Bacterial Pneumonia
Conditions
Keywords
Biologic Therapy
Brief summary
The purpose of this randomised, multicentre, double-blind, placebo-controlled, phase Ib/IIa study is to assess the safety, tolerability and efficacy of eASCs (Cx611) administered intravenously as adjunctive therapy, therefore in addition to standard of care (SoC) therapy, to patients with severe community-acquired bacterial pneumonia (sCABP). The completion of this study will contribute to the basic knowledge on stem cells and their mode-of-action, and has a large translational character, i.e. to document the safety and explore the efficacy of Cx611 in patients with sCABP.
Detailed description
The purpose of this randomised, multicentre, double-blind, placebo-controlled, phase Ib/IIa study is to assess the safety, tolerability and efficacy of eASCs (Cx611) administered intravenously as adjunctive therapy, therefore in addition to standard of care (SoC) therapy, to patients with severe community-acquired bacterial pneumonia (sCABP). The key objectives of this study are to: Primary objective: Investigate the safety profile of two allogeneic Cx611 80 mL infusions administered through a central line within 3 days (on days 1 and 3) at a dose of 160 million cells each (320 million cells total) and to monitor any adverse event and potential immunological host responses against the administered cells during 90 days of follow-up after the first infusion. Secondary objective: Explore the clinical efficacy of Cx611 in terms of a reduction of the duration of mechanical ventilation and/or need for vasopressors and/or improved survival, and/or clinical cure of the sCABP, and other efficacy-related endpoints.
Interventions
BIOLOGICALCx611
Two intravenous infusions, one on day 1 and another one on day 3.
OTHERPlacebo
Two intravenous infusions, one on day 1 and another one on day 3.
Sponsors
European Commission
Centre Hospital Regional Universitaire de Limoges
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Hospital San Carlos, Madrid
Tigenix S.A.U.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult subjects of either gender (aged ≥18 years and ≤80 years old.) 2. Body weight between 50 kg and 100 kg. 3. Clinical diagnosis of acute (developed within ≤21 past days) community acquired bacterial pneumonia based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s. 4. Subjects with pneumonia of sufficient severity requiring ICU management and with at least one of the two following major criteria of severity present for less than 18 hours: 1. Requiring invasive mechanical ventilation for respiratory failure due to pneumonia, or 2. Requiring treatment with vasopressors (i.e., dopamine \>5 mcg/kg/min or any dose of epinephrine, norepinephrine, phenylephrine or vasopressin) for at least 2 hours to maintain or attempt to maintain systolic blood pressure (SBP) \>90 mm Hg (or mean arterial pressure \[MAP\] \>70 mm Hg) after adequate fluid resuscitation (i.e. for shock). NOTE: Patients that are for 18 hours or more under high flow nasal cannula (HFNC) at ≥50 liters per minute and FiO2 ≥0.6 or under non-mechanical ventilation (NMV) are not eligible for the study 5. Female subject of no childbearing potential i.e. non-fertile, pre-menarche, permanently sterile (i.e. underwent hysterectomy, bilateral salpingectomy or bilateral ovariectomy) or post-menopausal (history of no menses for at least 12 months without an alternative medical cause) or Woman of childbearing potential\* with a negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin \[hCG\]) and agree to use an adequate method of contraception for three months after the last dose of the IMP according to her preferred and usual life style. Adequate methods of female contraception for this study are: sexual abstinence (refraining from heterosexual intercourse), hormonal contraception (both progesterone-only or combined oestrogen and progesterone; both with inhibition of ovulation or where inhibition of ovulation is not the primary mechanism of action), intra-uterine device, bilateral tubal occlusion, condom use by male sexual partner(s) or medically-assessed successfully vasectomized male sexual partner(s). \*A woman of childbearing potential is a woman between menarche and post-menopause (history of no menses for at least 12 months without an alternative medical cause) unless she has undergone hysterectomy, bilateral salpingectomy or bilateral ovariectomy Male subject agreeing to use one of the following methods of birth control according to his preferred and usual life style for three months after the last dose of the IMP: sexual abstinence (refraining from heterosexual intercourse), use of condoms or medically-assessed successful vasectomy , or having a female sexual partner(s) who is using an adequate method of contraception as described above. 6. Signed informed consent provided by the participant, the relatives or the designated legal representative according to local guidelines.
Exclusion criteria
A patient will not be included in the study if he/she meets ANY of the following criteria: 1. Subjects with Hospital acquired (HAP)-, Health Care acquired (HCAP)- or Ventilator associated-pneumonia (VAP). 2. Subjects with pneumonia exclusively of viral or fungal origin\*. Subjects with bacterial pneumonia co-infected with viruses and/or other microorganisms may be entered into the study. \*Due to the short time window (up to 18 hours) between fulfillment of severity criteria (i.e. initiation of invasive mechanical ventilation or vasopressors administration, whichever comes first) and the start of the first dose of study treatment, patients with a pneumonia of suspected bacterial origin by any established standard diagnostic method routinely applied at the study site (e.g. urinary antigen test, rt-PCR) can be entered into the study (confirmation of bacterial origin must be obtained afterwards). 3. Subjects with known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia. 4. Subjects with an aspiration pneumonia. 5. Subjects with known active tuberculosis. 6. Subjects with a history of post-obstructive pneumonia. 7. Subjects with cystic fibrosis. 8. Subjects with any chronic lung disease requiring oxygen therapy at home. 9. Presence of infection in another organ location caused by same pathogen (e.g. pneumococcal meningitis in the context of pneumococcal pneumonia). 10. Subjects expected to have rapidly fatal disease within 72 hours after randomisation. 11. Inability to maintain a mean arterial pressure ≥50 mmHg prior to screening despite the presence of vasopressors and intravenous fluids. 12. Subjects not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases. 13. Subjects with a history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies. 14. Subjects with known primary immunodeficiency disorder or with HIV infection and acquired immune deficiency syndrome (AIDS) with CD4 count \<200 cells/mm\^3 or not receiving highly active antiretroviral therapy (HAART) for HIV. 15. Subjects receiving immunosuppressant therapy (including chronic treatment with anti-tumour necrosis factor alpha (TNFα ) or on chronic high doses of steroids (single administration of ≥2 mg/kg body weight or 20 mg/day of prednisone or equivalent for ≥2 weeks). 16. Chronic granulocytopenia, not thought to be due to sepsis, as evidenced by an absolute neutrophil count \<500 per µL\>21 days prior to onset of pneumonia symptoms. 17. Subjects who received stem cell therapy, or allogenic transplantation (organ or bone marrow transplant) within the past 6 months. 18. Subjects receiving treatment with a biological agent (e.g. antibodies, cells), immunotherapy or plasma exchange treatment within the last 8 weeks. 19. Subjects currently receiving, or having received another investigational medication within 90 days prior to start of the study (or 5 half-lives of the investigational compound, whichever is longer). 20. Known allergies or hypersensitivity to Penicillin or Streptomycin and/or any component of CryoStor® CS10. 21. Subjects with a known liver function impairment associated with liver cirrhosis (Child Pugh C) or known oesophageal varices. 22. Subjects hospitalised within the previous 15 days. 23. Conditions resulting in a New York Heart Association or Canadian Cardiovascular Society Class IV functional status. 24. End-stage neuromuscular disorders (e.g. motor neuron diseases, myasthenia gravis, etc.) or cerebral disorders that impair weaning. 25. Patients with quadriplegia (traumatic or otherwise).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 90 | — |
| Number of Participants With Adverse Events of Special Interest (AESI) | Baseline up to Day 90 | AESIs are predefined adverse events (AEs) that required close monitoring and prompt reporting to the sponsor. Protocol-specific AEs considered as AESI for this study are thromboembolic events and hypersensitivity reactions such as anaphylaxis. |
| Number of Participants With Hypersensitivity Reactions | Baseline up to Day 90 | Hypersensitivity reactions included anaphylaxis (changes in systolic and diastolic blood pressure, core temperature, respiratory rate \[non-ventilated participants\], heart rate), episodes of skin reactions and signs and symptoms of respiratory distress, which require therapeutic intervention including drugs and/or changes in mechanical ventilation setting. Number of participants with hypersensitivity reactions were reported for this outcome measure. |
| Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1 | Day 1 | — |
| Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3 | Day 3 | — |
| Number of Participants With Markedly Abnormal Laboratory Values | Baseline up to Day 90 | — |
| Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | At Days 1, 14, and 90 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to End of Invasive and/or Non-invasive Mechanical Ventilation | Baseline up to Day 29 | Time in days, from the start date of invasive or non-invasive mechanical ventilation to the first stop date of invasive or non-invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Time to End of Vasopressors Treatment | Baseline up to Day 29 | Time in days, from the start date of vasopressors treatment to the first stop date of vasopressors treatment (that is, first time the participant ends vasopressors treatment), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10, 14, and 29 | Cure:complete pneumonia resolution at baseline(BL),no new pneumonia symptoms/complications attributable.Non-response:failure related/unrelated to pneumonia:persistence/progression of BL signs/symptoms of pneumonia;BL radiographic abnormalities after atleast 2 days of treatment;development of new pulmonary/extra pulmonary findings consistent with active infection/development of new pulmonary infection/extrapulmonary infection requiring antimicrobial therapy;persistence/progression of BL signs/symptoms of severe sepsis;development of new signs/symptoms of severe sepsis;death due to sepsis.Non-response-failure unrelated to pneumonia:any cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia(e.g.myocardial infarction, pulmonary thromboembolism, sepsis of urinary origin etc).Indeterminate:extenuating circumstances precluding classification to one of the above. |
| Time to sCABP Clinical Cure | Baseline up to Day 29 | Cure is defined as complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Duration of Antibiotic Treatment | Baseline up to Day 29 | — |
| Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Days 14, 29, and 90 | Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. |
| Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments | Baseline up to Day 90 | Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrates or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| 28-day All-cause Mortality | Day 28 | — |
| 28-day sCABP-associated Mortality | Day 28 | — |
| Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | At Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Survival data for percentage of participants at Baseline and at Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 was assessed and reported. |
| Mechanical Ventilation and Vasopressors Treatment-free Days | Baseline up to Day 28 | Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Number of days when participants were alive and free from mechanical ventilation and vasopressors were reported. |
| Time to Discharge From Intensive Care Unit (ICU) | Baseline up to Day 730 | Time to discharge from ICU was defined, in days, as the time between informed consent date and the date of discharge from the ICU. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Time to Discharge From Hospital | Baseline up to Day 730 | Time to discharge from hospital was defined, in days, as the time between informed consent date and the date of discharge from the hospital. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Length of Stay (LOS) in ICU and Hospital After Randomization | Baseline up to Day 730 | — |
| Number of ICU-free Days | Baseline up to Day 29 | ICU-free days will be defined as the number of days during which the participant was not in ICU, starting from the randomization date, to Day 29, or day of discontinuation. |
| Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU | Baseline up to Day 29 | The total SOFA Score is a composite of six sub scores representing the degree of dysfunction of six organ systems: Respiratory, Cardiovascular, Liver, Renal, Coagulation and Central Nervous System. Each organ system sub score ranges from 0 to 4 points. The total SOFA Score is the sum of the six-organ system sub scores. Accordingly, the total SOFA Score may range from a minimum score of 0 to a maximum score of 24. Higher scores indicate greater degree of dysfunction. |
| Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, and 29 | Number of participants with chest X-ray assessment compared to the previous assessment were assessed and reported. Number of participants which showed improvement, remission, stabilization, and worsening compared to previous CXR were reported. Cumulative data is reported only for participants who were assessed from Day 8-10. |
| Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) | Baseline up to Day 7 | — |
| Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion | Day 3: 0 to 12 hours post-IMP infusion | — |
| Number Participants Using Rescue Antibiotics | Baseline up to Day 29 | Any new intravenous antibiotic for CABP indication that was started after Day 1 and before Day 29 was considered a rescue antibiotic. |
| Time to Death | Baseline up to Day 90 | Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
| Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29 | Day 29 | Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Percentage of participants who were alive and free of both mechanical ventilation and vasopressors at Day 29 were reported. |
| Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29 | Day 29 | — |
| Number of Ventilator Free Days (VeFD) | Baseline up to Day 28 | VeFD are defined as one point for each day during the measurement period that participants are both alive and free from mechanical ventilation. |
| Percentage of Participants Alive and Free of Vasopressors at Day 29 | Day 29 | — |
| Number of Vasopressor Treatment-free Days (VaFD) | Baseline up to Day 28 | VaFD over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors. |
| Time to End of Invasive Mechanical Ventilation | Baseline up to Day 29 | Time in days, from the start date of invasive mechanical ventilation to the first stop date of invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported. |
Countries
Belgium, France, Italy, Lithuania, Norway, Spain
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in Belgium, France, Lithuania, and Spain from 30 Jan 2017 to 07 July 2020.
Pre-assignment details
Adult participants with severe community-acquired bacterial pneumonia (sCABP) and admitted to the intensive care unit (ICU) were enrolled in 1 of the 2 treatment groups to receive Cx611 or placebo on Days 1 and 3.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3. | 41 |
| Cx611 160 mL Participants received SoC therapy followed by two 80 mL central line infusions of Cx611, intravenously, on Days 1 and 3 at a fixed dose of 160 million eASCs (320 million cells total). | 42 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 12 |
| Overall Study | Enrolled, not treated | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Participant doesn't want to come back to the hospital for the visit | 2 | 0 |
| Overall Study | Visit 11 not done by mistake | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Cx611 160 mL | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 11.24 | 62.3 years STANDARD_DEVIATION 10.84 | 63.4 years STANDARD_DEVIATION 10.43 |
| Race/Ethnicity, Customized Asian/Oriental | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 28 Participants | 59 Participants | 31 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Latino | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 12 Participants | 18 Participants | 6 Participants |
| Region of Enrollment Belgium | 7 Participants | 19 Participants | 12 Participants |
| Region of Enrollment France | 12 Participants | 18 Participants | 6 Participants |
| Region of Enrollment Lithuania | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 22 Participants | 45 Participants | 23 Participants |
| Sex: Female, Male Female | 14 Participants | 29 Participants | 15 Participants |
| Sex: Female, Male Male | 28 Participants | 54 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 41 | 13 / 42 |
| other Total, other adverse events | 41 / 41 | 42 / 42 |
| serious Total, serious adverse events | 20 / 41 | 24 / 42 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 37 Participants |
| Cx611 160 mL | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 40 Participants |
Primary
Number of Participants With Adverse Events of Special Interest (AESI)
AESIs are predefined adverse events (AEs) that required close monitoring and prompt reporting to the sponsor. Protocol-specific AEs considered as AESI for this study are thromboembolic events and hypersensitivity reactions such as anaphylaxis.
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events of Special Interest (AESI) | 9 Participants |
| Cx611 160 mL | Number of Participants With Adverse Events of Special Interest (AESI) | 7 Participants |
Primary
Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90
Time frame: At Days 1, 14, and 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here number analyzed are the participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 14 | 4 Participants |
| Placebo | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 1 | 6 Participants |
| Placebo | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 90 | 4 Participants |
| Cx611 160 mL | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 1 | 4 Participants |
| Cx611 160 mL | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 14 | 5 Participants |
| Cx611 160 mL | Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90 | Participants with Anti-HLA/Donor Antibodies at Day 90 | 4 Participants |
Primary
Number of Participants With Hypersensitivity Reactions
Hypersensitivity reactions included anaphylaxis (changes in systolic and diastolic blood pressure, core temperature, respiratory rate \[non-ventilated participants\], heart rate), episodes of skin reactions and signs and symptoms of respiratory distress, which require therapeutic intervention including drugs and/or changes in mechanical ventilation setting. Number of participants with hypersensitivity reactions were reported for this outcome measure.
