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Efficacy of Interleukin-2 Gargle in the Treatment of Oral Mucosa Lesion in Pemphigus Vulgaris

Primary Purpose

Pemphigus Vulgaris

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
recombinant human interleukin-2 (rhIL-2)
placebo
Sponsored by
Second Xiangya Hospital of Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pemphigus Vulgaris focused on measuring pemphigus vulgaris, oral mucosal lesion, interleukin-2

Eligibility Criteria

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

Inclusion Criteria:

  1. Age: between 18 years and 70 years;
  2. Patients definitely diagnosed with pemphigus vulgaris according to 'Diagnostic Criteria for Pemphigus Vulgaris (Autoimmune Disease Sub-Professional Committee of Dermatologist Branch of Chinese Medical Doctor Association)'; or pemphigus vulgaris has been diagnosed in the past.
  3. Visible oral mucosa lesion due to pemphigus;
  4. Mucosal-dominant PV or moderate mucocutaneous PV (PDAI score: 15-45);
  5. Written informed consent was obtained, volunteer to participate in the project and complete as required.

Exclusion Criteria:

  1. Patients with severe diseases of heart, brain, lungs, liver, kidney or blood system; patients experienced organ transplantation;
  2. Patients with any acute severe infection such as pyemia and cellulitis, active tuberculosis, or an infection history of human immunodeficiency virus (HIV);
  3. Patients with allergic skin diseases with obvious pruritus such as eczema or urticaria, blood routine examination show elevated eosinophils or have a clear history of allergy to rhIL-2;
  4. Patients with persistent ventricular tachycardia, uncontrolled arrhythmias, chest pain with ECG changes, angina or myocardial infarction, cardiac tamponade;
  5. Patients with nausea, vomiting, peptic ulcer or intestinal ischemia;
  6. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment;
  7. Pregnant women, lactating women or women who are ready to conceive within 3 months;
  8. Patients receiving treatment of immunosuppressants in the last 3 months;
  9. Patients receiving continuous treatment of glucocorticoids with a dose of more than 0.75 mg/kg/d in the last 2 weeks;
  10. Patients with oral fungal infection but don't receive antifungal therapy;
  11. Participated in other clinical trials within 3 months before the screening.

Sites / Locations

  • The Second Xiangya Hospital of Central South UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

experimental group

control group

Arm Description

Patients will receive rhIL-2 solution oral gargle twice per day (2 million units of rhIL-2 dissolved in 5ml normal saline for each dose, garble for 3 minutes) and continue for 3 weeks. A standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, moderate mucocutaneous PV: prednisone 0.75 mg/kg/d) will be applied at the same time.

Patients will receive placebo solution oral gargle twice per day (5ml for each dose, garble for 3 minutes) and continue for 3 weeks. A standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, moderate mucocutaneous PV: prednisone 0.75 mg/kg/d) will be applied at the same time.

Outcomes

Primary Outcome Measures

The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 21-day treatment.
(PDAI score on Day 0 - PDAI score on Day 21)/PDAI score on Day 0 × 100%

Secondary Outcome Measures

The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 7-, 14-, 28- and 42-day treatment, respectively.
(PDAI score on Day 0 - PDAI score on Day N)/PDAI score on Day 0 × 100%
The decline of Oral Disease Severity Score (ODSS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
(ODSS on Day 0 - ODSS on Day N)/ODSS on Day 0 × 100%
The decline of oral mucosa Visual Analogue Scale(VAS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
(VAS on Day 0 - VAS on Day N)/VAS on Day 0 × 100%
The decline of Physician's Global Assessment (PGA) score for oral mucosa damage after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
(PGA score on Day 0 - PGA score on Day N)/PGA score on Day 0 × 100%
The decline of sera autoantibodies titer after a 21- and 42-day treatment, respectively.
The autoantibodies including anti-Dsg3 and anti-Dsg1 antibodies titer are detected by ELISA
The dose of glucocorticoids on Day 28 and Day 42, respectively.
prednisone (mg/d)
The percentage of patients receiving incremental dose of glucocorticoids, steroid pulse therapy, or combined with immunosuppressants/intravenous immunoglobulin(IVIG)/biological agents on Day 28 and Day 42, respectively.
The percentage of patients from whose oral mucosa the fungal infection can be detected on Day 21 and Day 42.
The change of white blood cell (WBC) counts on Day 21 and Day 42.
The unit of WBC: 10^9/L
The change of serum potassium level on Day 21 and Day 42.
The unit of serum potassium level: mmol/L
The change of fasting blood-glucose (FBS) level on Day 21 and Day 42.
The unit of FBS level: mmol/L
The change of serum albumin level on Day 21 and Day 42.
The unit of serum albumin level: g/L
The safety evaluation about the drug adverse reactions throughout the entire study process.
the adverse reactions of rhIL-2 include fever, shiver, muscular soreness, nausea, emesis, rash, capillary leak syndrome.

