Clinical trial NCT04062006: Low-dose Interleukin-2 Treatment on Polymyalgia Rheumatica
Official title: Low-dose Interleukin-2 Treatment on Polymyalgia Rheumatica
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Polymyalgia Rheumatica
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2019-08-20
Enrollment: 15
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to explore the clinical and immunological efficacy of low-dose Interleukin-2 (IL-2) on polymyalgia rheumatica.

Detailed description: The investigators designed a single center, open-label, prospective study that routinely administered low-dose IL-2 therapy to monitor the improvement of clinical and laboratory parameters to explore its efficacy and to observe changes in immune cell subsets and cytokines. One million units of Recombinant Human Interleukin-2 (rhIL-2) was administered subcutaneously five days every week for 4 weeks and then once a week for 8 weeks. All patients were followed up for 3 months after treatment.

Eligibility criteria: Inclusion Criteria:

1. Male or female, aged ≥50 years at screening visits
2. Diagnostics meet the 1986 Nancy recommendations
3. Apply glucocorticoids (≤10 mg/d prednisone or equivalent doses of other hormones), DMARDs (eg methotrexate, hydroxychloroquine, azathioprine, morphine, Ester, leflunomide, cyclosporine, etc.) must be stable for 4 weeks and do not increase hormone doses or other immunosuppressive agents throughout the study. If the enrolled doctor plans to stop using the current immunosuppressant or glucocorticoid, the elution period needs to be followed before enrollment. Each drug needs to meet the following elution period

   * Glucocorticoid-2 weeks
   * Immunosuppressants (including methotrexate, azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) - 4 weeks
   * Intravenous immunogloblin (IVIg) or cyclophosphamide - 2 months
   * Rituximab - 6 months
   * Other biological agents (infliximab, adalimumab, etanercept, anakinra, etc.) -12 weeks
4. The patient must be informed in writing of the consent to participate in the trial and the patient is expected to be able to comply with the requirements of the study follow-up plan and other protocols.
5. Excluding Horton syndrome
6. The amount of non-steroidal dose was stable 4 weeks before enrollment

Exclusion Criteria:

Any subject meeting any of the following criteria should be excluded:

1. Use rituximab or other monoclonal antibodies within 6 months.
2. Received high doses of glucocorticoid (\>10 mg/d) within 1 month.
3. Serious complications: including heart failure (≥ New York Heart Association (NYHA) class III), renal insufficiency (creatinine clearance ≤ 30 ml/min), liver dysfunction (serum Alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of normal, or total bilirubin greater than Normal upper limit)
4. Other serious, progressive or uncontrollable hematology, gastrointestinal, endocrine, pulmonary, cardiac, neurological or brain disorders (including demyelinating diseases such as multiple sclerosis).
5. Known allergies, hyperreactivity or intolerance of IL-2 or its excipients.
6. Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, EB virus, tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.
7. Chest imaging showed abnormalities in malignant tumors or current active infections (including tuberculosis) within 3 months prior to the first use of the study drug.
8. Infection with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, it is recommended to consult a doctor who has expertise in treating HIV or hepatitis C virus infection.
9. Any known history of malignancy in the past 5 years (except for non-melanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).
10. Uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past 3 years, may hinder the successful completion of the study.
11. Accept or expect to receive any live virus or bacterial vaccination within 3 months prior to the first injection of the study agent, during the study period, or within 4 months after the last injection of the study agent. Bacillus Calmette-Guerin (BCG) vaccine was inoculated within 12 months after screening.
12. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.
13. Men whose partners have fertility potential but are reluctant to use appropriate medically-accepted contraceptives during treatment and 12 months after the study.

Primary outcomes:
measure: Foxp3+Treg cells: change in percentage of total lymphocytes
timeFrame: week 12
Secondary outcomes:
measure: Physician's Global Disease Activity VAS
timeFrame: week12 and 24
measure: Patient's Global Disease Activity VAS
timeFrame: week12 and 24
measure: Safety and tolerability of interleukin-2 as assessed by incidence of adverse events reported and observed
timeFrame: up to 24 weeks
measure: Patient reported outcome 36-item Short Form Health Survey (SF-36)
timeFrame: wee12 and 24
measure: Proportion of patients with Low disease activity (PMR-AS<10) with steroid independence (GCs ≤5 mg absolute value) or decrease ≥ 10 mg
timeFrame: from week 0 to week 12 and 24
measure: Cumulative dosages of glucocorticoids (GCs)
timeFrame: week 12 and 24
measure: The proportion of patients with PMR-activity score (AS) < 1.5; 10; 17
timeFrame: week 12 and 24
Other outcomes:
Locations:
Study officials:
References:
citation: Kermani TA, Warrington KJ. Advances and challenges in the diagnosis and treatment of polymyalgia rheumatica. Ther Adv Musculoskelet Dis. 2014 Feb;6(1):8-19. doi: 10.1177/1759720X13512450.
citation: Brooks RC, McGee SR. Diagnostic dilemmas in polymyalgia rheumatica. Arch Intern Med. 1997 Jan 27;157(2):162-8.
citation: Bird HA, Esselinckx W, Dixon AS, Mowat AG, Wood PH. An evaluation of criteria for polymyalgia rheumatica. Ann Rheum Dis. 1979 Oct;38(5):434-9. doi: 10.1136/ard.38.5.434.