Drug-resistantPhase 1/2NCT04544215
A Clinical Study of Mesenchymal Progenitor Cell Exosomes Nebulizer for the Treatment of Pulmonary Infection
A Phase 1/2 study testing Dosage 1 of MPCs-derived exosomes, Dosage 2 of MPCs-derived exosomes and No MPCs-derived exosomes in people with Drug-resistant, run by Ruijin Hospital at 1 site in China.
Trial summary
Evaluate the efficacy and safety of haMPC-Exos treatment with pulmonary infection caused by gram-negative bacilli resistant to carbapenems. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Drug-resistant
- What is being tested?
- Dosage 1 of MPCs-derived exosomes, Dosage 2 of MPCs-derived exosomes and No MPCs-derived exosomes
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2020to 1 Mar 2025
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Willingness of study participant to accept this treatment arm, and signed informed consent; 2.Male or female, aged at 18 years (including) to 75 years old; 3.Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), was diagnosed within 48 h. The diagnosis must simultaneously comply with the three clinical and radiological criteria described below, which occurred more than 2 d (48 h) after hospitalization, within 7 d after discharge (HAP) or at least 2 d (48 h) after mechanical ventilation (VAP):
- The patients had at least one of the following clinical manifestations:
- New or deteriorating pulmonary symptoms or signs, such as cough, dyspnea, shortness of breath (e.g., respiratory rate higher than 25 beats/min), expectoration or need for mechanical ventilation;
- Hypoxemia (e.g., when subjects breathe room air at standard atmospheric pressure, the partial pressure of oxygen measured as lower than 60 mmHg by arterial blood gas [ABG], or the ratio of partial pressure of oxygen to fraction of inspired oxygen [PaO2/FiO2] deteriorated);
- According to the deterioration of oxygenation (ABG or PaO2/FiO2), the support system for the ventilator should be replaced urgently to strengthen oxygenation, or the positive end-expiratory pressure level should be changed;
- Aspirable respiratory secretions newly appeared;
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- The patients had at least one of the following signs:
- Confirmed fever (e.g., body temperature ≥ 38.4℃);
- Hypothermia (e.g., body temperature ≤ 35℃);
- Total peripheral white blood cell (WBC) count ≥ 11 × 109/L;
- Leukopenia, and total WBC ≤ 4 × 109/L;
- Immature neutrophils (rod-shaped nuclear cells) > 15% was observed on peripheral blood smears;
- The chest X-ray of the patients showed new or progressive infiltration, and pneumonia was considered.
- 4.The pathogenic test of the lower respiratory tract specimens revealed carbapenem-resistant Gram-negative bacilli (Pseudomonas aeruginosa, Klebsiella pneumoniae or Acinetobacter baumannii), which were consistent with the drug resistance spectrum and intermediate or resistant to all carbapenem antibiotics, namely, the minimum inhibitory concentration (MIC) of meropenem or imipenem ≥ 2 μg/ml (2 μg/ml was intermediate and 4 μg/ml was drug-resistant). The MIC of ertapenem ≥ 1 μg/ml, of which 1 μg/ml was intermediate and ≥ 2 μg/ml was drug-resistant.
Who cannot join
- 1.Patients with severe allergic constitution or positive skin test result for test products; 2.Confirmed or suspected community acquired pneumonia (CAP)； 3.Confirmed or suspected pneumonia caused by mycoplasma, chlamydia, legionella, viruses, fungi or parasites; 4.HAP/VAP caused by obstruction, including lung cancer (or other malignant disease that causes lung obstruction) or other known obstructions; 5.Active immunosuppression, it is defined as receiving immunosuppressive drugs or under medical conditions associated with immunodeficiency. Including: 1) HIV (AIDS or CD4 < 200 cells/mm3); 2) received chemotherapy within 6 weeks before randomization; 3) immunosuppressive therapy, including maintenance glucocorticoid therapy (> 40 mg/day Prednisolone equivalent dose); 4) absolute neutrophil count < 500 mg/mm3; additional condition for inclusion: 1) Short-term (within one week) systemic (intravenous or oral) steroid therapy, using steroids for the treatment of skin disorders; 6.History of epilepsy and requirement for continuous anticonvulsant treatment or anticonvulsant treatment received within the last 3 years; 7.Undergoing hemodialysis or peritoneal dialysis; 8.Estimated or actual rate of creatinine clearance < 15 ml/min; 9.It is expected that any of the following drugs will be used during the study: Within 2 weeks before screening, or continuous use of valproic acid or divalproex sodium; 5-selective serotonin reuptake inhibitor, tricyclic antidepressant, 5-HT1 receptor agonist (triptans) or monoamine oxidase inhibitor; monoamine oxidase inhibitor (MAOIs) (or use of MAOIs within 2 weeks before screening) pethidine; buspirone; traditional Chinese medicine or herbal medicine; 10.Lung transplantation； 11.Bone marrow transplantation； 12.History of deep venous thrombosis or pulmonary embolism within the last 3 months; 13.Undergoing ECMO or high-frequency oscillatory ventilation support; 14.The estimated survival time <8 days; 15.HIV, viral hepatitis type B，viral hepatitis type C，or syphilis infection; 16.Period of pregnancy or lactation, or planned pregnancy within 6 months; 17.Incapable of understanding study protocol; 18.Any condition of unsuitable for the study determined by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
About this study
Official title: A Clinical Study of Allogeneic Human Adipose-derived Mesenchymal Progenitor Cell Exosomes (haMPC-Exos) Nebulizer for the Treatment of Carbapenem-resistant Gram-negative Bacilli-induced Pulmonary Infection
Evaluate the efficacy and safety of haMPC-Exos treatment with pulmonary infection caused by gram-negative bacilli resistant to carbapenems.
Read the detailed description
Pulmonary infection is a critical disease threatening human health. With the extensive use of antibiotics, the incidence of clinical drug resistance has been on the rise significantly in recent years. Once drug resistance occurs, we will see a high mortality rate due to scarce therapies and a poor prognosis. It is almost impossible to surmount the severe pulmonary infection caused by drug-resistant bacteria only by upgrading antibiotics. The commonly used supportive therapies clinically, such as glucocorticoids and immunomodulators, also lack forceful medical evidence. Therefore, it is urgent to explore new treatments.
Mesenchymal stem/progenitor cell exosomes are nano-sized vesicles secreted by mesenchymal stem/progenitor cells under certain conditions, which contain a lot of proteins, lipids and nucleic acids with tissue repair and immunomodulatory functions.
Mesenchymal stem/progenitor cell exosomes are nano-sized vesicles secreted by mesenchymal stem/progenitor cells under certain conditions, which contain a lot of proteins, lipids and nucleic acids with tissue repair and immunomodulatory functions.
Currently, it has been confirmed that stem cells can visibly improve the pathological changes of lungs caused by infection, lighten pulmonary edema, reduce protein exudation, mitigate alveolar inflammation, and remove bacteria. Thus, it brings new hope for the treatment of pulmonary infection caused by extensively drug-resistant bacteria.
Patients were treated, in the research project, with well-suited noninvasive haMPC-Exos aerosol inhalation, in an attempt to verify the efficacy and safety of haMPC-Exos treatment with pulmonary infection caused by gram-negative bacilli resistant to carbapenems.
- Conditions
- Drug-resistant
- Being tested
- Dosage 1 of MPCs-derived exosomes, Dosage 2 of MPCs-derived exosomes, No MPCs-derived exosomes
- Keywords
- human adipose-derived mesenchymal progenitor cell exosomes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dosage 1 of MPCs-derived exosomesBiological
7 times aerosol inhalation of MPCs-derived exosomes (8.0*108 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7).
Dosage 2 of MPCs-derived exosomesBiological
7 times aerosol inhalation of MPCs-derived exosomes (16.0*108 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7).
No MPCs-derived exosomesBiological
No aerosol inhalation of MPCs-derived exosomes
| Study group | Role | What they receive |
|---|---|---|
| MPCs-derived exosomes Dosage 1 | Experimental | low-dose group Receives: Biological: Dosage 1 of MPCs-derived exosomes |
| MPCs-derived exosomes Dosage 2 | Experimental | high-dose group Receives: Biological: Dosage 2 of MPCs-derived exosomes |
| No exosomes | Placebo comparator | No MPCs-derived exosomes Receives: Biological: No MPCs-derived exosomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Measures:
1.Clinical cure rate on the 8th d
Measured: Up to 8 days
Secondary outcomes (7)
1.Bacterial clearance rate on the 8th d;
Bacterial clearance rate on the 8th d
Measured: Up to 8 days
2.Mortality on the 28th and 90th d;
Mortality on the 28th and 90th d
Measured: Up to 28-90 days
3.Recurrence rate after cure within 28 d;
Recurrence rate after cure within 28 d
Measured: Up to 28 days
4.Secondary infection rate of other pathogenic bacteria after cure within 28 d;
Secondary infection rate of other pathogenic bacteria after cure within 28 d
Measured: Up to 28 days
5.Duration of mechanical ventilation within 28 d;
Duration of mechanical ventilation within 28 d
Measured: Up to 28 days
6.Length of ICU stay (d) within 28 d;
Length of ICU stay (d) within 28 d
Measured: Up to 28 days
7.Incidence of adverse reactions at the end of treatment and 28 d after initial treatment.