Full Information

First Posted
July 3, 2019
Last Updated
January 31, 2021
Sponsor
Second Xiangya Hospital of Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT04023149
Brief Title
Efficacy of Interleukin-2 Gargle in the Treatment of Oral Mucosa Lesion in Pemphigus Vulgaris
Official Title
Short-term Efficacy of Interleukin-2 Gargle Combined With Systemic Use of Glucocorticoids in the Treatment of Oral Mucosal Lesion in Pemphigus Vulgaris: a Randomized, Controlled, Double-blind, Multicenter Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 2, 2020 (Actual)
Primary Completion Date
June 1, 2021 (Anticipated)
Study Completion Date
December 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Xiangya Hospital of Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This clinical study will test the short-term efficacy of interleukin-2 gargle combined with systemic use of glucocorticoids in the treatment of oral mucosal lesions in mucosal-dominant pemphigus vulgaris and moderate mucocutaneous pemphigus vulgaris.
Detailed Description
Backgrounds: Pemphigus vulgaris (PV) is a life-threatening autoimmune bullous skin disease characterized by blisters or bullae on the skin and mucosal membranes. The formation of painful erosion surface after rupture of blisters may result in infection, haemorrhage and even electrolyte imbalance due to excessive water loss. PV can be divided into two types: mucocutaneous PV and mucosal-dominant PV. Patients with mucocutaneous PV not only suffer from severe mucosal damage but also general skin lesions, while slight or no skin lesions involved in patients with mucosal-dominant PV. Oral mucosal damage occurred 3 months to 1 year before skin lesions in about 60% of PV patients. The most common involving parts of the oral mucosa are pars buccalis and oropharynx, presenting with persistent and painful erosion or ulceration, which leads to difficulty in feeding and aggravates the electrolyte imbalance. Glucocorticoid is the main treatment strategy of PV. Besides the blisters and erosion, complications of long-term use of glucocorticoid are also the death causes of PV patients, such as osteoporosis, hyperglycemia, hypertension, hypokalemia, femoral head necrosis, peptic ulcer, and infection. Many patients have gotten remission from the standard application of glucocorticoids, Immunosuppressants and biological agent. However, there is still a part of patients that are insensitive to these drugs or intolerant the side effects of corticosteroids. Even for those steroid-sensitive patients, the healing of oral mucosa often takes a long course, lasting from weeks to months, which has a serious impact on the quality of life. It is a critical problem to develop novel therapeutics to accelerate the healing of oral mucosa. Recombinant human interleukin-2 (rhIL-2) is an immunomodulator agent commonly used in the treatment of patients with tumours. The safety and efficacy of low dose rhIL-2 have been demonstrated in the treatment of type I diabetes, systemic lupus erythematosus, and graft-versus-host disease. We found that topical application of rhIL-2 can effectively relieve pain and improve the condition of oral mucosa for PV patients. Studies have shown that IL-2 selectively modulates CD4+ T cell subsets and increases the amounts and function of regulatory T cells. Moreover, IL-2 plays an important role in the proliferation of fibroblasts and wound healing. These evidences provide us the theoretical basis to explore the potential mechanism of rhIL-2 in treatment of mucosal damage of patients with PV. Design of Study: This is a randomized, controlled, double-blind, multicenter clinical trial to assess the safety and short-term efficacy of rhIL-2 for oral erosion in patients with pemphigus. Methods: rhIL-2 oral gargle combined with the standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, mucocutaneous PV: prednisone 1 mg/kg/d) will be applied to pemphigus patients meeting the inclusion criteria. The end points include clinical response and immunological changes, as well as safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pemphigus Vulgaris
Keywords
pemphigus vulgaris, oral mucosal lesion, interleukin-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
experimental group
Arm Type
Experimental
Arm Description
Patients will receive rhIL-2 solution oral gargle twice per day (2 million units of rhIL-2 dissolved in 5ml normal saline for each dose, garble for 3 minutes) and continue for 3 weeks. A standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, moderate mucocutaneous PV: prednisone 0.75 mg/kg/d) will be applied at the same time.
Arm Title
control group
Arm Type
Placebo Comparator
Arm Description
Patients will receive placebo solution oral gargle twice per day (5ml for each dose, garble for 3 minutes) and continue for 3 weeks. A standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, moderate mucocutaneous PV: prednisone 0.75 mg/kg/d) will be applied at the same time.
Intervention Type
Drug
Intervention Name(s)
recombinant human interleukin-2 (rhIL-2)
Intervention Description
Drug: rhIL-2; Pharmaceutical form: solution; Route of administration: oral gargle.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Drug: placebo; Pharmaceutical form: solution; Route of administration: oral gargle.
Primary Outcome Measure Information:
Title
The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 21-day treatment.
Description
(PDAI score on Day 0 - PDAI score on Day 21)/PDAI score on Day 0 × 100%
Time Frame
from baseline to 21 days treatment
Secondary Outcome Measure Information:
Title
The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 7-, 14-, 28- and 42-day treatment, respectively.
Description
(PDAI score on Day 0 - PDAI score on Day N)/PDAI score on Day 0 × 100%
Time Frame
from baseline to 7, 14, 28 and 42 days, respectively
Title
The decline of Oral Disease Severity Score (ODSS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
Description
(ODSS on Day 0 - ODSS on Day N)/ODSS on Day 0 × 100%
Time Frame
from baseline to 7, 14, 21, 28 and 42 days, respectively
Title
The decline of oral mucosa Visual Analogue Scale(VAS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
Description
(VAS on Day 0 - VAS on Day N)/VAS on Day 0 × 100%
Time Frame
from baseline to 7, 14, 21, 28 and 42 days, respectively
Title
The decline of Physician's Global Assessment (PGA) score for oral mucosa damage after a 7-, 14-, 21-, 28- and 42-day treatment, respectively.
Description
(PGA score on Day 0 - PGA score on Day N)/PGA score on Day 0 × 100%
Time Frame
from baseline to 7, 14, 21, 28 and 42 days, respectively
Title
The decline of sera autoantibodies titer after a 21- and 42-day treatment, respectively.
Description
The autoantibodies including anti-Dsg3 and anti-Dsg1 antibodies titer are detected by ELISA
Time Frame
from baseline to 21 and 42 days, respectively
Title
The dose of glucocorticoids on Day 28 and Day 42, respectively.
Description
prednisone (mg/d)
Time Frame
28 and 42 days
Title
The percentage of patients receiving incremental dose of glucocorticoids, steroid pulse therapy, or combined with immunosuppressants/intravenous immunoglobulin(IVIG)/biological agents on Day 28 and Day 42, respectively.
Time Frame
28 and 42 days
Title
The percentage of patients from whose oral mucosa the fungal infection can be detected on Day 21 and Day 42.
Time Frame
21 and 42 days
Title
The change of white blood cell (WBC) counts on Day 21 and Day 42.
Description
The unit of WBC: 10^9/L
Time Frame
21 and 42 days
Title
The change of serum potassium level on Day 21 and Day 42.
Description
The unit of serum potassium level: mmol/L
Time Frame
21 and 42 days
Title
The change of fasting blood-glucose (FBS) level on Day 21 and Day 42.
Description
The unit of FBS level: mmol/L
Time Frame
21 and 42 days
Title
The change of serum albumin level on Day 21 and Day 42.
Description
The unit of serum albumin level: g/L
Time Frame
21 and 42 days
Title
The safety evaluation about the drug adverse reactions throughout the entire study process.
Description
the adverse reactions of rhIL-2 include fever, shiver, muscular soreness, nausea, emesis, rash, capillary leak syndrome.
Time Frame
through study completion, an average of 42 days

