Study in patients with active axial spondyloarthritis to assess efficacy of a treat-to-target treatment strategy with secukinumab compared to a standard-of-care treatment.

Phase 1

Conditions: Active axial spondyloarthritis (axSpA)
MedDRA version: 21.1Level: PTClassification code 10071400Term: Axial spondyloarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0Level: LLTClassification code 10076297Term: Non-radiographic axial spondyloarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2018-003882-32-DE

Lead Sponsor: ovartis Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 300

Inclusion Criteria

Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must provide written, signed and dated informed consent before any study assessment is performed.
2. Male or non-pregnant, non-lactating female patients at least 18 years of age.
3. Diagnosis of axSpA (either r-axSpA (AS) or nr-axSpA) fulfilling the ASAS classification criteria for axSpA (see Appendix 2 of main protocol).
4. Active disease as defined by having an ASDAS = 2.1 at Screening and Baseline despite concurrent NSAID therapy, or intolerance/contraindication to NSAIDs.
5. Objective signs of inflammation at Screening as defined by:
MRI of sacroiliac joints performed up to 3 months prior to screening showing acute inflammatory lesion(s), OR elevated quick CRP (> 5 mg/L), OR MRI showing acute inflammatory lesion(s) in the sacroiliac joints performed during screening period.
6. Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks (in total) in the past, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications.
7. Patients who are regularly taking NSAIDs (including cyclooxygenase-1 [COX-1] or cyclooxygenase-2 [COX-2] inhibitors) as part of their axSpA therapy are required to be on a stable dose for at least 1 week before randomization.
8. Patients taking methotrexate (MTX) 7.5 mg/week to 25 mg/week or sulfasalazine (= 3 g/day) are allowed to continue their medication but are required to be on a stable dose for at least 4 weeks before randomization.
9. Patients who are on a disease modifying anti-rheumatic drug (DMARD) other than MTX or sulfasalazine must discontinue the DMARD 4 weeks prior to randomization.
10. Patients taking corticosteroids must be on a stable dose of = 10 mg/day prednisone or equivalent for at least 2 weeks before randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process obtained within 3 months prior to Screening and evaluated by a qualified physician.
2. Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 or IL-17 receptor.
3. Patients who have previously been treated with TNFa inhibitors (investigational or approved).
4. Patients taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine).
5. Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g. CAMPATH, anti-CD3, anti-CD4, anti-CD5, anti-CD19).
6. History of hypersensitivity to secukinumab or adalimumab or their excipients or to drugs of similar chemical classes.
7. Contraindications for secukinumab or adalimumab.
8. Inability or unwillingness to undergo MRI (e.g. patients with pacemakers, aneurysm clips or metal fragments / foreign objects in the eyes, skin or body that are not MRI compatible) in case MRI is not already available (maximum 3 months old).
9. Use of any investigational agents within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to the Baseline Visit.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and minimum 16 weeks or longer if local label requires it after the last dose.
12. Active ongoing inflammatory diseases other than axSpA that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease or uveitis.
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
14. Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (= 160/95 mmHg), congestive heart failure (NYHA status of class III or IV) and uncontrolled diabetes.
15. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests such as AST, ALT, alkaline phosphatase or serum bilirubin.
16. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 µmol/L).
17. Laboratory results at screening visit: total white blood cell (WBC) count < 3000/µL, or platelets < 100 000/µL or neutrophils < 1500/µL or hemoglobin < 8.3 g/dL (83 g/L).
18. Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
19. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold test. Patients with a positive test may participate in the study if further work up establishes conclusively that the patient has no evidence of active TB. If presence of latent TB is established, then treatment according to local country guidelines must have been initiated prior to randomization.
20. Patients positive for human

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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