2019 nCoV, PD-1Phase 2NCT04268537
Immunoregulatory Therapy for 2019-nCoV
A Phase 2 study testing PD-1 blocking antibody+standard treatment, Thymosin+standard treatment and standard treatment in people with 2019 nCoV, PD-1, run by Southeast University, China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 2019 nCoV, PD-1
- What is being tested?
- PD-1 blocking antibody+standard treatment, Thymosin+standard treatment and standard treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 10 Feb 2020to 31 Oct 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult SARI patients with 2019-ncov infection confirmed by PCR;
- Absolute value of lymphocytes < 0. 6x 109/L;
- 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))
Who cannot join
- Age < 18
- Pregnant
- Allergic to experimental drugs
- The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor);
- COPD or end-stage lung disease requires home oxygen therapy
- Expected survival time not exceeding 48 hours
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- Participated in other clinical intervention trials within the last 3 months
- Autoimmune diseases
- 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
About this study
Official title: Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients
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.
Read the 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.
- Conditions
- 2019 nCoV, PD-1
- Being tested
- PD-1 blocking antibody+standard treatment, Thymosin+standard treatment, standard treatment
- Keywords
- 2019-ncov, immunotherapy, PD-1, respiratory failure
- Medical subject headings
- Parkinson Disease 4, Autosomal Dominant Lewy Body, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 blocking antibody+standard treatmentDrug
After randomization, PD-1 blocking antibody 200mg iv, one time. Standard treatment is according to the protocol of treatment of 2019-nCoV infection
Thymosin+standard treatmentDrug
Thymosin 1.6 mg sc qd, last for 5 days. Standard treatment is according to the protocol of treatment of 2019-nCoV infection
standard treatmentOther
Standard treatment is according to the protocol of treatment of 2019-nCoV infection
| Study group | Role | What they receive |
|---|---|---|
| PD-1 group | Experimental | Anti-PD-1 antibody, 200mg, IV, one time Receives: Drug: PD-1 blocking antibody+standard treatment |
| thymosin group | Experimental | Thymosin, 1.6 mg sc qd, last for 5 days Receives: Drug: Thymosin+standard treatment |
| control group | Placebo comparator | stand treatment Receives: Other: standard treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
lung injury score
proportion of lung injury score decreased 1 or more points
Measured: 7 days
Secondary outcomes (6)
absolute lymphocyte counts
lymphocyte counts at day 7, 14 and 28 after randimization
Measured: 7, 14 and 28 days
serum level of CRP, PCT and IL-6
serum level of CRP, PCT and IL-6 at day 3,7 and 14 after randimization
Measured: 3, 7 and 14 days
SOFA score
SOFA score at Day 7, with scores range from 0 to 24 and higher score means worse outcome
Measured: 7 days
all cause mortality rate
died at day 28
Measured: 28 days
ventilation free days
Measured: 28 days
ICU free days
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start10 Feb 2020 (estimated)
- Primary completion30 Apr 2020 (estimated)
- Study completion31 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 2019 nCoV, PD-1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southeast University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianfeng Xie, Southeast University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04268537
- Sponsor's protocol ID
- 2020YFC0841300-03
- Status last verified
- Feb 2020
- First submitted
- 8 Feb 2020
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients
- ClinicalTrials.gov ID
- NCT04268537
- Acronym / sponsor ID
- 2020YFC0841300-03
- Conditions
- 2019 nCoV, PD-1
- Keywords
- 2019-ncov, immunotherapy, PD-1, respiratory failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Southeast University, ChinaUniversity, hospital or other
- Study start
- 10 Feb 2020 (estimated)
- Primary completion
- 30 Apr 2020 (estimated)
- Study completion
- 31 Oct 2020 (estimated)
- First posted
- 13 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PD-1 group | Experimental | Drug: PD-1 blocking antibody+standard treatmentAnti-PD-1 antibody, 200mg, IV, one time |
| thymosin group | Experimental | Drug: Thymosin+standard treatmentThymosin, 1.6 mg sc qd, last for 5 days |
| control group | Placebo comparator | Other: standard treatmentstand treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult SARI patients with 2019-ncov infection confirmed by PCR;
- Absolute value of lymphocytes < 0. 6x 109/L;
- 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))
Key exclusion criteria (10 listed)
- Age < 18
- Pregnant
- Allergic to experimental drugs
- The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor);
- COPD or end-stage lung disease requires home oxygen therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 blocking antibody+standard treatmentAfter randomization, PD-1 blocking antibody 200mg iv, one time. Standard treatment is according to the protocol of treatment of 2019-nCoV infection | Drug | PD-1 group |
| Thymosin+standard treatmentThymosin 1.6 mg sc qd, last for 5 days. Standard treatment is according to the protocol of treatment of 2019-nCoV infection | Drug | thymosin group |
| standard treatmentStandard treatment is according to the protocol of treatment of 2019-nCoV infection | Other | control group |
Primary outcome
lung injury score
Time frame: 7 days
proportion of lung injury score decreased 1 or more points
6 secondary outcomes
absolute lymphocyte counts
Time frame: 7, 14 and 28 days
serum level of CRP, PCT and IL-6
Time frame: 3, 7 and 14 days
SOFA score
Time frame: 7 days
all cause mortality rate
Time frame: 28 days
ventilation free days
Time frame: 28 days
ICU free days
Time frame: up to 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-1 blocking antibody+standard treatment, Thymosin+standard treatment and standard treatment in people with 2019 nCoV, PD-1, run by Southeast University, China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
lung injury score (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2020.