Adult active ankylosing spondylitis
Conditions
Interventions
Test group :QX002N 160mg Q4W
Control group :Placebo Q4W
Sponsors
Peking Union Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criterias to be eligible for admission to the study. (1) Patients voluntarily participate in the study, understand and sign the informed consent form (ICF). (2) The age of patient signing the ICF is 18-70 years old (including the threshold). Male or female. (3) Patients meet the modified New York criteria for AS (mNY) of 1984 to be diagnosed with AS, and the age of onset <45 years old. The mNY standard is: ? Low back pain lasting at least 3 months and improving with activity but not with rest; ? The lumbar spine has limited movement in the sagittal (anteroposterior) and frontal (lateral flexion) planes; ? The thoracic dilatation range is less than normal for peers and gender; ? Bilateral grade II to IV or unilateral grade III to IV sacroiliac arthritis. The patients meeting ? and any one of ?~? can be diagnosed as AS. (4) Active AS was diagnosed at screening and before randomization. Activity AS was defined as: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was = 4 and the spinal pain score (NRS Question 1 for spinal pain intensity assessment) was = 4. (5) Patients must meet at least one of the following criteria: poor response to therapeutic doses of non-steroidal anti-inflammatory drugs (NSAIDs), intolerance, or contraindications to NSAIDs treatment. Poor efficacy of therapeutic dose NSAIDs was defined as =4 weeks of treatment with one NSAIDs before screening or =2 weeks of treatment with each NSAIDs without remission of symptoms. Patients taking NSAIDs for AS on a regular basis were required to stabilize the dose for at least 2 weeks prior to randomization, and only dose reduction or discontinuation due to adverse events (such as gastrointestinal reactions) was permitted during the study period, and no replacement of NSAIDs was permitted. (6) Patients received =1 TNF-a inhibitor before screening. In patients who had received a TNF-a inhibitor, the inhibitor was discontinued at a therapeutic dose with no relief of symptoms or drug intolerance (defined as a patient who was determined by the investigator to be insufficiently responsive to or intolerant to a TNF-a inhibitor sustained at a therapeutic dose for =12 weeks). Patients who have previously been on a TNF-a inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization:: ? Etanercept: 4 weeks ? Infliximab: 8 weeks ? Adalimumab: 10 weeks ? Golimumab: 10 weeks ? Certolizumab: 10 weeks ? Recombinant human tumor necrosis factor receptor type II antibody fusion protein for injection: 4 weeks If patients cannot complete the wash-out during the screening period, they could receive a re-screening after self-cleaning outside the study. (7) Fertile patients (male and female) agree to use a reliable contraceptive method (abstinence, prior ligation, hormonal and/or barrier method) during the trial period and for at least 6 months after the end of study treatment; Blood human chorionic gonadotropin (hCG) pregnancy test results must be negative in fertile women within 1 day prior to administration; Male patients cannot donate sperm during the trial and for six months after the end of the study treatment. (8) The patients can communicate well with the investigator and complete the study according to the clinical protocol.
