Low-dose Recombinant Human IL-2 for the Treatment of Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: hrIL-2 active; hrIL-2 placebo; MTX; Folic Acid; Loxoprofen
Intervention description: hrIL-2 active (1 million U doses of hrIL-2s.c.injection); hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection); Methotrexate (oral administration); Folic Acid (oral administration); Loxoprofen (oral administration)
Intervention MeSH terms: Folic Acid; Loxoprofen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, characterized by
      symmetric poly-arthritis usually involving the small joints of the hands and feet. In
      addition, various extra-joint manifestations may develop. Several immunomodulating agents
      have been attempted in the treatment of RA without achieving satisfactory results.
      Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases,
      which can be promoted by interleukin-2 (IL-2). The investigators hypothesized that low-dose
      IL-2 could be a novel therapy in active RA patients. This clinical study will test the
      efficacy and safety of low dose IL-2 treatment in RA. The investigators perform a
      single-centre, double-blind pilot trial with hrIL-2 in RA. The investigators evaluate the
      effectiveness and safeness of low-dose hrIL-2 for RA by randomized controlled study (hrIL-2
      (N = 23) + Methotrexate (MTX)+ Loxoprofen versus placebo+MTX + Loxoprofen group (N = 24)).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female ≥18 and ≤70 years of age at time of screening

          -  Diagnosed with rheumatoid arthritis

          -  Must have active disease with DMARDs (Disease Modifying Anti-Rheumatic Drugs) except
             MTX, the doses had been stable for at least 3 months before baseline

          -  Moderate or severe rheumatoid arthritis during screening, as defined by a disease
             activity score (28 joint) calculated using the C-reactive protein formula (DAS28-ESR)
             > 3.2

          -  Have given written informed consent

        Exclusion Criteria:

          -  Patient presenting or having a history of other inflammatory joint disease

          -  Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis
             or erythema multiforme

          -  Patient with significantly impaired bone marrow function or significant anaemia,
             leucopenia or thrombocytopenia due to causes or other than active rheumatoid arthritis

          -  Persistent infection or severe infection within 3 months before enrollment,

          -  Uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease,
             active inflammatory bowel disease, active peptic ulcer disease, terminal illness or
             other medical condition which, in the opinion of the investigator, would put the
             patient at risk to participate in the study,

          -  Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major
             systemic disease making implementation of the protocol or interpretation of the study
             results difficult

          -  Severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome)
             with serum albumin < 30 g/L

          -  Moderate or severe impairment of renal function, as known by serum creatinine >
             133μmol/L (or 1.5 mg/dl)

          -  Patient with history of recent and clinically significant drug or alcohol abuse

          -  Impairment of liver function or persisting ALT (SGPT) elevations of more than 2-fold
             the upper limit of normal

          -  Known HIV positive status

          -  Known positive serology for hepatitis B or C

          -  Patient with hypersensitivity to any of the excipients in the tablets of methotrexate

          -  Pregnancy

          -  Breastfeeding

          -  Women of childbearing potential, except if they fulfill specific conditions,

          -  Men wishing to father children during the course of the study or within the 24 months
             thereafter (or 3 month with the washout procedure)

          -  Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or
             lymphoproliferative disease, or any patient who has received total lymphoid
             irradiation.

          -  Enrollment in any other clinical trial involving off-label use of an investigational
             drug or device, or enrollment in any other type of medical research

          -  Any active infection (including chronic or localized infections) for which
             anti-infectives were indicated within 28 days prior to first investigational product
             dose

          -  BMI(body mass index) under 18.5 kg/m2 or more than 30 kg/m2

          -  The above information is not intended to contain all considerations relevant to a
             patient's potential participation in a clinical trial.