M13-549 Phase 3 JAK study csDMARD subjects with Moderate to Severe RA
Research type
Research Study
Full title
A Phase 3, Randomized, Double-Blind Study Comparing ABT-494 to Placebo in Subjects with Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs
IRAS ID
192903
Contact name
Christopher Edwards
Contact email
Sponsor organisation
AbbVie Deutschland GmbH & Co.KG
Eudract number
2015-003332-13
Duration of Study in the UK
1 years, 11 months, 18 days
Research summary
Summary of Research
Rheumatoid arthritis (RA) is a long-lasting disease that is caused by an abnormal immune response predominantly affecting the joints. Currently patients have a range of options for treatment but these do not always have the desired or prolonged effect over the length of a patient’s life. This study is for patients who have moderate to severely active RA and are on stable conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) but have had an inadequate response to csDMARDs. The study is comparing ABT-494, an investigational drug, at two doses, high and low, with a placebo comparator whilst on a stable csDMARD background to assess its safety, efficacy and tolerability. This study will include approximately 600 subjects in 230 sites globally.
Each patient will undergo a screening process up to a maximum of 35 days followed by a 24 week treatment phase, with 9 clinic visits, for which the patient is randomly assigned to one of 4 treatment courses; this is blinded from all involved throughout the study. The treatment courses are for ABT-494 at a high dose (one third of the patients assigned to this arm) and low dose (one third of patients assigned) and 2 placebo comparison treatment courses. The placebo treatment will stop after 12 weeks for both courses, patients on one course will be transferred to the high dose (one sixth of patients assigned) and the other to the low dose of ABT-494 (one sixth of patients assigned). There is one post-treatment follow up visit after 30 days for those subjects who prematurely discontinue OR complete the study and do NOT enter the blinded extension. If they wish to continue or start to receive the ABT-494 medication following the treatment period, whichever arm they are on, the patient will have the option to continue into an extension study.
Summary of Results
Rheumatoid arthritis (RA) is an autoimmune disease that causes the body’s immune system to attack itself. • RA targets the body’s joints, causing inflammation (swelling, pain, and redness). These symptoms can disappear and return. • In this study, doctors tested a medicine called upadacitinib and compared it to placebo (looks like study treatment but contains no medicine) in patients with moderate to severe RA who had not responded to, or could not tolerate, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). • This study took place from December 2015 to March 2022 in 35 countries. • At the start of the study, patients were randomly (by chance) put into groups that determined what treatment they would receive in Part 1 and Part 2. • In Part 1, patients received one of two doses of upadacitinib or placebo for 12 weeks. • In Part 2, patients received upadacitinib higher dose or upadacitinib lower dose. • The main goal of the study was to see if patients with moderate to severe RA had improvement in their RA symptoms after 12 weeks of treatment (Part 1) with one of two different doses of upadacitinib or placebo. • Improvement in symptoms was based on the American College of Rheumatology Criteria (ACR), and the Disease Activity Score-28 with C-reactive protein (DAS28 [CRP]). • This study showed that after 12 weeks of treatment, patients treated with upadacitinib had greater improvement in RA symptoms compared to patients treated with placebo. • 22.2% of patients in Part 1 and 57.6% of patients in Part 2 had side effects. Side effects are unwanted medical events considered by the study doctors to be at least possibly related to the study treatment. • The most common side effects in Part 1 were nausea, upper respiratory tract infection (infection in the lungs and upper airways), and headache. • The most common side effects in Part 2 were shingles (a painful blistering rash caused by a virus), upper respiratory tract infection, and urinary tract infection (infection of the kidney and/or bladder, also called a UTI). • The results of this study will be used by researchers to further develop upadacitinib. • If you participated in this study and have questions about your individual care, contact the doctor or staff at your study site.
Available at: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQHvPHxRsI5n4yUVVAkKgTsl8Kf8-2FjIIk4dojZz9Q-2FRdvESEilqKsLcIlrX0tYGFZ2jbe5zsXZ8HHTFLS-2FWQkxszBO-2Fmv8SZ1Wmc2uSBQXkBs1xmzSpvOYmeTBK3knvwyYzEDHvIvZ0nSUZu8JzYfl-2BpwFOtcKuBcCjYhFEm6HNNqAImsTEiMPRhOKcIAkg7-2FN-2B9uMZQHjkU0h8QzmN1IzWYpCW1CdV7tNRRJx-2BQbVSMGI3vPV1t20EhD4HAG3Ek7baIKHB8zhDo0Wkn3BXIKcc1kXBMU8-2FLFf-2Be485uhyl5hpN1zIYgP4xlJaH-2BQBkWqWWw65Z6G2KEFHE2F4JblaJYNN80EfEq1LQ-2FfcdG-2F5g58rtB3c-2Bb82xZRdYFqWCNuWO9-2BY81UMuj5IWN-2F3r74Jn3geCQ0dN4oT14P2b9gg623kStiag0LYrRm6vPD9lrla3IiZxQOLJMBr0KJ4HkR9bgpW1FKXP-2Byu-2Fg-2Bom3-2FybsRtQ3b-2Bcqp-2BeFyPP9NbBc2QehVTRAxzIsxXZgeM5LCcm6cz3DTP3Jizo5zETK9t3noSZf7SHzBtRKaLB2Qj616Ph98aYfU0xkT7QfRfvPPSWKjXX7eWeI8SfXKHeHSfcl2hz-2FdB4ZPaD4Dk1ZeWcJO9tC9fOgnacYpH-2B2Qp-2BOKjSzGpqqRsvvWHBVKw9Y8gZuv31I7iES1AB7ryUx0hWA3xrFpN-2F8gTRuqKE0wVqeTCs-3D_fEQ_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJcAwu7oY9xnuASWLfEdCWpqjyVjwdQ0IPqQ4C6VqJIWkaV1BlzNX-2Bar6dOKqUW4lpFBBv6QVJE0Vfllu2-2FSpXsoVee2slxbwLuFfnPRG6sJp-2FQa1P4gDLH9lJx-2Bj8d2kum9nEbwU0LmJnex2TQMv3HvGyjCZl-2FRMM7NVgD36Mp9g-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C159130d3c6514c0ca13d08db4593b7b9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638180272960444062%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=tK8okprbHUNH0w1iSsURNHM9gwEl7PEq5sUFrO2qlrA%3D&reserved=0
REC name
South Central - Oxford B Research Ethics Committee
REC reference
15/SC/0699
Date of REC Opinion
25 Jan 2016
REC opinion
Further Information Favourable Opinion