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: Age: between 18 years and 70 years; Patients definitely diagnosed with pemphigus vulgaris according to 'Diagnostic Criteria for Pemphigus Vulgaris (Autoimmune Disease Sub-Professional Committee of Dermatologist Branch of Chinese Medical Doctor Association)'; or pemphigus vulgaris has been diagnosed in the past. Visible oral mucosa lesion due to pemphigus; Mucosal-dominant PV or moderate mucocutaneous PV (PDAI score: 15-45); Written informed consent was obtained, volunteer to participate in the project and complete as required. Exclusion Criteria: Patients with severe diseases of heart, brain, lungs, liver, kidney or blood system; patients experienced organ transplantation; Patients with any acute severe infection such as pyemia and cellulitis, active tuberculosis, or an infection history of human immunodeficiency virus (HIV); Patients with allergic skin diseases with obvious pruritus such as eczema or urticaria, blood routine examination show elevated eosinophils or have a clear history of allergy to rhIL-2; Patients with persistent ventricular tachycardia, uncontrolled arrhythmias, chest pain with ECG changes, angina or myocardial infarction, cardiac tamponade; Patients with nausea, vomiting, peptic ulcer or intestinal ischemia; Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment; Pregnant women, lactating women or women who are ready to conceive within 3 months; Patients receiving treatment of immunosuppressants in the last 3 months; Patients receiving continuous treatment of glucocorticoids with a dose of more than 0.75 mg/kg/d in the last 2 weeks; Patients with oral fungal infection but don't receive antifungal therapy; Participated in other clinical trials within 3 months before the screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qianjin Lu, MD, PhD
Phone
+86-13787097676
Email
qianlu5860@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hai Long
Phone
+86-18229743206
Email
longhai021123@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qianjin Lu
Organizational Affiliation
Central South University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiangqi Tang, MD, PhD
Phone
+86-731-84896038
Email
xiangyagcp@126.com
First Name & Middle Initial & Last Name & Degree
Qianjin Lu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hai Long, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy of Interleukin-2 Gargle in the Treatment of Oral Mucosa Lesion in Pemphigus Vulgaris

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