Clinical trial NCT02467504: Low-dose Recombinant Human IL-2 for the Treatment of Rheumatoid Arthritis
Official title: A Randomized, Double Blind, Placebo-controlled Pilot-study to Evaluate Efficacy and Safety of Low-dose hrIL-2 in the Treatment of Methotrexate (MTX)-Naive Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Monash University
name: Beijing ShuangLu Pharmaceutical Co., Ltd.
First posted: 2015-06-10
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)).

Detailed description: Each RA patients (n=47) with DAS\>3.2 received low-dose IL-2+MTX+ Loxoprofen or placebo+MTX + Loxoprofen (active group: placebo group =1:1, 1 million units every other day subcutaneously (hrIL-2 1×106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3 cycles. The end points were safety and clinical and immunologic response.

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.

Primary outcomes:
measure: Percentage of Participants Achieving DAS28 Remission.
timeFrame: week 24
measure: Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria
timeFrame: week 12, week 24
measure: The Change From Baseline of Clinical Disease Activity Index (CDAI)
timeFrame: week 12, week 24
measure: The Change From Baseline of Simplified Disease Activity Index (SDAI)
timeFrame: week 12, week 24
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to week 24
measure: Percentage of CD4+ Treg Cells
timeFrame: week 12, week 24
measure: Percentage of Participants Achieving DAS28 Low Disease Activity.
timeFrame: week 12, week 24
measure: Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response
timeFrame: week 12, week 24
measure: Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria
timeFrame: week 12, week 24
measure: Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria
timeFrame: week 12, week 24
measure: Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice
timeFrame: week 12, week 24
measure: The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI)
timeFrame: week 12, week 24
measure: The Scores of SF-36 Quetionnaire
timeFrame: week 12, week 24
measure: Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]
timeFrame: week 24
measure: Erythrocyte Sedimentation Rate (ESR)
timeFrame: week 12, week 24
measure: C Reactive Protein (CRP)
timeFrame: week 12, week 24
measure: The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA)
timeFrame: week 12, week 24
measure: The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA)
timeFrame: week 12, week 24
measure: The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP)
timeFrame: week 12, week 24
measure: Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2
timeFrame: week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Rheumatology and Immunology, Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University Institute of Rheuamotology and Immunology
name: Zhanguo Li, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang X, Miao M, Zhang R, Liu X, Zhao X, Shao M, Liu T, Jin Y, Chen J, Liu H, Zhang X, Li Y, Zhou Y, Yang Y, Li R, Yao H, Liu Y, Li C, Li Y, Ren L, Su Y, Sun X, He J, Li Z. Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2022 Mar 7;7(1):67. doi: 10.1038/s41392-022-00887-2.