Incidence of adverse reactions at the end of treatment and 28 d after initial treatment.
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 posted10 Sep 2020
- Study start1 Jul 2020
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Why it stopped: Due to the COVID-19 pandemic, patient enrollment was slower than expected. After enrolling 26 patients, the trial was suspended as our partner company stopped producing haMPC-Exos.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-resistantStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai AbelZeta Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04544215
- Sponsor's protocol ID
- MEXDR
- Status last verified
- May 2024
- First submitted
- 3 Sep 2020
- Last updated
- 22 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of Allogeneic Human Adipose-derived Mesenchymal Progenitor Cell Exosomes (haMPC-Exos) Nebulizer for the Treatment of Carbapenem-resistant Gram-negative Bacilli-induced Pulmonary Infection
- ClinicalTrials.gov ID
- NCT04544215
- Acronym / sponsor ID
- MEXDR
- Conditions
- Drug-resistant
- Keywords
- human adipose-derived mesenchymal progenitor cell exosomes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Due to the COVID-19 pandemic, patient enrollment was slower than expected. After enrolling 26 patients, the trial was suspended as our partner company stopped producing haMPC-Exos.
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Collaborators
- Shanghai AbelZeta Ltd.
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 10 Sep 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.
Evaluate the efficacy and safety of haMPC-Exos treatment with pulmonary infection caused by gram-negative bacilli resistant to carbapenems.
Detailed description
Pulmonary infection is a critical disease threatening human health. With the extensive use of antibiotics, the incidence of clinical drug resistance has been on the rise significantly in recent years. Once drug resistance occurs, we will see a high mortality rate due to scarce therapies and a poor prognosis. It is almost impossible to surmount the severe pulmonary infection caused by drug-resistant bacteria only by upgrading antibiotics. The commonly used supportive therapies clinically, such as glucocorticoids and immunomodulators, also lack forceful medical evidence. Therefore, it is urgent to explore new treatments.
Mesenchymal stem/progenitor cell exosomes are nano-sized vesicles secreted by mesenchymal stem/progenitor cells under certain conditions, which contain a lot of proteins, lipids and nucleic acids with tissue repair and immunomodulatory functions.
Mesenchymal stem/progenitor cell exosomes are nano-sized vesicles secreted by mesenchymal stem/progenitor cells under certain conditions, which contain a lot of proteins, lipids and nucleic acids with tissue repair and immunomodulatory functions.
Currently, it has been confirmed that stem cells can visibly improve the pathological changes of lungs caused by infection, lighten pulmonary edema, reduce protein exudation, mitigate alveolar inflammation, and remove bacteria. Thus, it brings new hope for the treatment of pulmonary infection caused by extensively drug-resistant bacteria.
Patients were treated, in the research project, with well-suited noninvasive haMPC-Exos aerosol inhalation, in an attempt to verify the efficacy and safety of haMPC-Exos treatment with pulmonary infection caused by gram-negative bacilli resistant to carbapenems.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MPCs-derived exosomes Dosage 1 | Experimental | Biological: Dosage 1 of MPCs-derived exosomeslow-dose group |
| MPCs-derived exosomes Dosage 2 | Experimental | Biological: Dosage 2 of MPCs-derived exosomeshigh-dose group |
| No exosomes | Placebo comparator | Biological: No MPCs-derived exosomesNo MPCs-derived exosomes |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 1.Willingness of study participant to accept this treatment arm, and signed informed consent; 2.Male or female, aged at 18 years (including) to 75 years old; 3.Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), was diagnosed within 48 h. The diagnosis must simultaneously comply with the three clinical and radiological criteria described below, which occurred more than 2 d (48 h) after hospitalization, within 7 d after discharge (HAP) or at least 2 d (48 h) after mechanical ventilation (VAP):
- The patients had at least one of the following clinical manifestations:
- The patients had at least one of the following signs:
- The chest X-ray of the patients showed new or progressive infiltration, and pneumonia was considered.
- 4.The pathogenic test of the lower respiratory tract specimens revealed carbapenem-resistant Gram-negative bacilli (Pseudomonas aeruginosa, Klebsiella pneumoniae or Acinetobacter baumannii), which were consistent with the drug resistance spectrum and intermediate or resistant to all carbapenem antibiotics, namely, the minimum inhibitory concentration (MIC) of meropenem or imipenem ≥ 2 μg/ml (2 μg/ml was intermediate and 4 μg/ml was drug-resistant). The MIC of ertapenem ≥ 1 μg/ml, of which 1 μg/ml was intermediate and ≥ 2 μg/ml was drug-resistant.
Key exclusion criteria (1 listed)
- 1.Patients with severe allergic constitution or positive skin test result for test products; 2.Confirmed or suspected community acquired pneumonia (CAP)； 3.Confirmed or suspected pneumonia caused by mycoplasma, chlamydia, legionella, viruses, fungi or parasites; 4.HAP/VAP caused by obstruction, including lung cancer (or other malignant disease that causes lung obstruction) or other known obstructions; 5.Active immunosuppression, it is defined as receiving immunosuppressive drugs or under medical conditions associated with immunodeficiency. Including: 1) HIV (AIDS or CD4 < 200 cells/mm3); 2) received chemotherapy within 6 weeks before randomization; 3) immunosuppressive therapy, including maintenance glucocorticoid therapy (> 40 mg/day Prednisolone equivalent dose); 4) absolute neutrophil count < 500 mg/mm3; additional condition for inclusion: 1) Short-term (within one week) systemic (intravenous or oral) steroid therapy, using steroids for the treatment of skin disorders; 6.History of epilepsy and requirement for continuous anticonvulsant treatment or anticonvulsant treatment received within the last 3 years; 7.Undergoing hemodialysis or peritoneal dialysis; 8.Estimated or actual rate of creatinine clearance < 15 ml/min; 9.It is expected that any of the following drugs will be used during the study: Within 2 weeks before screening, or continuous use of valproic acid or divalproex sodium; 5-selective serotonin reuptake inhibitor, tricyclic antidepressant, 5-HT1 receptor agonist (triptans) or monoamine oxidase inhibitor; monoamine oxidase inhibitor (MAOIs) (or use of MAOIs within 2 weeks before screening) pethidine; buspirone; traditional Chinese medicine or herbal medicine; 10.Lung transplantation； 11.Bone marrow transplantation； 12.History of deep venous thrombosis or pulmonary embolism within the last 3 months; 13.Undergoing ECMO or high-frequency oscillatory ventilation support; 14.The estimated survival time <8 days; 15.HIV, viral hepatitis type B，viral hepatitis type C，or syphilis infection; 16.Period of pregnancy or lactation, or planned pregnancy within 6 months; 17.Incapable of understanding study protocol; 18.Any condition of unsuitable for the study determined by investigators.
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 |
|---|---|---|
| Dosage 1 of MPCs-derived exosomes7 times aerosol inhalation of MPCs-derived exosomes (8.0*108 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7). | Biological | MPCs-derived exosomes Dosage 1 |
| Dosage 2 of MPCs-derived exosomes7 times aerosol inhalation of MPCs-derived exosomes (16.0*108 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7). | Biological | MPCs-derived exosomes Dosage 2 |
| No MPCs-derived exosomesNo aerosol inhalation of MPCs-derived exosomes | Biological | No exosomes |
Primary outcome
Primary Outcome Measures:
Time frame: Up to 8 days
1.Clinical cure rate on the 8th d
7 secondary outcomes
1.Bacterial clearance rate on the 8th d;
Time frame: Up to 8 days
2.Mortality on the 28th and 90th d;
Time frame: Up to 28-90 days
3.Recurrence rate after cure within 28 d;
Time frame: Up to 28 days
4.Secondary infection rate of other pathogenic bacteria after cure within 28 d;
Time frame: Up to 28 days
5.Duration of mechanical ventilation within 28 d;
Time frame: Up to 28 days
6.Length of ICU stay (d) within 28 d;
Time frame: Up to 28 days
7.Incidence of adverse reactions at the end of treatment and 28 d after initial treatment.
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 22 Jul 2024.
- Individual participant dataSharing planned: Yes
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dosage 1 of MPCs-derived exosomes, Dosage 2 of MPCs-derived exosomes and No MPCs-derived exosomes in people with Drug-resistant, run by Ruijin Hospital at 1 site in 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 14 inclusion and 1 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: paused, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Primary Outcome Measures: (time frame: Up to 8 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 22 Jul 2024.