4.1. Clinical Cohort
DISEASE, ALKAPTONURIA, RHEUMATIC DISEASES
SONIA 2 (NCT01916382) was a 4-year, open-label, evaluator-blind, multicentre, randomized, no-treatment controlled, parallel-group study to investigate the efficacy and safety of nitisinone in patients with AKU. AKU was diagnosed through a positive urine homogentisic acid (HGA) measurement. During SONIA 2, serum and 24-h urine HGA was measured. Genetic mutations were analysed during the study, but these were not required for diagnosis or entry into SONIA 2. Inclusion and exclusion criteria can be found in [The study was conducted at three sites: Royal Liverpool University Hospital, Liverpool, UK; Hôpital Necker-Enfants Malades, Paris, France; and National Institute of Rheumatic Diseases, Piešťany, Slovakia and aimed to recruit 140 patients with alkaptonuria. In total, 70 patients were to be randomly assigned to receive 10 mg once daily oral nitisinone (Orfadin, Swedish Orphan Biovitrum, Stockholm, Sweden) and 70 to no treatment [The severity of the disease was established with the composite score cAKUSSI (or the clinical evaluation AKUSSI), which incorporates multiple clinically meaningful AKU symptoms (