REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)

NCT05164198 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: HC21C0076
• Study Type: interventional
• Target: 448
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ankylosing Spondylitis; Axial Spondyloarthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants who did not experience a flare

  Flare is defined as below: * A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥ 2.1) at 2 consecutive visits or an ASDAS greater than (\> 3.5) at any visit. * If a participant had an ASDAS ≥ 2.1 and ≤ 3.5, the participant has an additional visit 4 weeks later and ASDAS is assessed by the investigator to confirm the flare. The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm \[ln\] of the (CRP \[mg/L\] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Higher scores mean a worse outcome in the all following components.

  From week 0 to week 48

Secondary Outcomes (51)

• Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 12.

  Week 12

• Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 24.

  Week 24

• Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 36.

  Week 36

• Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 48.

  Week 48

• Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at week 12.

  Week 12

Study Arms (2)

Open-label reduced-dose TNFi

EXPERIMENTAL

Participants in the experimental arm will receive one of the intervention below according to the TNFi agent used at baseline: 1. Adalimumab 40mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48. 2. Etanercept 50mg subcutaneous every 10 days (Q10D) from week 0 to week 48. 3. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 5 weeks (Q5W) from week 0 to week 48. 4. Remsima SC 120mg subcutaneous every 3 weeks (Q3W) from week 0 to week 48.

Biological: Adalimumab and its biosimilars; Biological: Biological: Etanercept and its biosimilars; Biological: Golimumab; Biological: Infliximab biosimilar

Open-label full-dose TNFi

ACTIVE COMPARATOR

Participants in the comparator arm will receive one of the intervention below according to the TNFi agent used at baseline: 1. Adalimumab 40mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48. 2. Etanercept 50mg subcutaneous every week (QW) from week 0 to week 48. 3. Golimumab 50mg (100mg if a participant's body weight ≥ 100kg) subcutaneous every 4 weeks (Q4W) from week 0 to week 48. 4. Remsima SC 120mg subcutaneous every 2 weeks (Q2W) from week 0 to week 48.

Biological: Adalimumab and its biosimilars; Biological: Biological: Etanercept and its biosimilars; Biological: Golimumab; Biological: Infliximab biosimilar

Interventions

Adalimumab and its biosimilars BIOLOGICAL

1. Active substance: Adalimumab 2. Pharmaceutical form: Prefilled syringe 3. Concentration: 100mg/mL 4. Route of administration: Subcutaneous injection

Also known as: Humira, Adaloce

Open-label full-dose TNFi; Open-label reduced-dose TNFi

Biological: Etanercept and its biosimilars BIOLOGICAL

1. Active substance: Etanercept 2. Pharmaceutical form: Prefilled syringe 3. Concentration: 50mg/mL 4. Route of administration: Subcutaneous injection

Also known as: Enbrel, Eucept, Etalace

Open-label full-dose TNFi; Open-label reduced-dose TNFi

Golimumab BIOLOGICAL

1. Active substance: Adalimumab 2. Pharmaceutical form: Prefilled syringe 3. Concentration: 100mg/mL 4. Route of administration: Subcutaneous injection

Also known as: Simponi

Open-label full-dose TNFi; Open-label reduced-dose TNFi

Infliximab biosimilar BIOLOGICAL

1. Active substance: Infliximab 2. Pharmaceutical form: Prefilled syringe 3. Concentration: 120mg/mL 4. Route of administration: Subcutaneous injection

Also known as: Remsima

Open-label full-dose TNFi; Open-label reduced-dose TNFi

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• AST/ALT \> 3.0 X ULN
• White blood cell (WBC) \< 3000/μL and/or absolute neutrophil count (ANC) \< 1500/μL
• Platelet count \<100,000/μL and/or hemoglobin level \<8.5 g/dL
• 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

Sponsors & Collaborators

• Hanyang University Seoul Hospital: lead
• Linical Korea: collaborator

MeSH Terms

Conditions

Spondylitis, Ankylosing; Axial Spondyloarthritis

Interventions

Adalimumab; Etanercept; golimumab; CT-P13

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Tae-Hwan Kim, MD, PhD

  Hanyang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tae-Hwan Kim, MD, PhD

CONTACT

82-2-2290-9245; thkim@hanyang.ac.kr

Ji Hui Shin

CONTACT

82-2-2290-9252; joobaraki77@naver.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 4, randomized, parallel, non-inferiority, open-label, multi-center clinical trial

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: December 20, 2021
• Study Start: January 15, 2022
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: December 20, 2021

Record last verified: 2021-10