EAST-1 (ERAP-inhibition in Axial Spondyloarthritis Trial - 1)

Inclusion Criteria27

• Healthy Volunteers
• Healthy male and female subjects aged 18-55 years inclusive, at the Screening visit
• Participant must provide written informed consent to participate in the study
• Participant must be able and willing to comply with the requirements of the protocol (including dietary restrictions and exclusion of grapefruit juice)
• Male participants (and their female partners) / female participants must be willing to adhere to contraception requirements as detailed in the protocol
• Non-smokers or ex-smokers who have not smoked within the previous 6 months, as determined at the Screening visit
• Participant with a Body Mass Index (BMI) of 19-30. Body Mass Index = Body weight (kg) / \[Height (m)\]2
• AxSpA Participants
• Male or female, 18-65 years of age
• Participants diagnosed with Axial Spondyloarthritis, also fulfilling ASAS classification criteria including:
• HLA-B27 +ve (local testing)
• Objective evidence of inflammation at screening, specifically active sacroiliac joint inflammation on MRI fulfilling the ASAS MRI criteria (MRI+), assessed by the Principal Investigator or appropriately trained delegate, and/or elevated C-reactive protein (CRP+) ≥5.0mg/L.
• Symptom duration of ≥3 months
• Age at onset of active disease of \<40 years
• A score of ≥ 2.1 on the Ankylosing Spondylitis Disease Activity Score (ASDAS) on current treatment.
• At least one of the following:
• Current treatment with a NSAID, at a sufficient dose and following an appropriate dosing duration per local clinical guidelines, with inadequate clinical response OR
• Intolerance to ≥1 NSAID or contraindication(s) to NSAIDs
• Participants may have received 1 prior/(Australia only) 2 prior b/ts DMARD and discontinued due to intolerance or inadequate efficacy.
• Participants who have received 1/(Australia only) 2 prior treatments are required to undergo a washout at minimum:
• Biologic DMARDs 4 weeks or 5 half-lives prior to Day 1, whichever is longer.
• JAK inhibitor DMARDs 2 weeks prior to Day 1
• \- Participants with a score of ≥ 2.1 (High Disease Activity) on the Ankylosing Spondylitis Disease Activity Score (ASDAS) on current treatment.
• For study participants in Part B only:
• Objective evidence of inflammation may not be required for some participants with low to moderate disease activity.
• Participants with an ASDAS score between ≥1.3 and \< 2.1 (Low to Moderate Disease Activity) will require Sponsor approval prior to screening for the study, as they may not require an MRI to provide objective evidence of inflammation if on current treatment. For participants with low to moderate disease activity, MRI should only be performed if required to confirm ASAS classification.
• For axSpA participants in Part B, MRI assessment of the SI joints is only required for participant eligibility criteria evaluation to assess objective inflammation in case CRP measurement at baseline is negative and the objective evidence of inflammation is required.