Open-label, Randomized Controlled Trial to Assess Efficacy and Safety of Rituximab in Patients With Acute Rheumatic Fever in Africa

AGRAF-2

Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.

2023-01-05

2024-09-30

2025-02-01

Early phase I

234

Inclusion Criteria: * Children aged between \>= 5 and \< 17 years old; * Diagnosed acute rheumatic fever with at least one progressive rheumatic valvular lesion confirmed through a cardiac echography. * Informed consent, signed and dated by both parents or legal guardians of the patient Exclusion Criteria: * Simultaneous active infection, such as HIV, hepatitis B, C, tuberculosis, Epstein-Barr virus (EBV), or history of frequent, unusual or serious infections ; * Pathologies likely to affect immunity (cancer, multiple sclerosis, diabetes, other auto-immune diseases) * Recent history of drug administration that may affect the immune system, for the past 4 weeks (immunosuppressive drugs, corticosteroids, anticancer drugs); * Hypersensitivity reaction to rituximab or one of its components. Hypersensitivity to penicillin * History of monoclonal antibodies administration * Recent vaccination (less than a month) or planned within the 12 months after randomization; * History of heart failure * Renal failure with a creatinine clearance \<45 ml/min/1,73m² * Pregnancy (a negative urinary test is necessary for women who had their first menstruations or aged 14 years old and more) * Patients diagnosed with Guillain-Barré syndrome * Patient with at least one of the following biological features : Hemoglobin \< 8,5 g/dL, Platelets \< 100 G/L, Neutrophils \< 1,5 G/L, Leucocytes \< 3 G/L, AST or ALT increased \> 2,5 the normal superior limit) * Any acute or chronic infection clinically significant which would limitate the patient's capacity to follow up the study protocol, which remains under appreciation of the investigator. * Any participation in another clinical trial in the 6 months before the pre-randomization visit

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2024-06-11