Musculoskeletal Diseases
Conditions
Interventions
Placebo
Sponsors
AstraZeneca Pharmaceuticals Pty LTD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Informed Consent 1 Capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and CSP. 2 Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative (see Appendix D). Age 3 Are = 18 years of age at the time of signing the informed consent. Type of Participant and Disease Characteristics 4 Have a diagnosis of adult-onset RA as defined by the 2010 ACR/EULAR classification criteria for at least 12 weeks prior to Screening. 5 Have moderately-to-severely active RA as defined by: (a) = 6 Swollen Joints (SJC66) and = 6 Tender Joints (TJC68), attributable to RA, at Screening and confirmed prior to Randomisation. The distal interphalangeal joints should be evaluated but not included in the total joint counts to determine eligibility. AND (b) CRP > ULN per the central laboratory at Screening. 6 Have a positive result for ACPA at Screening. Prior Therapy 7 A history of inadequate response, or loss of response, or intolerance to: ? At least one csDMARD (methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine) treatment, AND/OR ? At least one and at most 2 TNFi (SC and/or IV, such as adalimumab, golimumab, certolizumab pegol, infliximab, etanercept, and ozoralizumab, originators or biosimilars). Concomitant Therapy 8 A history of at least 12 weeks treatment and = 4 weeks stable on a csDMARD and/or SC TNFi prior to the day of Randomisation (Day 1). The following therapies or their combinations (unless otherwise specified) are permitted during the study (lower maximum doses per local labelling are acceptable): (a) Oral or SC methotrexate up to 25 mg per week. Participants on methotrexate ought to be receiving folic acid as per local guidelines. (b) Oral leflunomide up to 20 mg per day (combination of methotrexate and leflunomide is not permitted). (c) Oral sulfasalazine up to 3000 mg daily dose. (d) Oral hydroxychloroquine up to 400 mg daily dose. (e) SC TNFi (including adalimumab, golimumab, certolizumab pegol, etanercept, and ozoralizumab, originator or biosimilar). Other SC TNFi may be considered after discussion with the AstraZeneca. (f) Combination of one csDMARD and a TNFi is permitted. 9 Participants taking oral corticosteroids (prednisolone = 10 mg daily or equivalent) must be on a stable dose = 4 weeks prior to the day of randomisation (Day 1).
Exclusion criteria
Exclusion criteria: Disease Characteristics 1 Stage IV RA (end-stage RA with extensive damage, deformity, and possible ankylosis of joints). 2 History or evidence of an alternate autoimmune or other condition that could confound the diagnosis of RA. These include systemic lupus erythematosus and other connective tissue disorders; seronegative arthropathies, such as psoriatic arthritis, axial spondyloarthropathy, and enteric arthropathy; gout; vasculitides; any arthritis with onset prior to age 17 years; and infectious arthropathy. Participants with RA and secondary Sjögren’s disease are eligible for the study. 3 Participants with a history of chronic pain syndromes (such as fibromyalgia) or osteoarthritis are excluded if they have active symptoms that will impact the assessment of efficacy in the study in the opinion of the Investigator. Prior/Concomitant Therapy 4 Currently receiving or have received any of the following therapies within 4 weeks of the day of Randomisation (Day 1): (a) Unstable dosing of csDMARDs (methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine), which is defined as a change in prescription. This also includes planned changes in dosing, including initiation or discontinuation. (b) Unstable dosing of oral corticosteroids (prednisolone or equivalent), which is defined as a change in prescription. This also includes planned changes in dosing, including initiation or discontinuation. (c) Ciclosporine, azathioprine, cyclophosphamide, gold, mycophenolate mofetil, tacrolimus, bucillamine, penicillamine or iguratimod. (d) Any opiate drug at an unstable dose, which includes planned increase, decrease, and new prescription during the study. (e) Chinese or traditional herbal therapies with confirmed or possible immunosuppressive potential. 5 Has been treated with intra-articular, IM, IV, trigger or tender point, intra-bursal, or intra-tendon sheath corticosteroids in the preceding 8 weeks prior to the day of Randomisation (Day 1). 6 Have received or planning to receive any bDMARDs/tsDMARDs (or biosimilars if applicable) beyond anti-TNF therapies for the treatment of RA, such as (a) Anti-IL-6R therapy (eg, tocilizumab and sarilumab) (b) Rituximab (c) Oral Januse kinase inhibitors (eg, upadactinib, baricitinib, tofacitinib, peficitinib, and filgotinib) (d) Abatacept (e) Anakinra (f) Investigational treatments 7 Have received infliximab within 12 weeks prior to the day of Randomisation (Day 1). 8 Receiving NSAIDs and acetaminophen/paracetamol daily (ie, not “as needed”) regimens where doses have not been stable = 1 week prior to the day of Randomisation (Day 1). 9 Have received Bacillus Calmette-Guérin vaccination or treatment < 52 weeks of Screening or received any other live vaccine (ie, live attenuated vaccine) < 12 weeks of Screening or intending to receive a live vaccine during the study. Infections 10 Evidence of recent or recurrent active infection within 4 weeks prior to day of Randomisation (Day 1), including use of parenteral or oral anti-infectives, such as antibiotics, antifungals, and antiprotozoals. Topical antimicrobials or antibiotics for an uncomplicated urinary tract infection may be eligible after discussion with the Study Sponsor. 11 Current or history of a serious opportunistic infection, such as pneumocystis, histoplasmosis, listeriosis, coccidiomycosis, cryptosporidiosis, and aspergillosis, within < 52 weeks of Screening. 12 Evidence of chronic HBV or HCV infection defined as: (a) HBV:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the clinical efficacy of AZD1163 as compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the clinical efficacy of AZD1163;To evaluate the clinical efficacy of AZD1163;To evaluate the PK of AZD1163;To evaluate the immunogenicity of AZD1163 | — |
Countries
South Africa
Contacts
Public ContactFatima Cassim
Astrazeneca Pharmaceuticals Pty Ltd
Outcome results
None listed