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

Ki vehet részt

• 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 2009 ASAS classification criteria including:; HLA-B27 +ve (local testing); Objective evidence of inflammation at screening, defined as 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
• Part B only : MRI assessed by the Principal Investigator or appropriately trained delegate
• Part D: MRI confirmed by a central imaging reader
• A score of ≥ 2.1 on the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on CRP; At least one of the following:
• Current treatment with a NSAID, at an adequate dose and duration per local clinical guidelines, with inadequate clinical response OR
• Intolerance to ≥1 NSAID or contraindication(s) to NSAIDs
• Participants who are eligible to receive biologic or target synthetic disease modifying antirheumatic drugs (b/tsDMARDS) (as defined by local regulatory and reimbursement criteria) must have been offered available therapies and declined treatment at this time; Participants may have received one or two prior b/tsDMARDs and discontinued due to intolerance or inadequate efficacy, provided that:
• Part B: Participants who have received two prior b/ts DMARDs require Sponsor confirmation prior to screening; Part D: Participants with prior b/tsDMARD treatment will be capped; Participants who have received prior b/tsDMARDs treatment(s) are required to undergo a washout period at minimum:
• Biologic DMARDs - 4 weeks or five half-lives prior to Day 1, whichever is longer
• JAK inhibitor DMARDs - 2 weeks prior to Day 1
• Participants must be GRWD0715 naïve
• Part C only: Participants enrolling into Part C (any rollover arm) must:
• Have completed Part B treatment per protocol or, if entering from Part D, have completed Part D treatment per protocol and have received placebo
• Have not permanently discontinued GRWD0715 due to safety concerns
• Have no ongoing safety issues that, per protocol or in the opinion of the Investigator, would preclude further treatment
• Provide written informed consent to participate in Part C
• Participants must commit to and/or continue to comply with the contraception requirements described in the study protocol

Ki nem vehet részt

• Participation in a New Chemical Entity clinical study within the previous 124 days or a marketed drug clinical study within the previous 93 days
• Participants previously treated with three or more b/tsDMARDs
• Participants not meeting the required washout period for any b/tsDMARD exposure prior to re-entry into Part C
• Known infection or lifestyle risk factors for human immunodeficiency virus (HIV) and/or hepatitis B or C infection, as determined at the Screening visit; AxSpA Participants
• History or presence of any clinically significant findings in medical history, physical examination, vital signs and/or laboratory tests that, in the opinion of the Investigator, would preclude inclusion in the study
• Inadequate Haematologic function, defined as:; Haemoglobin <10 g/dL; Absolute white blood cell count <3.0 x 109 /L (<3000 mm3); Absolute neutrophil count <1.2 x 109 /L (<1200 mm3); Absolute lymphocyte count <1.0 x 109 /L (<1000 mm3); Platelet count <100 x 109 /L (<100.000 mm3); Inadequate renal function, defined as estimated Creatinine Clearance <40mL/min based on Cockroft Gault equations at screening; Inadequate liver function, defined as; total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal at screening visit. For subjects with Gilberts syndrome, upper limit of normal for total bilirubin will be 2.9mg/dl; History of any other autoimmune rheumatic disease (e.g., psoriatic arthropathy, systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymositis) or known diagnosis of fibromyalgia; Active or symptomatic psoriasis. Participants with a previous history of or currently stable psoriasis are eligible; Active or symptomatic inflammatory bowel disease (IBD). Participants with a history of IBD are allowed to participate; Screening 12-lead ECG demonstrating clinically relevant abnormalities which may affect participant safety; Presence of active anterior uveitis (AAU). Participants with a history of, or currently stable AAU are eligible; Participants who require prohibited concomitant medications; Part C Immediate Rollover:; For Immediate Rollover participants, all eligibility requirements are accounted for within the Part C Inclusion Criteria, and participants that have ongoing safety issues that, in the opinion of the investigator would preclude continued treatment, are excluded
• Healthy Volunteers
• Part C only Returning Rollover and Placebo Rollover: