| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active axial spondyloarthritis (axSpA) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Active axial spondyloarthritis (axSpA) |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10071400 |
| E.1.2 | Term | Axial spondyloarthritis |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10076297 |
| E.1.2 | Term | Non-radiographic axial spondyloarthritis |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate that the efficacy of a treat-to-target (T2T) approach (with secukinumab as first-line biologic) is superior to the standard-of-care (SOC) approach as measured by percentage of patients achieving an ASAS 40% response (ASAS40) at Week 24. |
|
| E.2.2 | Secondary objectives of the trial |
- the efficacy of the T2T approach is superior to SOC based on percentage of patients achieving ASAS40 at Week 12
- the efficacy of the T2T is superior to SOC based on percentage of patients achieving an ASDAS clinically important improvement/major improvement
- the efficacy of the T2T approach is superior to SOC based on percentage of patients achieving ASDAS < 1.3
- the efficacy of the T2T approach is superior to SOC based on percentage of patients achieving ASDAS < 2.1
- the efficacy of the T2T approach is superior to SOC based on percentage of patients achieving ASAS20, ASAS partial remission, and BASDAI50
- the T2T approach is superior to SOC in terms of improvement of disease activity, function, axial mobility, and quality of life measures according to: BASDAI, ASDAS, CRP and ESR, BASFI, BASMI and chest expansion, Global assessment of disease activity and general pain on VAS, ASAS-HI, SF-36, ASQoL, FACIT-Fatigue
- demonstrate overall safety and tolerability of secukinumab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 and spine 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. |
|
| E.4 | Principal 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 TNFα 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. Screening 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 immunodeficiency virus, hepatitis B or hepatitis C at randomization.
21. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
22. Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.
23. Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the trial.
24. Inability or unwillingness to undergo repeated venipuncture.
25. Any medical or psychiatric condition which, in the investigator’s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
26. Donation or loss of 400 mL or more of blood within 8 weeks before randomization.
27. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before randomization. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| ASAS 40% response (ASAS40) at Week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- ASAS40 at Week 12
- ASDAS clinically important improvement (defined as change from Baseline of ≥ 1.1)
- ASDAS major improvement (defined as change from BL of ≥ 2.0)
- percentage of patients achieving ASDAS < 1.3
- percentage of patients achieving ASDAS < 2.1
- percentage of patients achieving ASAS20, ASAS partial remission, and BASDAI50
- improvement of disease activity, function, axial mobility, and quality of life measures according to: BASDAI, ASDAS, CRP and ESR, BASFI, BASMI and chest expansion, Global assessment of disease activity and general pain on VAS, ASAS-HI, SF-36, ASQoL, FACIT-Fatigue
- overall safety and tolerability of secukinumab |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Standard-of-care treatment up to the maximum recommended dose at the discretion of the investigator |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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