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hypersensitivity Reactions | 1 Participants |
| Cx611 160 mL | Number of Participants With Hypersensitivity Reactions | 0 Participants |
Primary
Number of Participants With Markedly Abnormal Laboratory Values
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Markedly Abnormal Laboratory Values | 0 Participants |
| Cx611 160 mL | Number of Participants With Markedly Abnormal Laboratory Values | 0 Participants |
Primary
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1
Time frame: Day 1
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1 | 3 Participants |
| Cx611 160 mL | Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1 | 7 Participants |
Primary
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3
Time frame: Day 3
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3 | 5 Participants |
| Cx611 160 mL | Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3 | 4 Participants |
Secondary
28-day All-cause Mortality
Time frame: Day 28
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | 28-day All-cause Mortality | 6 Participants |
| Cx611 160 mL | 28-day All-cause Mortality | 8 Participants |
Secondary
28-day sCABP-associated Mortality
Time frame: Day 28
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | 28-day sCABP-associated Mortality | 0 Participants |
| Cx611 160 mL | 28-day sCABP-associated Mortality | 1 Participants |
Secondary
Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU
The total SOFA Score is a composite of six sub scores representing the degree of dysfunction of six organ systems: Respiratory, Cardiovascular, Liver, Renal, Coagulation and Central Nervous System. Each organ system sub score ranges from 0 to 4 points. The total SOFA Score is the sum of the six-organ system sub scores. Accordingly, the total SOFA Score may range from a minimum score of 0 to a maximum score of 24. Higher scores indicate greater degree of dysfunction.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure. Here, number analyzed are the participants who were evaluable for the outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU | Baseline | 7.9 Score on a scale | Standard Deviation 2.39 |
| Placebo | Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU | Change at Day 29 | -6.1 Score on a scale | Standard Deviation 3.3 |
| Cx611 160 mL | Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU | Baseline | 8.5 Score on a scale | Standard Deviation 3.01 |
| Cx611 160 mL | Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU | Change at Day 29 | -5.7 Score on a scale | Standard Deviation 3.95 |
Secondary
Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)
Time frame: Baseline up to Day 7
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here number analyzed n are the participants who were evaluable for this outcome measure at given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) | Baseline | 131.6 P/F ratio | Standard Deviation 55.14 |
| Placebo | Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) | Change at Day 7 | 74.6 P/F ratio | Standard Deviation 97.2 |
| Cx611 160 mL | Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) | Baseline | 278.6 P/F ratio | Standard Deviation 981.67 |
| Cx611 160 mL | Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) | Change at Day 7 | 78.4 P/F ratio | Standard Deviation 68.57 |
Secondary
Duration of Antibiotic Treatment
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Antibiotic Treatment | 9.0 days |
| Cx611 160 mL | Duration of Antibiotic Treatment | 8.0 days |
Secondary
Length of Stay (LOS) in ICU and Hospital After Randomization
Time frame: Baseline up to Day 730
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Length of Stay (LOS) in ICU and Hospital After Randomization | Length of stay in ICU | 11.1 days |
| Placebo | Length of Stay (LOS) in ICU and Hospital After Randomization | Length of stay in Hospital | 19.2 days |
| Cx611 160 mL | Length of Stay (LOS) in ICU and Hospital After Randomization | Length of stay in ICU | 12.3 days |
| Cx611 160 mL | Length of Stay (LOS) in ICU and Hospital After Randomization | Length of stay in Hospital | 19.3 days |
Secondary
Mechanical Ventilation and Vasopressors Treatment-free Days
Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Number of days when participants were alive and free from mechanical ventilation and vasopressors were reported.
Time frame: Baseline up to Day 28
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Mechanical Ventilation and Vasopressors Treatment-free Days | 19.0 days |
| Cx611 160 mL | Mechanical Ventilation and Vasopressors Treatment-free Days | 13.5 days |
Secondary
Number of ICU-free Days
ICU-free days will be defined as the number of days during which the participant was not in ICU, starting from the randomization date, to Day 29, or day of discontinuation.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of ICU-free Days | 14.0 days |
| Cx611 160 mL | Number of ICU-free Days | 5.5 days |
Secondary
Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment
Number of participants with chest X-ray assessment compared to the previous assessment were assessed and reported. Number of participants which showed improvement, remission, stabilization, and worsening compared to previous CXR were reported. Cumulative data is reported only for participants who were assessed from Day 8-10.
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, and 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure. Here, number analyzed are the participants who were evaluable for the outcome measure at given time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 3: Compared to previous chest X-ray | 17 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 1: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 1: Compared to previous chest X-ray | 7 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 1: Compared to previous chest X-ray | 2 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 2: Compared to previous chest X-ray | 9 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 2: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 2: Compared to previous chest X-ray | 17 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 2: Compared to previous chest X-ray | 8 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 3: Compared to previous chest X-ray | 19 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 3: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 1: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 3: Compared to previous chest X-ray | 1 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 4: Compared to previous chest X-ray | 14 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 4: Compared to previous chest X-ray | 1 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 4: Compared to previous chest X-ray | 15 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 4: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 5: Compared to previous chest X-ray | 5 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 5: Compared to previous chest X-ray | 2 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 5: Compared to previous chest X-ray | 7 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 5: Compared to previous chest X-ray | 6 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 6: Compared to previous chest X-ray | 11 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 6: Compared to previous chest X-ray | 1 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 6: Compared to previous chest X-ray | 15 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 6: Compared to previous chest X-ray | 2 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 7: Compared to previous chest X-ray | 8 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 7: Compared to previous chest X-ray | 0 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 7: Compared to previous chest X-ray | 7 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 7: Compared to previous chest X-ray | 3 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Days 8-10: Compared to previous chest X-ray | 8 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Days 8-10: Compared to previous chest X-ray | 3 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Days 8-10: Compared to previous chest X-ray | 11 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Days 8-10: Compared to previous chest X-ray | 5 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 14: Compared to previous chest X-ray | 10 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 14: Compared to previous chest X-ray | 1 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 14: Compared to previous chest X-ray | 5 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 14: Compared to previous chest X-ray | 5 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 29: Compared to previous chest X-ray | 3 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 29: Compared to previous chest X-ray | 3 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 29: Compared to previous chest X-ray | 2 Participants |
| Placebo | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 29: Compared to previous chest X-ray | 1 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 29: Compared to previous chest X-ray | 2 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 1: Compared to previous chest X-ray | 0 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 6: Compared to previous chest X-ray | 12 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 1: Compared to previous chest X-ray | 0 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Days 8-10: Compared to previous chest X-ray | 7 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 1: Compared to previous chest X-ray | 6 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 6: Compared to previous chest X-ray | 2 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 1: Compared to previous chest X-ray | 4 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 14: Compared to previous chest X-ray | 1 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 2: Compared to previous chest X-ray | 6 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 6: Compared to previous chest X-ray | 10 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 2: Compared to previous chest X-ray | 0 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Days 8-10: Compared to previous chest X-ray | 3 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 2: Compared to previous chest X-ray | 17 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 6: Compared to previous chest X-ray | 2 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 2: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 29: Compared to previous chest X-ray | 2 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 3: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 7: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 3: Compared to previous chest X-ray | 1 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 14: Compared to previous chest X-ray | 10 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 3: Compared to previous chest X-ray | 17 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 7: Compared to previous chest X-ray | 0 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 3: Compared to previous chest X-ray | 4 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 29: Compared to previous chest X-ray | 6 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 4: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 7: Compared to previous chest X-ray | 11 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 4: Compared to previous chest X-ray | 3 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 14: Compared to previous chest X-ray | 1 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 4: Compared to previous chest X-ray | 12 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 7: Compared to previous chest X-ray | 3 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 4: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 29: Compared to previous chest X-ray | 4 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Day 5: Compared to previous chest X-ray | 8 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Improvement at Days 8-10: Compared to previous chest X-ray | 9 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Day 5: Compared to previous chest X-ray | 2 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 14: Compared to previous chest X-ray | 3 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Stabilization at Day 5: Compared to previous chest X-ray | 9 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Remission at Days 8-10: Compared to previous chest X-ray | 3 Participants |
| Cx611 160 mL | Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment | Worsening at Day 5: Compared to previous chest X-ray | 5 Participants |
Secondary
Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion
Time frame: Day 3: 0 to 12 hours post-IMP infusion
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion | 31 Participants |
| Cx611 160 mL | Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion | 37 Participants |
Secondary
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29
Cure:complete pneumonia resolution at baseline(BL),no new pneumonia symptoms/complications attributable.Non-response:failure related/unrelated to pneumonia:persistence/progression of BL signs/symptoms of pneumonia;BL radiographic abnormalities after atleast 2 days of treatment;development of new pulmonary/extra pulmonary findings consistent with active infection/development of new pulmonary infection/extrapulmonary infection requiring antimicrobial therapy;persistence/progression of BL signs/symptoms of severe sepsis;development of new signs/symptoms of severe sepsis;death due to sepsis.Non-response-failure unrelated to pneumonia:any cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia(e.g.myocardial infarction, pulmonary thromboembolism, sepsis of urinary origin etc).Indeterminate:extenuating circumstances precluding classification to one of the above.
Time frame: Days 8 to 10, 14, and 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here number analyzed are the participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Cure) | 18 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Failure not resulting in death) | 8 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Missing) | 1 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Indeterminate) | 6 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Missing) | 1 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Cure) | 30 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Failure not resulting in death) | 1 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Indeterminate) | 11 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Indeterminate) | 0 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Missing) | 1 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Cure) | 24 Participants |
| Placebo | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Failure not resulting in death) | 5 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Cure) | 26 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Cure) | 21 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Indeterminate) | 9 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Indeterminate) | 3 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Failure not resulting in death) | 1 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 29 (Missing) | 0 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Failure not resulting in death) | 4 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Failure not resulting in death) | 6 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Indeterminate) | 4 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Cure) | 24 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Day 14 (Missing) | 1 Participants |
| Cx611 160 mL | Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 | Days 8 to 10 (Missing) | 0 Participants |
Secondary
Number of Vasopressor Treatment-free Days (VaFD)
VaFD over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors.
Time frame: Baseline up to Day 28
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Vasopressor Treatment-free Days (VaFD) | 24.0 days |
| Cx611 160 mL | Number of Vasopressor Treatment-free Days (VaFD) | 23.5 days |
Secondary
Number of Ventilator Free Days (VeFD)
VeFD are defined as one point for each day during the measurement period that participants are both alive and free from mechanical ventilation.
Time frame: Baseline up to Day 28
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Ventilator Free Days (VeFD) | 19.0 days |
| Cx611 160 mL | Number of Ventilator Free Days (VeFD) | 14.0 days |
Secondary
Number Participants Using Rescue Antibiotics
Any new intravenous antibiotic for CABP indication that was started after Day 1 and before Day 29 was considered a rescue antibiotic.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number Participants Using Rescue Antibiotics | 28 Participants |
| Cx611 160 mL | Number Participants Using Rescue Antibiotics | 32 Participants |
Secondary
Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29
Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Percentage of participants who were alive and free of both mechanical ventilation and vasopressors at Day 29 were reported.
Time frame: Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29 | 78.0 percentage of participants |
| Cx611 160 mL | Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29 | 64.3 percentage of participants |
Secondary
Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
Time frame: Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29 | 78.0 percentage of participants |
| Cx611 160 mL | Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29 | 66.7 percentage of participants |
Secondary
Percentage of Participants Alive and Free of Vasopressors at Day 29
Time frame: Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Alive and Free of Vasopressors at Day 29 | 85.4 percentage of participants |
| Cx611 160 mL | Percentage of Participants Alive and Free of Vasopressors at Day 29 | 76.2 percentage of participants |
Secondary
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure
Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection.
Time frame: Days 14, 29, and 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure. Here, number analyzed are the participants who were evaluable for the outcome measure at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 14: Recurrence | 5.6 percentage of participants |
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 14: Reinfection | 8.3 percentage of participants |
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 29: Recurrence | 0 percentage of participants |
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 29: Reinfection | 0 percentage of participants |
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 90: Recurrence | 0 percentage of participants |
| Placebo | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 90: Reinfection | 0 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 90: Recurrence | 0 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 14: Recurrence | 0 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 29: Reinfection | 0 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 14: Reinfection | 6.1 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 90: Reinfection | 0 percentage of participants |
| Cx611 160 mL | Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure | Day 29: Recurrence | 3.3 percentage of participants |
Secondary
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Survival data for percentage of participants at Baseline and at Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 was assessed and reported.
Time frame: At Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Baseline | 100.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 10 | 95.1 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 20 | 87.5 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 30 | 85.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 40 | 77.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 50 | 77.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 60 | 77.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 70 | 77.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 80 | 77.0 percentage of participants |
| Placebo | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 90 | 77.0 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 70 | 75.3 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Baseline | 100.0 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 50 | 75.3 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 10 | 88.1 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 90 | 71.5 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 20 | 80.7 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 60 | 75.3 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 30 | 80.7 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 80 | 75.3 percentage of participants |
| Cx611 160 mL | Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Day 40 | 80.7 percentage of participants |
Secondary
Time to Death
Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Death | NA days |
| Cx611 160 mL | Time to Death | NA days |
Secondary
Time to Discharge From Hospital
Time to discharge from hospital was defined, in days, as the time between informed consent date and the date of discharge from the hospital. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 730
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Discharge From Hospital | 19.2 days |
| Cx611 160 mL | Time to Discharge From Hospital | 18.3 days |
Secondary
Time to Discharge From Intensive Care Unit (ICU)
Time to discharge from ICU was defined, in days, as the time between informed consent date and the date of discharge from the ICU. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 730
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Discharge From Intensive Care Unit (ICU) | 11.1 days |
| Cx611 160 mL | Time to Discharge From Intensive Care Unit (ICU) | 13.0 days |
Secondary
Time to End of Invasive and/or Non-invasive Mechanical Ventilation
Time in days, from the start date of invasive or non-invasive mechanical ventilation to the first stop date of invasive or non-invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to End of Invasive and/or Non-invasive Mechanical Ventilation | 6.3 days |
| Cx611 160 mL | Time to End of Invasive and/or Non-invasive Mechanical Ventilation | 4.7 days |
Secondary
Time to End of Invasive Mechanical Ventilation
Time in days, from the start date of invasive mechanical ventilation to the first stop date of invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to End of Invasive Mechanical Ventilation | 7.7 days |
| Cx611 160 mL | Time to End of Invasive Mechanical Ventilation | 8.3 days |
Secondary
Time to End of Vasopressors Treatment
Time in days, from the start date of vasopressors treatment to the first stop date of vasopressors treatment (that is, first time the participant ends vasopressors treatment), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to End of Vasopressors Treatment | 2.1 days |
| Cx611 160 mL | Time to End of Vasopressors Treatment | 2.0 days |
Secondary
Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments
Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrates or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 90
Population: The safety population included all randomized participants who received at least one dose of the study treatment. Here, overall number of participants analyzed are those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments | NA days |
| Cx611 160 mL | Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments | NA days |
Secondary
Time to sCABP Clinical Cure
Cure is defined as complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time frame: Baseline up to Day 29
Population: The safety population included all randomized participants who received at least one dose of the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to sCABP Clinical Cure | 13.0 days |
| Cx611 160 mL | Time to sCABP Clinical Cure | 9.5 days |