Clinical trial NCT06048224: Phase III Clinical Trial Comparing the Safety, Efficacy, and Immunogenicity of Recombinant Anti-interleukin-6 Receptor Humanized Monoclonal Antibody Injection in Combination With Methotrexate and Jamelor ® in the Treatment of Moderate to Severe Rheumatoid Arthritis
Official title: A Randomized Controlled, Double-blind, Phase III, Multicenter Clinical Study of HS628 Versus Actemra® in Combination With Methotrexate as Therapy in Patients With Moderate to Severe Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate to Severe Active Rheumatoid Arthritis
Lead sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 669
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of intravenous HS628 in combination with MTX versus Actemra in combination with MTX, in participants with moderate to severe active rheumatoid arthritis (RA) who have inadequate response to current MTX therapy. The study comprises a 24-week treatment phase, followed by a 4-week safety observation period.


Eligibility criteria: * Inclusion Criteria:

  1. the person who has signed the informed consent and can complete the test according to the program;
  2. age ≥18 years old and ≤75 years old (subject to the date of signing the informed consent), male or female;
  3. weight ≥30kg;
  4. according to the 2010 ACR/EULAR diagnostic criteria, rheumatoid arthritis was diagnosed with the disease duration ≥ 6 months;
  5. swelling and tenderness joint count ≥ 6 (based on 66 joint counts) and tenderness joint count ≥ 6 (based on 68 joint counts) during the screening period, if both swelling and tenderness are present in the same joint, the joint shall be included in both swelling and tenderness joint count (excluding artificial joints);
  6. C-reactive protein (CRP) ≥10mg/L or erythrocyte sedimentation rate (ESR) \> 28mm/hr at the screening stage;
  7. patinents who had received DMARD treatment for at least 3 months before screening visit;
  8. Inadequate response to previous or current methotrexate treatment;
  9. patients who received at least 12 weeks of oral methotrexate treatment (≥ 7.5mg/week) and at least 4 weeks of stable oral dose (methotrexate dose 7.5-25mg/week, with critical value) before random administration;
  10. all non-biological agents DMARD except methotrexate should be discontinued for at least 2 weeks before random administration( In addition, leflunomide should be discontinued for ≥8 weeks, and at least 2 weeks before randomized administration if standard coletenide therapy or activated carbon elution has been followed; Discontinuation of sulfasalazine ≥4 weeks; Yunke withdrawal ≥12 weeks）;
  11. Patinents who will receive oral folic acid treatment (at least 5 mg/ week or a dose determined according to local medical practice) or an equivalent drug (a combination of drugs required for MTX treatment) throughout the study, and the dose of folic acid or an equivalent drug was stable for at least 2 weeks prior to random administration.
  12. biologic DMARD should have been discontinued for at least 2 weeks prior to random administration.For example, adamumab, setuzumab, infliximab and golimumab should be discontinued for ≥8 weeks.Etanercept (enley, esipher, and jeanke), Anbainuo should be discontinued for ≥ 4 weeks;Tofetib and baritinib should be discontinued for ≥2 weeks;
  13. any Chinese herbal medicine, proprietary Chinese medicine or natural medicine for the treatment of RA has been discontinued for at least 2 weeks before random administration;
  14. any non-steroidal anti-inflammatory drug must be given at a stable dose for at least 2 weeks prior to random administration;
  15. at the time of screening, if the subject was taking prednisone or a comparable dose of glucocorticoid, the prerandomized stable dose (prednisone dose ≤10mg/ day) was administered for at least 4 weeks;
  16. Non-lactating women and non-pregnant women (negative blood pregnancy test for women of childbearing age; the subject or his or her spouse will use appropriate and effective contraceptive methods, such as abstinence, oral contraceptives, Iuds, or double barrier methods, during the trial period and for 3 months after the end of the last dose.
* Exclusion Criteria:

  1. Subjects have previously received Tocilizumab treatment or are allergic to any component of Tocilizumab (or investigational drug product);
  2. Subjects with long-term bedridden/wheelchair;
  3. Subjects with inflammatory joint disease other than rheumatoid arthritis in their previous or current medical history; or other systemic autoimmune diseases;
  4. Current symptoms of severe, progressive or uncontrolled diseases of renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral. Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study;
  5. Subjects with history of severe hypersensitivity or anaphylaxis to human, humanized or mouse monoclonal antibodies.

Primary outcomes:
measure: Proportion of patients with an ACR20 response
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of patients with an ACR50, 70 response
timeFrame: Week 24
measure: Proportion of patients with an ACR20, 50, 70 response
timeFrame: Week 12
measure: Proportion of patients with DAS28 (ESP、CRP) ≤3.2 and <2.6
timeFrame: Week 12
measure: Proportion of patients with DAS28 (ESP、CRP) ≤3.2 and <2.6
timeFrame: Week 24
measure: Simplified Disease Activity Index (SDAI)Change From Baseline
timeFrame: Week 12、 Week 24
measure: Clinical Disease Activity Index (CDAI)（Change From Baseline）
timeFrame: Week 12、 Week 24
measure: Change From Baseline in TJC and SJC
timeFrame: Week 24
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Week 24
measure: Change From Baseline in the Short Form 36 (SF-36) Health Survey
timeFrame: Week 24
measure: Change From Baseline in CRP
timeFrame: Week 12、Week 24
measure: Change From Baseline in ESR
timeFrame: Week 12、Week 24
measure: Change From Baseline in VAS（PtAAP-VAS、PtGADA-VAS、PhGADA-VAS）
timeFrame: Week 12、Week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: