A multicenter, randomized, open-label, blinded-assessor, phase 4 study in patients with early rheumatoid arthritis to compare active conventional therapy versus three biologic treatments, and two de-escalation strategies in patients who respond to treatment.

A vizsgálat adatai

Ki végzi

Karolinska Institutet

Azonosító

NCT01491815EU 2024-516723-14-00

A regiszteradat frissítve

2024. december 30.

Eredeti leírás

The global aim of this study is to assess and compare 1) the proportion of subjects who achieve remission with active conventional therapy (ACT) versus three different biologic therapies; and 2) two alternative de-escalation strategies in patients who respond to first-line therapy.A teljes eredeti leírásKevesebb

The global aim of this study is to assess and compare 1) the proportion of subjects who achieve remission with active conventional therapy (ACT) versus three different biologic therapies; and 2) two alternative de-escalation strategies in patients who respond to first-line therapy.

Bevonási feltételek: Subject is ≥18 years of age; Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol; Subjects must be able and willing to self-administer s.c. injections or have a qualified person available to administer s.c. injections; Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria, 2010; <24 months from arthritis symptom debut (symptom duration will be registered); Subject must have DAS28 (CRP) > 3.2; ≥ 2 swollen joints AND ≥ 2 tender joints (based on 66/68 joint count); Subject must fulfill one of the following three criteria: RF positive OR ACPA positive OR CRP ≥10 mg/L; Female subject is either not of childbearing potential (postmenopausal, surgically sterile etc.), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion: • Intrauterine device (IUD) • Contraceptives (oral, parenteral, patch) for three months prior to study drug administration) • A vasectomized partner; Female subjects of childbearing potential must have a negative pregnancy test at the Screening visit; Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening.

Kizáró feltételek: Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases; Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the BL visit; Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication; Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed; Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study); Subject has been treated with any investigational drug within one month prior to screening visit; Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the study; Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis); Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease; Subjects will be evaluated for latent TB infection with a PPD or QuantiFERON test and X-ray. Subjects with evidence for latent TB will not be enrolled but first assessed according to local guidelines; Subject is known to have immune deficiency, history of Human Immunodeficiency Virus (HIV) or is otherwise severely immunocompromised; Subject has a history of clinically significant drug or alcohol usage in the last year; Current active inflammatory joint disease other than RA; Subject has a chronic widespread pain syndrome; Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs; Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks of screening; Screening clinical laboratory analyses show any of the following abnormal laboratory results: a. Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.75 times upper limit of normal (ULN). b. Positive serum human chorionic gonadotropin (hCG). c. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology indicative of current infection. d. Creatinine levels > 2x the ULN. If creatinine 1-2 times ULN, check GFR. e. Hemoglobin < 90 g/L. f. Absolute neutrophil count (ANC) < 1.5 x 10^3/uL. g. Serum total bilirubin ≥ 1.5 mg/dL (≥26 micromol/L); Subject has history of cancer or lymphoproliferative disease. Allowable exceptions: a. Successfully treated cutaneous squamous cell or basal cell carcinoma b. Localized carcinoma in situ of the cervix c. Curatively treated malignancy (treatment terminated) > 5 years prior to screening; Subject has chronic arthritis diagnosed before age 17 years; Men who are planning to father a child during the time they are included in the study; Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study; Subject is unwilling to comply with the study protocol; Subject has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.

ClinicalTrials.gov NCT01491815 · EU CTIS 2024-516723-14-00