Exclusion criteria
Exclusion criteria: Patients cannot participate in this study if they meet any of the following criteria. (1) The spine is completely rigid. (2) Other systemic inflammatory diseases (including but not limited to systemic lupus erythematosus, vasculitis, rheumatoid arthritis, etc.) or other chronic pain diseases (including but not limited to fibromyalgia, etc.) at the time of screening, or other diseases that the investigators determined might interfere with the evaluation of drug effectiveness. Patients with mild psoriasis who have never received and are assessed not to require systemic treatment for psoriasis may be enrolled if they meet the remaining eligibility criteria. (3) Other active inflammatory diseases at the time of screening (including but not limited to active Crohn's disease, active ulcerative colitis, or other active inflammatory bowel disease). Those who had no disease progression for at least 6 months prior to signing the ICF, were currently receiving treatment, and were on stable treatment for at least 6 months prior to signing the ICF, being eligible for enrollment. (4) Active uveitis (acute onset) was present for 4 weeks before signing the ICF. Only one additional screening should be performed after =4 weeks of resolution of acute attacks. (5) There were myocardial infarction, moderate to severe congestive heart failure (New York Heart Association Class III or IV), new ischemic heart disease, percutaneous intracavitary coronary angioplasty, coronary artery bypass grafting, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack in the 12 weeks prior to screening. Or screening for major uncontrolled cardiovascular and cerebrovascular events that the investigator believes would place the patient at unacceptable risk or significantly interfere with the trial results. (6) Screening patients with a history of malignant tumors (excluding skin squamous cell carcinoma, basal cell carcinoma, and cervical carcinoma in situ, which have been successfully treated and patients survived for more than 5 years without evidence of recurrence). (7) A history of lymphoproliferative disease (including lymphoma or signs or symptoms of lymphoproliferative disease at any time) in the 5 years prior to screening. (8) Patients with a history of opportunistic infection within 6 months prior to screening (cytomegalovirus, mycoplasma, pneumocystis carinii, histoplasmosis, candida, Aspergillus, mycobacterium other than tuberculosis, etc.). Or patients with a history of herpes zoster or significant varicella-zoster infection within 3 months prior to screening. (9) A history of chronic infections (such as chronic kidney infections). A serious or life-threatening infection within the 6 months prior to screening (such as: Hepatitis, pneumonia, pyelonephritis, etc.). Or any current symptoms or signs indicating possible infection (such as fever, cough, urgency to urinate, pain in urine, abdominal pain, diarrhea, skin infection wounds, etc.). The above symptoms caused by upper respiratory tract infection can be rescreened after recovery. (10) Patients at high risk of infection at the time of screening (such as leg ulcers, indwelling catheters, persistent or recurrent chest infections, and those who are bedridden or wheelchair-bound for long periods of time). (11) Patients had any major surgery in the 6 months prior to randomization. This includes, but is not limited to, spinal surgery, joint surgery, or major surgery to be undergone d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving the International Association for the Assessment of Spinal Arthritis(ASAS)40 at week 16; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving ASAS40 at weeks 4, 8, and 12;Proportion of subjects achieving ASAS20 at weeks 4, 8, 12 and 16;Proportion of subjects achieving ASAS partial remission at weeks 4, 8, 12, and 16;Proportion of subjects achieving ASAS 5/6 at weeks 4, 8, 12, and 16;Changes in ASDAS compared to baseline at weeks 4, 8, 12, and 16;Proportion of subjects with ASDAS inactive disease at weeks 4, 8, 12, and 16;Proportion of subjects reaching BASDAI50 at weeks 4, 8, 12, and 16;Changes in BASDAI compared to baseline at weeks 4, 8, 12, and 16;Changes in BASFI compared to baseline at weeks 4, 8, 12, and 16.;Changes in BASMI compared to baseline at weeks 4, 8, 12, and 16;Changes in SF-36 compared to baseline at weeks 4, 8, 12, and 16;Changes in ASQoL compared to baseline at weeks 4, 8, 12, and 16;Changes in PGA compared to baseline at weeks 4, 8, 12, and 16;Changes in PhGA compared to baseline at weeks 4, 8, 12, and 16;Changes in MASES scores compared to baseline at weeks 4, 8, 12, and 16;Proportion of subjects achieving ASAS40 at weeks 20, 28, 36, 44 and 52;Proportion of subjects achieving ASAS20 at weeks 20, 28, 36, 44 and 52;Proportion of subjects achieving ASAS partial remission at weeks 20, 28, 36, 44 and 52;Proportion of subjects achieving ASAS 5/6 at weeks 20, 28, 36, 44 and 52;Changes in ASDAS compared to baseline at weeks 20, 28, 36, 44 and 52;Proportion of subjects with ASDAS inactive disease at weeks 20, 28, 36, 44 and 52;Proportion of subjects reaching BASDAI50 at weeks 20, 28, 36, 44 and 52;Changes in BASDAI compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in BASFI compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in BASMI compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in SF-36 compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in ASQoL compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in PGA compared to baseline at weeks 20, 28, 36, 44 and 52;Changes in PhGA compared to baseline at weeks 20, 28, 36, 4 | — |
Countries
China
Contacts
Public ContactZeng Xiaofeng
Peking Union Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed