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Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus

Primary Purpose

Systemic Lupus Erythematosus

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Belimumab
Interleukin-2
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- 1. Male or female >18 years of age at screening visits 2. Patients meet the American-European Consensus Group 2002 classification criteria 3. 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.

4. Dosing of antimalarials, prednisone or equivalent, cholinergic stimulants, and topical cyclosporine required to be stable for at least 4 weeks before screening and during study; maximum doses allowed:

  • Hydroxychloroquine, 400 mg/day;
  • Prednisone, 10 mg/day

Exclusion Criteria:

  • 1. Any subject meeting any of the following criteria should be excluded: 1. Laboratory abnormality: • Hb≤9 g/dl • Neutrophil 10 mg/d) within 1 month.

    2. 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) 3. Known allergies, hyperreactivity or intolerance of tofacitinib or its excipients.

    4. Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus (EBV), tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.

    5. 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.

    6. Any known history of malignancy in the past 5 years (except for nonmelanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).

    7. 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.

    8. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.

Sites / Locations

  • Department of Rheumatology and Immunology, Peking University People's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

belimumab plus low dose IL-2

belimumab

low dose IL-2

Arm Description

10mg/kg belimumab was intravenously injected to patients with systemic lupus erythematosus every month for 24 weeks. Interleukine-2 was first added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh, then the same dose of IL-2 was injected once a week for 12 weeks subcutaneously.

10mg/kg belimumab was administrated to patients with systemic lupus erythematosus for at least 24 weeks, intravenously injected every month.

The first stage: interleukine-2 was added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh; The second stage: 1 million IU IL-2 was injected once a week for 12 weeks subcutaneously.

Outcomes

Primary Outcome Measures

Immunological responses of B cell subsets
A significant reduction of active B cell subsets including naive B cells and transitional B cells after different interventions. P values below 0.05 are considered statistically significant in this study.

Secondary Outcome Measures

Proportion of SLE Responder Index (SRI)4 response
SLE Responder Index (SRI)4 responders had ≥4-point reduction in safety of estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index(SELENA-SLEDAI) score
Prednisone dose
The improvement in prednisone dose experienced a mean corticosteroid dose reduction of ≥25% mg/day at baseline to ≤7.5 mg/day.
Immunoglobulin change from baseline
Serum samples were collected at indicated time-points for analysis of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM). Baseline is defined as the Day 0 visit from parent studies.
Autoantibody change from baseline
Blood samples were collected at indicated time-points for analysis of autoantibodies like anti-double stranded deoxyribonucleic Acid(dsDNA), antinuclear antibody (ANA). Baseline is defined as the Day 0 visit from parent studies.
Change of complement C3 and C4 Levels from baseline
Blood samples were collected at indicated time-points for analysis of complement levels like complement 3 (C3) and complement 4 (C4). Baseline is defined as the Day 0 visit from parent studies.
Safety and tolerability of the treatment
The incidence of adverse events, disease activity and clinical laboratory data throughout the study were accessed.

Full Information

First Posted
February 22, 2022
Last Updated
March 24, 2022
Sponsor
Peking University People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05262686
Brief Title
Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus
Official Title
Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus: a Randomised Prospective Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study was to explore the clinical and immunological efficacy of belimumab plus low dose IL-2 in systemic lupus erythematosus.
Detailed Description
Given that belimumab and low dose interleukin-2 (IL-2) have been widespreadly applied in the treatment of systemic lupus erythematosus (SLE), this study designed a randomised, single center, prospective study to investigate the effects and safety of combined utilization of belimumab and low dose IL-2. SLE patients were allocated in each group randomly (n=10) and regularly administered belimumab (10mg/kg) with or without IL-2 (1 million IU). Then, we evaluated the improvement of clinical and laboratory indexes and monitored the changes of immune cell subsets and cytokines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
belimumab plus low dose IL-2
Arm Type
Experimental
Arm Description
10mg/kg belimumab was intravenously injected to patients with systemic lupus erythematosus every month for 24 weeks. Interleukine-2 was first added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh, then the same dose of IL-2 was injected once a week for 12 weeks subcutaneously.
Arm Title
belimumab
Arm Type
Active Comparator
Arm Description
10mg/kg belimumab was administrated to patients with systemic lupus erythematosus for at least 24 weeks, intravenously injected every month.
Arm Title
low dose IL-2
Arm Type
Active Comparator
Arm Description
The first stage: interleukine-2 was added to the original treatment for systemic lupus erythematosus with 1 million IU qod for 12 weeks, injected subcutaneously at the outer side of upper arm, abdomen and thigh; The second stage: 1 million IU IL-2 was injected once a week for 12 weeks subcutaneously.
Intervention Type
Drug
Intervention Name(s)
Belimumab
Intervention Description
Belimumab was intravenously administrated at a dose of 10mg/kg once a month for at least 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
Recombinant Human interleukine-2
Intervention Description
Low lose interleukine-2 at a dose of 1 million IU was injected once every other day for 12 weeks, then the same dose of IL2 was injected once a week at the second stage for 12 weeks.
Primary Outcome Measure Information:
Title
Immunological responses of B cell subsets
Description
A significant reduction of active B cell subsets including naive B cells and transitional B cells after different interventions. P values below 0.05 are considered statistically significant in this study.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Proportion of SLE Responder Index (SRI)4 response
Description
SLE Responder Index (SRI)4 responders had ≥4-point reduction in safety of estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index(SELENA-SLEDAI) score
Time Frame
Week 12 and 24
Title
Prednisone dose
Description
The improvement in prednisone dose experienced a mean corticosteroid dose reduction of ≥25% mg/day at baseline to ≤7.5 mg/day.
Time Frame
Week 12 and 24
Title
Immunoglobulin change from baseline
Description
Serum samples were collected at indicated time-points for analysis of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM). Baseline is defined as the Day 0 visit from parent studies.
Time Frame
Week 12 and 24
Title
Autoantibody change from baseline
Description
Blood samples were collected at indicated time-points for analysis of autoantibodies like anti-double stranded deoxyribonucleic Acid(dsDNA), antinuclear antibody (ANA). Baseline is defined as the Day 0 visit from parent studies.
Time Frame
Week 12 and 24
Title
Change of complement C3 and C4 Levels from baseline
Description
Blood samples were collected at indicated time-points for analysis of complement levels like complement 3 (C3) and complement 4 (C4). Baseline is defined as the Day 0 visit from parent studies.
Time Frame
Week 12 and 24
Title
Safety and tolerability of the treatment
Description
The incidence of adverse events, disease activity and clinical laboratory data throughout the study were accessed.
Time Frame
Up to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - 1. Male or female >18 years of age at screening visits 2. Patients meet the American-European Consensus Group 2002 classification criteria 3. 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. 4. Dosing of antimalarials, prednisone or equivalent, cholinergic stimulants, and topical cyclosporine required to be stable for at least 4 weeks before screening and during study; maximum doses allowed: Hydroxychloroquine, 400 mg/day; Prednisone, 10 mg/day Exclusion Criteria: 1. Any subject meeting any of the following criteria should be excluded: 1. Laboratory abnormality: • Hb≤9 g/dl • Neutrophil 10 mg/d) within 1 month. 2. 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) 3. Known allergies, hyperreactivity or intolerance of tofacitinib or its excipients. 4. Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus (EBV), tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment. 5. 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. 6. Any known history of malignancy in the past 5 years (except for nonmelanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation). 7. 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. 8. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruiling Feng
Phone
+86 18952390737
Email
jsfeng001224@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jing He
Phone
+86 18611707347
Email
hejing1105@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li
Organizational Affiliation
Peking University Institute of Rheuamotology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Rheumatology and Immunology, Peking University People's Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing He, MD and PhD
Phone
+8618611707347
Email
hejing1105@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Immunological Evaluation of Belimumab Plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus

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