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

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ClinicalTrials.gov Identifier: NCT04023149
Recruitment Status : Not yet recruiting
First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Qianjin Lu, MD, PhD, Second Xiangya Hospital of Central South University

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.

Condition or disease Intervention/treatment Phase
Pemphigus Vulgaris Drug: recombinant human interleukin-2 (rhIL-2) Drug: placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 10, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus Steroids

Arm Intervention/treatment
Experimental: experimental group
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 1 mg/kg/d) will be applied at the same time.
Drug: recombinant human interleukin-2 (rhIL-2)
Drug: rhIL-2; Pharmaceutical form: solution; Route of administration: oral gargle.

Placebo Comparator: control group
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 1 mg/kg/d) will be applied at the same time.
Drug: placebo
Drug: placebo; Pharmaceutical form: solution; Route of administration: oral gargle.




Primary Outcome Measures :
  1. The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 21-day treatment. [ Time Frame: from baseline to 21 days treatment ]
    (PDAI score on Day 0 — PDAI score on Day 21)/PDAI score on Day 0 × 100%


Secondary Outcome Measures :
  1. The decline of the oral mucosa score of Pemphigus Disease Area Index (PDAI) after a 7-, 14-, 28- and 42-day treatment, respectively. [ Time Frame: from baseline to 7, 14, 28 and 42 days, respectively ]
    (PDAI score on Day 0 — PDAI score on Day N)/PDAI score on Day 0 × 100%

  2. The decline of Oral Disease Severity Score (ODSS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively. [ Time Frame: from baseline to 7, 14, 21, 28 and 42 days, respectively ]
    (ODSS on Day 0 — ODSS on Day N)/ODSS on Day 0 × 100%

  3. The decline of oral mucosa Visual Analogue Scale(VAS) after a 7-, 14-, 21-, 28- and 42-day treatment, respectively. [ Time Frame: from baseline to 7, 14, 21, 28 and 42 days, respectively ]
    (VAS on Day 0 — VAS on Day N)/VAS on Day 0 × 100%

  4. The decline of Physician's Global Assessment (PGA) score for oral mucosa damage after a 7-, 14-, 21-, 28- and 42-day treatment, respectively. [ Time Frame: from baseline to 7, 14, 21, 28 and 42 days, respectively ]
    (PGA score on Day 0 — PGA score on Day N)/PGA score on Day 0 × 100%

  5. The decline of sera autoantibodies titer after a 21- and 42-day treatment, respectively. [ Time Frame: from baseline to 21 and 42 days, respectively ]
    The autoantibodies including anti-Dsg3 and anti-Dsg1 antibodies titer are detected by ELISA

  6. The decline of salivary autoantibodies titer after a 21- and 42-day treatment, respectively. [ Time Frame: from baseline to 21 and 42 days, respectively ]
    The autoantibodies including anti-Dsg3 and anti-Dsg1 antibodies titer are detected by ELISA

  7. The dose of glucocorticoids on Day 28 and Day 42, respectively. [ Time Frame: 28 and 42 days ]
    prednisone (mg/d)

  8. 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 ]
  9. The percentage of patients from whose oral mucosa the fungal infection can be detected on Day 7, Day 14, Day 21, Day 28 and Day 42. [ Time Frame: 7, 14, 21, 28 and 42 days, respectively ]
  10. The change of white blood cell (WBC) counts on Day 21 and Day 42. [ Time Frame: 21 and 42 days ]
    The unit of WBC: 10^9/L

  11. The change of serum potassium level on Day 21 and Day 42. [ Time Frame: 21 and 42 days ]
    The unit of serum potassium level: mmol/L

  12. The change of fasting blood-glucose (FBS) level on Day 21 and Day 42. [ Time Frame: 21 and 42 days ]
    The unit of FBS level: mmol/L

  13. The change of serum albumin level on Day 21 and Day 42. [ Time Frame: 21 and 42 days ]
    The unit of serum albumin level: g/L

  14. The safety evaluation about the drug adverse reactions throughout the entire study process. [ Time Frame: through study completion, an average of 42 days ]
    the adverse reactions of rhIL-2 include fever, shiver, muscular soreness, nausea, emesis, rash, capillary leak syndrome.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: between 18 years and 60 years;
  2. Patients definitely diagnosed with pemphigus vulgaris based on a comprehensive evaluation of the clinical materials, anti-Dsg3 and anti-Dsg1 autoantibodies detection, skin biopsy and direct immunofluorescence(DIF); patients definitely diagnosed with mucosal-dominant PV based on a comprehensive evaluation of the clinical materials, anti-Dsg3 and anti-Dsg1 autoantibodies detection.
  3. Visible oral mucosa lesion due to pemphigus;
  4. Mucosal-dominant PV or moderate mucocutaneous PV (PDAI score: 9-24);
  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, or an infection history of hepatitis B or C virus, Mycobacterium tuberculosis, or 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 or lactating women;
  8. Patients receiving treatment of immunosuppressants in the last 3 months;
  9. Patients receiving continuous treatment of glucocorticoids with a dose of more than 1 mg/kg/d in the last 2 weeks;
  10. Patients with oral fungal infection but don't receive antifungal therapy;
  11. Participants in other clinical trials.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04023149


Contacts
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Contact: Qianjin Lu, MD, PhD +86-13787097676 qianlu5860@gmail.com
Contact: Hai Long +86-18229743206 longhai021123@163.com

Locations
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China, Hunan
The Second Xiangya Hospital of Central South University Not yet recruiting
Changsha, Hunan, China, 410011
Contact: Xiangqi Tang, MD, PhD    +86-731-84896038    xiangyagcp@126.com   
Principal Investigator: Qianjin Lu, MD, PhD         
Sub-Investigator: Hai Long, MD, PhD         
Sponsors and Collaborators
Second Xiangya Hospital of Central South University
Investigators
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Principal Investigator: Qianjin Lu Central South University

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Responsible Party: Qianjin Lu, MD, PhD, Professor and Director, Dept. of Dermatology, The Second Xiangya Hospital of Central South University, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT04023149     History of Changes
Other Study ID Numbers: IPOEMS201903
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Qianjin Lu, MD, PhD, Second Xiangya Hospital of Central South University:
pemphigus vulgaris
oral mucosal lesion
interleukin-2

Additional relevant MeSH terms:
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Pemphigus
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Aldesleukin
Interleukin-2
Pharmaceutical Solutions
Glucocorticoids
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents