Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, AZD1163, placebo-controlled, double-blind, csDMARDs, TNFi, PAD2/4 inhibitor
Brief summary
Phase II study in participants with moderately-to-severely active rheumatoid Arthritis (RA) to evaluate efficacy and safety of AZD1163.
Detailed description
AZD1163 is a novel bispecific antibody that inhibits the activity of extracellular peptidyl arginine deiminase 2 (PAD2) and peptidyl arginine deiminase 4 (PAD4) enzymes, which are responsible for protein citrullination. In RA, citrullinated proteins lead to the production of pathogenic anti-citrullinated peptide antibodies (ACPA). This is a Phase II, randomised, double-blind, multicentre, 4 arm placebo-controlled study designed to evaluate the efficacy and safety of AZD1163 in ACPA + adults with moderate-to-severely active RA on standard of care (SoC) (conventional synthetic disease-modifying antirheumatic drugs \[csDMARDs\] or tumour necrosis factor inhibitor \[TNFi\] +/- csDMARD). The study will have a screening period followed by a randomisation period wherein approximately 320 participants will be randomised in a 1:1:1:1 ratio to receive study intervention. Participants will receive subcutaneous (SC) injection of one of three different doses of AZD1163 or placebo, along with SoC until Week 24 followed by a safety follow-up (FU) period of 28 weeks.
Interventions
DRUGAZD1163
Participants will receive SC injection of one of three different doses of AZD1163 in combination with SoC (csDMARD or TNFi +/- csDMARDSoC) until Week 24.
OTHERPlacebo
Participants will receive SC injection of placebo matched to AZD1163 in combination with SoC (csDMARD or TNFi +/- csDMARDSoC) until Week 24.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion * Diagnosed with adult-onset RA as defined by the 2010 ACR/EULAR classification criteria for at least 12 weeks prior to screening. * Moderately-to-severely active RA as defined by: a. \>= 6 swollen joints on 66SJC and \>= 6 tender joints on 68TJC; b. CRP \> upper limit of normal. * Have a positive ACPA at screening. * A history of inadequate response, or loss of response, or intolerance to: a. at least one csDMARD treatment, AND/OR b. At least one and at most 2 TNFi. * 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. * Exclusion * History or evidence of an alternate autoimmune or other condition that could confound the diagnosis of RA. Participants with RA and secondary Sjogren's disease are eligible. * Have received or planning to receive any biologic DMARDs (except for TNFi) or targeted synthetic DMARDs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score-C-Reactive Protein (DAS28-CRP) at Week 12 | Week 12 | Change from baseline in DAS28-CRP at Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology Response Criteria 20 (ACR20) at Week 12 | Week 12 | Proportion of participants achieving a 20% improvement in ACR response criteria at Week 12. |
| Percentage of Participants Achieving ACR50 at Week 12 | Week 12 | Proportion of participants achieving a 50% improvement in ACR response criteria at Week 12. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | Week 12 | Change from baseline in CDAI at Week 12. |
| Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | Week 12 | Change from baseline in SDAI at Week 12. |
| Summary statistics to evaluate the PK of AZD1163 | Week 0 to Week 24 and Follow-Up | AZD1163 concentrations in serum |
| Summary statistics to evaluate the immunogenicity of AZD1163 | Week 0 to Week 24 and Follow-Up | ADA (incidence, prevalence, and titres) |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, China, Germany, Hungary, Japan, Mexico, Poland, Puerto Rico, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed