A Study of the Efficacy and Safety of TACI-antibody Fusion Protein Injection (RC18) in Subjects With Inadequate Response to MTX Due to Treat Moderate and Severe Rheumatoid Arthritis.

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2023
• Main ID: NCT03016013
• Date of registration: 08/01/2017
• Prospective Registration: Yes
• Primary sponsor: RemeGen Co., Ltd.
• Public title: A Study of the Efficacy and Safety of TACI-antibody Fusion Protein Injection (RC18) in Subjects With Inadequate Response to MTX Due to Treat Moderate and Severe Rheumatoid Arthritis.
• Scientific title: A Phase III Study of RC18,a Recombinant Human B Lymphocyte Stimulating Factor Receptor-Antibody Fusion Protein in Subjects With Poor Efficacy of MTX Due to Treat Moderate and Severe Rheumatoid Arthritis.
• Date of first enrolment: April 5, 2017
• Target sample size: 480
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03016013
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

China

Contacts

• Name: Fengchun Zhang
• Affiliation: Peking Union Medical College Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of adult onset RA by a physician as defined by the 1987 and/or 2010 ACR
criteria and ESR or C - reaction protein ( CRP ) is greater than the normal range;

- Aged 18-65 years old;

- Consent to use effective contraception during the study period (women of childbearing
age);

- Patients with an inadequate response to existing therapies at least one anti-TNFs
Infliximab (Remicade ) at least three times, adalimumab (Humira), at least four times,
etanercept ( Enbrel) use at least 8 weeks, etanercept use at least 8 weeks.And Last
medication time to randomization more than 12 weeks;

- Voluntarily signed informed consent;

- Patients have been taking MTX for at least 12 weeks at the screening and maintaining
dose stability =7.5mg/ weeks (or equivalent dose) 4 weeks before randomization;

- Treatment with traditional oral disease-modifying antirheumatic drugs (DMARD)
/immunosuppressive agents other than MTX within 4 weeks or 12 weeks before the
screening visit, depending on DMARD;

- If subjects are receiving treatment of corticosteroid, must stabilize dose (dose of
prednisone) at least equal to or less than 10mg/day for 4 weeks (before
randomization);

- If subjects are receiving treatment of NSAIDs,must stabilize dose (dose of prednisone)
at least 4 weeks (before randomization);

- When the patient's condition to achieve moderate to severe active RA at the screening,
defined as at least 6/68 tenderness joints and at least 6/66 swollen joints.

Exclusion Criteria:

- Exclusion criteria associated with rheumatoid disease:

1. The subjects with any other inflammatory arthritis (such as juvenile chronic
arthritis, regional enteritis (Krohn S disease), ulcerative colitis, gout, active
vasculitis, psoriatic arthritis or ankylosing spondylitis);

2. The subjects with secondary, non inflammatory arthritis (such as osteoarthritis
or fibromyalgia), and researchers think the symptoms of arthritis can interfere
with judgment and evaluation study on therapeutic effects of drugs.But secondary
Sjogren syndrome (SjÖgren), thyroiditis without exclusion;

3. The subjects had a history of prosthetic joint infection, whenever the infection
occurred, and the artificial joint is still in the body;

4. The subjects due to RA and/or shoulder hand syndrome IV grade received more than
3 times the arthroplasty;

5. The subjects' Types of X-ray phases reach IV phase.

- The subjects can not accept the prohibited drugs listed in the following table:

1. Use of analgesics (acetaminophen / paracetamol) within 24 hours before baseline
assessment;

2. dosage regimen of nonsteroidal anti-inflammatory analgesic NSAIDs/COX-2
inhibitors (except acetaminophen) have occurred any change within 14 days before
baseline assessment;

3. The dosage of oral glucocorticoids have occurred any change within 28 days before
baseline assessment;

4. Intramuscular injection/intravenous injection/intra-articular injection of
glucocorticoid has used within 28 days before baseline assessment;

5. Intra-articular injection of hyaluronic acid has used within 28 days before
baseline assessment;

6. Tripterygium wilfordii or other traditional Chinese medicine for treating RA has
used within 28 days before baseline assessment.

- The researchers confirmed that the subjects had current or recent severe, progressive
and or not controlled heart, lung, liver, kidney and other important organs and blood,
endocrine system lesions and history; Abnormal laboratory parameters need to be
excluded, including but not limited to:

1. Cr >135µmol/L or 5 times the upper limit of laboratory reference value;

2. WBCs<3x 109/L;

3. neutrophile granulocyte <1.5×109/L;

4. hemoglobin<85g/L;

5. platelet count<80x 109/L;

6. total bilirubin > 1.5 times the upper limit of laboratory reference value;

7. AST > 2 times the upper limit of laboratory reference value;

8. ALT > 2 times the upper limit of laboratory reference value;

9. alkaline phosphatase > 2 times the upper limit of laboratory reference value.

- HBsAg-surface antigen positive patients are not allowed to be selected, but only anti
HBC single positive is added to do HBV-DNA quantitative detection, if the HBV-DNA
quantity is negative can not be regarded as the exclusion.

- The anti-HCV of patients show positive.

- Infection with herpes zoster or HIV virus at the screening.

- The subjects at high risk of infection ;such as leg ulcers, indwelling catheter,
persistent or recurrent chest infection, completely bedridden or sedentary wheelchair
subjects.

- There is a history of chronic infection, severe or life-threatening infections
(including shingles) within the last 6 months, or any signs or symptoms during the
screening period that may indicate an infection (e.g. fever, cough).

- the subjects currently or recently (30 days before screening) suffers from severe
viral, bacterial, fungal, or parasitic infections.

- pregnant, lactating women and men or women who have birth plans in the past 6 months.

- Have a history of allergic reaction to contrast agent for parenteral administration
and human biological medicines.

- The subjects receive live vaccine/attenuated vaccine within the first 8 weeks before
screening or those who are known to receive live vaccine/attenuated vaccine during the
trial.

- Have participated in any clinical trial in the first 28 days of the initial screening
or 5 times half-life period of the study compound (taking the time for the elderly).

- Patients with using of biological agents for the treatment of DMARDs within three
months.

- Active TB at screening.Exception for patients with PPD=15mm.But Patients with anti
tuberculosis treatment for 3 years without relapse are allowed to participate in the
trial.

- Malignant tumor patients :the patients who suffering from malignant tumor has been
removed and no recurrence or who with cervical carcinoma in situ have evidence of
metastatic disease and with basal cell or squamous cell carcinoma had been completely
removed and at least 3 years without recurrence can participate in.

- The patients with a history of lymphoproliferative disease (including ly


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Moderate and Severe RheumatoId Arthritis

Intervention(s)

Biological: Placebo plus MTX

Biological: RC18 160 mg plus MTX

Primary Outcome(s)

The proportion of patients in each group reached ACR20 at week 24 [Time Frame: Week 24(Visit 9)]

Secondary Outcome(s)

Percentage of Participants With American College of Rheumatology 20% ,50% and 70% (ACR20, ACR50 and ACR70) Response [Time Frame: Week 4, Week 8, Week 12, Week 28, Week 32, Week 40, Week48]

Change From Baseline in Joint Space Narrowing and Erosions at week 24 and week 48. [Time Frame: Week 24,Week48]

Percentage of Participants Achieving American College of Rheumatology ACR50 and ACR70 Responses at week 12 or week 24. [Time Frame: Week 12 and Week 24]

Percentage of Participants Achieving Low Disease Activity and clinical remission. (DAS28 =3.20 and DAS28 < 2.6). [Time Frame: Week 24]

Sharp Score Relative Change from Baseline at Week 24 [Time Frame: Week 24]

Percentage of Participants Achieving American College of Rheumatology ACR50 and ACR70 Responses at week 24. [Time Frame: Week 24]

Secondary ID(s)

C008 RACLLI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors