Ankylosing Spondylitis
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multi-center phase III clinical study to evaluate the efficacy and safety of AK111 in the treatment of subjects with active ankylosing spondylitis.
Detailed description
The study consists of 3 parts. Part 1 is screening period, Part 2 is Placebo control period and part 3 is Long term treatment follow-up period. The research period is 61 weeks in total.
Interventions
DRUGAK111
Drug: AK111 subcutaneous injection at week 0,1, 4 and 4-weekly thereafter until week 48.
DRUGPlacebo+AK111
Placebo+AK111 placebo subcutaneous injection at week 0,1, 4,8 and 12 follow AK111 4-weekly thereafter until week 48.
Sponsors
Akeso
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
* Male or female subjects aged ≥18 years old. * Subjects with confirmed ankylosing spondylitis before screening. * During screening and before randomization, BASDAI score ≥ 4, total back pain score≥ 4. * Subjects received at least 2 kind of non-steroidal anti-inflammatory drugs (NSAIDs), prior to randomization with an inadequate response or failure to respond, or with contraindications or intolerance to the use of NSAIDs. * Subjects who are regularly taking NSAIDs, weak opioids or oral glucocorticoids(The daily dose should be ≤10mg prednisone or equivalent dose of glucocorticoid) as part of their AS therapy are required to be on a stable dose for at least 14 days before randomization. If the drug has been discontinued, at least 2 weeks washout period is required before randomization. * Subjects taking methotrexate (MTX) (≤25mg/week) or Sulfasalazine (≤3g/day) are allowed to continue their medication if started at least 12 weeks prior to baseline, with a stable dose for at least 4 weeks before randomization. If the drug has been discontinued, at least 4 weeks washout period is required before randomization. * Subjects who are able to understand and voluntarily sign the ICF and complete the study procedure.
Exclusion criteria
* Subjects with symptom of pain that affected the evaluation of efficacy. * Subjects with other inflammatory diseases or autoimmune diseases except Ankylosing spondylitis (AS). * Subjects who are using strong opioid analgesics. * Received glucocorticoid intramuscular or intravenous injection within 2 weeks prior to randomization; Received intraarticular or paraspinal glucocorticoid therapy within 4 weeks before randomization. * Received other antirheumatic drugs (except methotrexate, sulfasalazine), proprietary Chinese medicine or traditional Chinese medicine decoction, JAK inhibitor treatment for AS within 4 weeks before randomization. * Received Natalizumab or other B cell or T cell modulator in the 12 months prior to randomization. * Previous exposure to secukinumab, ixekizumab or any other biologic drug directly targeting IL-17 or IL-17 receptor. * Received multiple tumor necrosis factor α (TNF-α) inhibitors; The eluting period of biologics received before randomization is shorter than the protocol. * Participated in a clinical study of any other drug or medical device within 1 month (≤30 days) prior to randomization, or last received the investigational drug within 5 half-lives. * The presence of any other systemic disease or laboratory abnormalities that the investigator has judged unsuitable for clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the response rate of ASAS20 | week 16 | Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The response rate of ASAS40 | week 16 | Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16. |
| The response rate of ASAS20 | baseline to week 52 | Percentage of subjects who achieve ASAS20 response throughout the clinical trial |
| The response rate of ASAS5/6 | baseline to week 52 | Percentage of subjects who achieve ≥20% improvement in five of the six domains (ASAS5/6) response throughout the clinical trial |
| Change from baseline on the ASDAS-CRP | baseline to week 52 | Change from baseline on the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) at each visit from baseline |
| Change from baseline on the SF-36 PCS | baseline, week 16 and week 52 | Change from baseline on the Short-Form 36 physical component score(SF-36 PCS) at each visit from baseline |
| Change from baseline on the ASQoL scores | baseline, week 16 and week 52 | Change from baseline on the Ankylosing Spondylitis Quality of Life (ASQoL) scores at each visit from baseline |
| Treatment-emergent adverse events | baseline to week 52 | Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study |
| Serious adverse events | baseline to week 52 | Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study |
| Clinically significant examination results | baseline to week 52 | Recording clinically significant examination results |
Countries
China
Outcome results
None listed