT defined as: 1.\ta platelet count > 50 X109/L in at least 3 of the 4 planned visits between weeks 36 and 78 including week 78 and; 2.\tno administration of platelet elevating agent between weeks 36 and 78.","definition_or_measurement_approach":"SROT: platelet count >50 x10^9/L in at least 3 of 4 planned visits between weeks 36 and 78 (including week 78) AND no platelet elevating agent between weeks 36 and 78."}
• {"endpoint_text":"- Occurrence of treatment failure anytime during the 3 phases defined as: 1.\tswitching to another platelet elevating agent after randomization to avatrombopag/ rituximab and; 2.\tthrombocytopenia (platelet count <30 X109/L), high risk of bleeding or intolerance of study drug.","definition_or_measurement_approach":"Treatment failure defined by switch to another platelet elevating agent after randomization and/or thrombocytopenia (<30 x10^9/L), high bleeding risk, or intolerance."}
• {"endpoint_text":"- Incremental treatment cost per incremental quality adjusted life-years (QALY) at end of study: Difference in average treatment cost per patient (use of pre-selected resource units collected for each patient, scaled with pertinent unit cost) per arm over entire study period. Difference in average QALYs per patient (SF-36 scores at baseline, weeks 28 and 78 transformed to utility weights multiplied with time under study: area under the curve method). Incremental cost-effectiveness ratio (ICER):","definition_or_measurement_approach":"Health economic analysis using differences in average treatment cost per patient and QALYs derived from SF-36 transformed utilities (AUC method); calculation of ICER."}
• {"endpoint_text":"- Change in summary scores of SF-36 (v2) questionnaires from baseline to weeks 28 and 78 in all randomized patient.","definition_or_measurement_approach":"Change from baseline in SF-36 summary scores at weeks 28 and 78."}
• {"endpoint_text":"- Change in the score of the Treatment Satisfaction Questionnaire for Medication from baseline to weeks 28 and to 78 weeks.","definition_or_measurement_approach":"Change from baseline in Treatment Satisfaction Questionnaire for Medication at weeks 28 and 78."}
• {"endpoint_text":"- Cumulative number of weeks with platelet count > 50 X109/L between randomization and week 78 (including SROT in the Avatrombopag arm) or retreatment. A period of 2 weeks will be deducted after IVIG and 4 weeks after Dexamethasone or Prednisolone including the treatment period.","definition_or_measurement_approach":"Cumulative weeks with platelet count >50 x10^9/L between randomization and week 78, with specified deductions after certain therapies."}
• {"endpoint_text":"- Occurrence of overall response in>3 of the bi-weekly measur between weeks 20 and 28 without the use of rescue therapy after week 10 where overall response is defined as a platelet count >30 X109/L and at least doubling of the lowest platelet count measured during the prescreening period of 2 weeks, in > 80% of the measurements between weeks 20 and 28 without the use of rescue therapy or corticosteroids after week 10","definition_or_measurement_approach":"Overall response: platelet count >30 x10^9/L and at least doubling of nadir prescreening platelet, in >80% of measurements between weeks 20-28, without rescue therapy or corticosteroids after week 10."}
• {"endpoint_text":"- Cumulative dose of dexamethasone /prednisolone, cumulative dose of IVIG, number of platelet transfusions, from time of randomization to treatment failure or week 28.","definition_or_measurement_approach":"Cumulative exposure measures (steroid dose, IVIG dose, number of platelet transfusions) from randomization to treatment failure or week 28."}
• {"endpoint_text":"- Number and severity of WHO bleeding events. Change in Khellaf score from baseline to weeks 28 and 78.","definition_or_measurement_approach":"Number/severity of WHO bleeding events and change in Khellaf score at weeks 28 and 78."}
• {"endpoint_text":"- Occurrence and severity of treatment emergent adverse events Occurrence and severity of adverse events of special interest including infections leading to hospitalization or death, arterial and venous thrombosis and bone marrow fibrosis (bone marrow biopsy showing MF2 or higher).","definition_or_measurement_approach":"Safety endpoints: TEAEs and AESIs including serious infections, thromboses, and bone marrow fibrosis (MF2+)."}

Norway

Earliest CTIS Part Ii Submission Date

20-12-2023

Latest Decision Or Authorization Date

30-01-2024

Processing Time Days

41

Number Of Sites

12

Number Of Participants

220

Primary sponsor

Full Name

Ostfold Hospital Trust

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway