Low-dose Recombinant Human IL-2 for the Treatment of Rheumatoid Arthritis

NCT02467504 | Completed Phase 2 Results DMC

• 1 other identifier: hrIL-2 RA
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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)).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Achieving DAS28 Remission.

  DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6

  week 24

• Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria

  The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

  week 12, week 24

• The Change From Baseline of Clinical Disease Activity Index (CDAI)

  Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome.

  week 12, week 24

• The Change From Baseline of Simplified Disease Activity Index (SDAI)

  Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome.

  week 12, week 24

Secondary Outcomes (16)

• Number of Participants With Adverse Events

  Up to week 24

• Percentage of CD4+ Treg Cells

  week 12, week 24

• Percentage of Participants Achieving DAS28 Low Disease Activity.

  week 12, week 24

• Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response

  week 12, week 24

• Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria

  week 12, week 24

Study Arms (2)

Experimental

ACTIVE COMPARATOR

hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen

Drug: hrIL-2 active; Drug: MTX; Drug: Folic Acid; Drug: Loxoprofen

Placebo Comparator

PLACEBO COMPARATOR

hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen

Drug: hrIL-2 placebo; Drug: MTX; Drug: Folic Acid; Drug: Loxoprofen

Interventions

hrIL-2 active DRUG

hrIL-2 active (1 million U doses of hrIL-2s.c.injection)

Also known as: Human recombinant IL-2

Experimental

hrIL-2 placebo DRUG

hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection)

Also known as: placebo

Placebo Comparator

MTX DRUG

Methotrexate (oral administration)

Experimental; Placebo Comparator

Folic Acid DRUG

Folic Acid (oral administration)

Experimental; Placebo Comparator

Loxoprofen DRUG

Loxoprofen (oral administration)

Experimental; Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Monash University: collaborator
• Beijing ShuangLu Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Department of Rheumatology and Immunology, Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Related Publications (1)

• 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.

  PMID: 35250032 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Folic Acid; loxoprofen

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Prof. Zhanguo Li
• Organization: Peking university People's Hospital

13810001444@163.com

+86-13810001444

Study Officials

• Zhanguo Li, MD PhD

  Peking University Institute of Rheuamotology and Immunology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dept. Rheumatology and immunology,Peking University People's Hospital

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 10, 2015
• Study Start: July 1, 2015
• Primary Completion: January 15, 2017
• Study Completion: August 31, 2017
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-05

Locations

CN (1)