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Immunoregulatory Therapy for 2019-nCoV

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ClinicalTrials.gov Identifier: NCT04268537
Recruitment Status : Not yet recruiting
First Posted : February 13, 2020
Last Update Posted : February 13, 2020
Sponsor:
Information provided by (Responsible Party):
Jianfeng Xie, Southeast University, China

Brief Summary:
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in 2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which 11 million patients died. Studies in China also showed that more than 1 million patients died of sepsis in 2015. Previous studies have suggested that sepsis are often secondary to excessive inflammatory response syndrome. However, treatment measures targeting excessive inflammatory response failed to effectively improve the prognosis of patients. PD-1 and PD-L1 are key mediators in T cell depletion in sepsis patients. Therefore, the investigators try to performe a clinical research to investigate the efficacy of PD-1 and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.

Condition or disease Intervention/treatment Phase
2019 nCoV, PD-1 Drug: PD-1 blocking antibody+standard treatment Drug: Thymosin+standard treatment Other: standard treatment Phase 2

Detailed Description:

Sepsis, including viral infections, are major causes of death worldwide. Studies show that in 2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which eleven million patients died. Studies in China also showed that more than one million patients died of sepsis in 2015. Therefore, how to effectively reduce the mortality of patients with sepsis has become a focus of clinical and basic research.

Previous studies have suggested that sepsis are often secondary to excessive inflammatory response syndrome. However, treatment measures targeting excessive inflammatory response failed to effectively improve the prognosis of patients. The reason is that sepsis-related immune dysfunction can increase the risk of secondary infection and even affect the fatality rate.

The immune checkpoint pathway is the endogenous component of the immune system, which is responsible for checking the immune response and keeping it in a normal physiological state. Tumor cells can evade host recognition through this pathway. One of these immunocheckpoint pathways is the PD-1 and PD-L1 pathways. PD-1 is a receptor expressed on the surface of T cells and ACTS as a negative regulator of T cell function. Monoclonal antibody blocking the activity of PD-1 can successfully reduce tumor load and has been widely used in the clinical treatment of various tumors.

The immune imbalance in patients with sepsis has many similarities tumors. PD-1 and PD-L1 are key mediators in T cell depletion in sepsis patients. Animal models have shown that blocking PD-1 or PD-L1 can prevent T cell death, regulate cytokine production, reduce organ dysfunction and reduce death in sepsis. Previous study showed the clinical safety of anti-PD-1 antibody in sepsis patients through randomized, placebo-controlled trials.

Thymosin has also been proved to regulate cellular immunity in sepsis patients. Some studies have shown that thymosin can significantly reduce the mortality of sepsis patients. At present, phase III clinical research is in progress to further clarify the role of thymosin in patients with sepsis. The purpose of this study was to investigate the efficacy of PD-1 and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients
Estimated Study Start Date : February 10, 2020
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : October 31, 2020

Arm Intervention/treatment
Experimental: PD-1 group
Anti-PD-1 antibody, 200mg, IV, one time
Drug: PD-1 blocking antibody+standard treatment
After randomization, PD-1 blocking antibody 200mg iv, one time. Standard treatment is according to the protocol of treatment of 2019-nCoV infection

Experimental: thymosin group
Thymosin, 1.6 mg sc qd, last for 5 days
Drug: Thymosin+standard treatment
Thymosin 1.6 mg sc qd, last for 5 days. Standard treatment is according to the protocol of treatment of 2019-nCoV infection

Placebo Comparator: control group
stand treatment
Other: standard treatment
Standard treatment is according to the protocol of treatment of 2019-nCoV infection




Primary Outcome Measures :
  1. lung injury score [ Time Frame: 7 days ]
    proportion of lung injury score decreased 1 or more points


Secondary Outcome Measures :
  1. absolute lymphocyte counts [ Time Frame: 7, 14 and 28 days ]
    lymphocyte counts at day 7, 14 and 28 after randimization

  2. serum level of CRP, PCT and IL-6 [ Time Frame: 3, 7 and 14 days ]
    serum level of CRP, PCT and IL-6 at day 3,7 and 14 after randimization

  3. SOFA score [ Time Frame: 7 days ]
    SOFA score at Day 7, with scores range from 0 to 24 and higher score means worse outcome

  4. all cause mortality rate [ Time Frame: 28 days ]
    died at day 28

  5. ventilation free days [ Time Frame: 28 days ]
  6. ICU free days [ Time Frame: up to 28 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult SARI patients with 2019-ncov infection confirmed by PCR;
  2. Absolute value of lymphocytes < 0. 6x 109/L;
  3. Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP>=5cmH2O))

Exclusion Criteria:

  1. Age < 18
  2. Pregnant
  3. Allergic to experimental drugs
  4. The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor);
  5. COPD or end-stage lung disease requires home oxygen therapy
  6. Expected survival time not exceeding 48 hours
  7. Participated in other clinical intervention trials within the last 3 months
  8. Autoimmune diseases
  9. A history of organ, bone marrow or hematopoietic stem cell transplantation 10. Received radiotherapy and chemotherapy for malignant tumor within 6 months

11.HIV infected patients or diagnosed with acquired immunodeficiency within the past year (CD4 T cells <=200/mm3) 12. Patients receiving anti-hcv treatment 13.90 days of retinal detachment or eye surgery 14. Permanent blindness in one eye 15. History of iritis, endophthalmitis, scleral inflammation or retinitis 16. The competent physician considered it inappropriate to participate in the study

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Responsible Party: Jianfeng Xie, Director Assistant of ICU, Southeast University, China
ClinicalTrials.gov Identifier: NCT04268537    
Other Study ID Numbers: 2020YFC0841300-03
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: February 13, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Jianfeng Xie, Southeast University, China:
2019-ncov
immunotherapy
PD-1
respiratory failure
Additional relevant MeSH terms:
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Antibodies
Antibodies, Blocking
Immunologic Factors
Physiological Effects of Drugs