Clinical trial NCT04345458: Safety and Efficacy Study of Prefilled Liquid Etanercept(Yisaipu) for Active Ankylosing Spondylitis
Official title: Safety and Efficacy of Prefilled Liquid Etanercept(Yisaipu) for Active Ankylosing Spondylitis on the Basis of NSAID Therapy: A Multicenter Randomized, Double-blind, Parallel Group Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Keywords: prefilled liquid etanercept
lyophilized etanercept powder
ankylosing spondylitis
Lead sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-14
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, double-blind, phase III parallel-group non-inferiority study aimed to investigate the efficacy and safety of prefilled liquid etanercept (Yisaipu) versus lyophilized etanercept powder (Yisaipu) in active ankylosing spondylitis patients.

Detailed description: The study carried out between March 6, 2014 and July 13, 2015 across multiple medical centers in China enrolled adult active ankylosing spondylitis patients aged between 18 and 65 years. Patients were randomized in a 3:1:1 ratio to receive twice weekly 25 mg prefilled liquid etanercept for totally 24 injections (group I) or once weekly 50 mg prefilled liquid etanercept for totally 48 injections (group II), or 25 mg twice weekly lyophilized etanercept powder for totally 48 injections (group III). The primary efficacy outcome was the proportion of patients who achieved ASAS20 at week 24.

Eligibility criteria: Inclusion Criteria:

* age 18-65，male or female
* Sign the informed consent
* Fulfill the 1966 AS New York criteria for axial spondyloarthritis(SpA)
* Active disease phase of SpA, defined as BASDAI≥4 or night back pain≥4 at screening
* Inadequate response to NSAID≥4 week
* Application of NSAID with stable dose for no less than 2 weeks at screening
* Stable dose of prenisone for at least four weeks at ≤10mg per day if used at screening, or stop oral use for at least 4 weeks or stop local injection at least 12 weeks
* Stable dose of any DMARD for at least four weeks if used at screening, or stop use for at least 4 weeks
* Stop and receiving washing out for at least 4 week if receiving Chinese traditional drug for AS, physical treatment, vaccication or IVIG
* Stop and receiving washing out for at least 12 week if receiving other biologics or other drug trials
* The lab exam should achieve the criteria as below
* Hb≥85g/L, 3.5×109/L≤WBC count≤10×109/L, PLT≥ lower limit of normal range, ALT≤2 fold of upper limit of normal range, serum creatine ≤upper limit of normal range. Negative pregnacy test for female patients. And promise to carry out contraception during the trial and 6 weeks after the trial is ended

Exclusion Criteria:

* Allergic condition or Allergic to IgG or any element of Yisaipu®
* Clinical or radiographic evidence of Complete ankylosis of spine
* Previous receiving TNF-a blockers therapy ≥3 months with poor response
* Achieve any following tuberculosis criteria

  1. History of active tubercolosis, or radiographic evidence of present or previous history of pulmonary tubercolosis
  2. close contact with patients with tubercolosis, or with high risk of infection of tubercolosis such as immune suppression status
  3. Strong positive of PPD skin test with diameter ≥10mm. at screen or within 3 weeks prior to screen
* Presence of acute infection or acute onset of chronic infection at screen
* Invasive fungal infection or conditional infection within 6 months prior to screen
* HBS-Ag or HBC-Ab positive at screen or history of HBS/HBC infection
* History of infection on artifitial joints
* Organ transplantation surgery within 6 months prior to screen
* Presence of other autoimmune diseases, including IBD, psoriasis, uveitis, SLE, multiple sclerosis, etc.
* History of congestive heart failure
* History of malignancies within 5 years prior to screen, excluding complete resection of squamous cell carcinoma, or basal cell carcinoma or cervical carcinoma in situ.
* AIDS or HIV infection
* History of lymphoma or lymphoproliferative disorders
* Presence of serious disorder of important organs or system
* Presence of factors which may influence the compliance

Primary outcomes:
measure: the proportion of patients who achieved ASAS20
timeFrame: at week 24
Secondary outcomes:
measure: the proportion of patients who achieved ASAS40, ASAS partial remission
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved ASAS 5/6
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved the ASDAS clinically important and major improvement and inactive disease
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved BASDAI50
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in BASDAI
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in BASFI
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in BASMI scores
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in nocturnal back pain and total back pain VAS
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in patient global assessment and physician global assessment
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in number of swollen joints and number of tender joints
timeFrame: at weeks 12 and 24
measure: the proportion of patients who achieved improvement in ESR and CRP
timeFrame: at weeks 12 and 24
Other outcomes:
measure: AEs
timeFrame: at weeks 2, 4, 8, 12, 16, 20 and 24
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital clinical trial center
state: Beijing
Study officials:
References:
citation: Zhao D, He D, Bi L, Wu H, Liu Y, Wu Z, Li Y, Wang G, Li X, Bao C, Jiang L, Zhang Z, Xiao W, Tong G, Wang D, Huang F. Safety and Efficacy of Prefilled Liquid Etanercept-Biosimilar Yisaipu for Active Ankylosing Spondylitis: A Multi-Center Phase III Trial. Rheumatol Ther. 2021 Mar;8(1):361-374. doi: 10.1007/s40744-021-00276-1. Epub 2021 Feb 9.