Clinical trial NCT05164198: REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
Official title: Multicenter, Prospective Clinical Trial for Optimizing TNF Inhibitor Dose Adjustment in Ankylosing Spondylitis Patients With Stable Disease Activity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Axial Spondyloarthritis
Lead sponsor: Hanyang University Seoul Hospital
Sponsor class: OTHER
Collaborators: name: Linical Korea
First posted: 2021-12-20
Enrollment: 448
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 4, randomized, parallel, non-inferiority, open-label, multi-center clinical trial
Primary purpose: TREATMENT

Brief summary: Participants maintaining stable disease activity of Ankylosing Spondylitis (AS) with standard-dose tumor necrosis factor inhibitor (TNFi) treatment will randomly split into two groups: maintaining standard-dose TNFi, versus reduced-dose TNFi. The proportion of participants not underwent flare between the two groups will be analyzed.


Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of Ankylosing spondylitis (AS) and meet the modified New York classification criteria for AS.
* Subjects maintaining stable disease (Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] \< 4) with standard-dose subcutaneous tumor-necrosis factor inhibitor (TNFi) treatment during previous 6 months from screening.
* Ankylosing Spondylitis Disease Activity Score (ASDAS) \< 2.1 at screening and 12 weeks prior to screening
* In subjects treated with methotrexate or sulfasalazine, the dose should be maintained (methotrexate≤ 25mg/day, sulfasalazine ≤ 3 g/day) during previous 4 weeks before screening.
* In subjects treated with systemic glucocorticoids, the dose should be less than 10mg/day of predinisolone or equivalent during at least 2 weeks from the screening
* Subjects with stable dose of concomitant NSAID (including Cox2 inhibitors) during the 2 weeks from the randomization

Exclusion Criteria:

* Exposure to more than 1 TNFi
* History of hypersensitivity reaction to any TNFis
* Subjects with concomitant fibromyalgia, as determined by the investigator
* Subjects who have received any TNFis with reduced dosage
* Presence of total spinal ankylosis ('Bamboo spine')
* Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study
* Subjects with a history of malignancies and lymphoproliferative disorder including lymphoma within 5 years (Basal cell carcinoma treated within previous 3 months and showing no evidence of recurrence, actinic keratosis, and treated cervical/colon carcinoma in situ were allowed.)
* Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac or neurological disease, as determined by the investigator
* Subjects with significant laboratory abnormalities included but not limited to:

  1. AST/ALT \> 3.0 X ULN
  2. White blood cell (WBC) \< 3000/μL and/or absolute neutrophil count (ANC) \< 1500/μL
  3. Platelet count \<100,000/μL and/or hemoglobin level \<8.5 g/dL
  4. Serum creatinine ≥ 1.5 X ULN
* Subjected with any high-potency opioids (ex. methadone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, meperidine)
* Subjects with current acute or chronic viral hepatitis B or C or with human immunodeficiency virus (HIV) infection
* Subjects planning to receive any live attenuated vaccinations after screening
* Subjects has history of chronic alcohol abuse or drug abuse within 6 months from screening
* Subjects concomitantly treated with systemic glucocorticoid (\>10mg/day of prednisolone or equivalent doses)
* Subjects with any other condition that, in the Investigator's judgment, would make the subject unsuitable for inclusion in the study

Primary outcomes:
measure: Percentage of Participants who did not experience a flare
timeFrame: From week 0 to week 48
Secondary outcomes:
measure: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 12.
timeFrame: Week 12
measure: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 24.
timeFrame: Week 24
measure: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 36.
timeFrame: Week 36
measure: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 48.
timeFrame: Week 48
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 12.
timeFrame: Week 12
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 24.
timeFrame: Week 24
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 36.
timeFrame: Week 36
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 48.
timeFrame: Week 48
measure: Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 12.
timeFrame: Week 12
measure: Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 24.
timeFrame: Week 24
measure: Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 36.
timeFrame: Week 36
measure: Percentage of participants with Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at week 48.
timeFrame: Week 48
measure: Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 12.
timeFrame: Week 12
measure: Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 24.
timeFrame: Week 24
measure: Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 36.
timeFrame: Week 36
measure: Percentage of participants with Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at week 48.
timeFrame: Week 48
measure: Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 12.
timeFrame: Week 12
measure: Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 24.
timeFrame: Week 24
measure: Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 36.
timeFrame: Week 36
measure: Percentage of participants with Axial SpondyloArthritis International Society 5/6 Response Criteria (ASAS5/6) Response at week 48.
timeFrame: Week 48
measure: Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 12.
timeFrame: Week 12
measure: Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 24.
timeFrame: Week 24
measure: Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 36.
timeFrame: Week 36
measure: Percentage of participants with Axial SpondyloArthritis International Society Partial Remission Response Criteria (ASAS-PR) Response at week 48.
timeFrame: Week 48
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 12.
timeFrame: Week 12
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 24.
timeFrame: Week 24
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 36.
timeFrame: Week 36
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at week 48.
timeFrame: Week 48
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 24.
timeFrame: Week 24
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at week 48.
timeFrame: Week 48
measure: Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 24.
timeFrame: Week 24
measure: Change from baseline in Masstricht Ankylosing Spondylitis Enthesitis Score (MASES) at week 48.
timeFrame: Week 48
measure: Change from baseline in swollen/tender joint count (0-44) at week 24.
timeFrame: Week 24
measure: Change from baseline in swollen/tender joint count (0-44) at week 48.
timeFrame: Week 48
measure: Change from baseline in Erythrocyte sedimentation rate (ESR) at week 12.
timeFrame: Week 12
measure: Change from baseline in Erythrocyte sedimentation rate (ESR) at week 24.
timeFrame: Week 24
measure: Change from baseline in Erythrocyte sedimentation rate (ESR) at week 36.
timeFrame: Week 36
measure: Change from baseline in Erythrocyte sedimentation rate (ESR) at week 48.
timeFrame: Week 48
measure: Change from baseline in serum C-Reactive Protein (CRP) level at week 12.
timeFrame: Week 12
measure: Change from baseline in serum C-Reactive Protein (CRP) level at week 24.
timeFrame: Week 24
measure: Change from baseline in serum C-Reactive Protein (CRP) level at week 36.
timeFrame: Week 36
measure: Change from baseline in serum C-Reactive Protein (CRP) level at week 48.
timeFrame: Week 48
measure: Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 24.
timeFrame: Week 24
measure: Change from baseline in Assessment of SpondyloArthritis international Society (ASAS)-health index (ASAS-HI) at week 48.
timeFrame: Week 48
measure: Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 24.
timeFrame: Week 24
measure: Change from baseline in 5-level EQ-5D version (EQ-5D-5L) at week 48.
timeFrame: Week 48
measure: The amount of NSAID intake between week 0 and 12
timeFrame: From week 0 to week 12
measure: The amount of NSAID intake between week 12 and 24
timeFrame: From week 12 to week 24
measure: The amount of NSAID intake between week 24 and 36
timeFrame: From week 24 to week 36
measure: The amount of NSAID intake between week 36 and 48
timeFrame: From week 36 to week 48
measure: Percentage of patients at Least One Adverse Event (AE) During the study period.
timeFrame: From week 0 and week 48
Other outcomes:
Locations:
Study officials:
affiliation: Hanyang University
name: Tae-Hwan Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: