Trial Outcomes & Findings for Cx611-0204 SEPCELL Study (NCT NCT03158727)

Last Updated: 2022-04-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

84 participants

Primary outcome timeframe

Baseline up to Day 90

Results posted on

2022-04-06

Participant Flow

Participants took part in the study at 20 investigative sites in Belgium, France, Lithuania, and Spain from 30 Jan 2017 to 07 July 2020.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Overall Study STARTED	42	42
Overall Study Enrolled, Not Treated	1	0
Overall Study COMPLETED	25	23
Overall Study NOT COMPLETED	17	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Overall Study Withdrawal by Subject	2	6
Overall Study Death	11	12
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 Enrolled, not treated	1	0

Baseline Characteristics

Cx611-0204 SEPCELL Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).	Total n=83 Participants Total of all reporting groups
Age, Continuous	63.4 years STANDARD_DEVIATION 10.43 • n=5 Participants	61.1 years STANDARD_DEVIATION 11.24 • n=7 Participants	62.3 years STANDARD_DEVIATION 10.84 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Belgium	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment Spain	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Lithuania	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 90

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	37 Participants	40 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 90

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With Adverse Events of Special Interest (AESI)	9 Participants	7 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 90

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With Hypersensitivity Reactions	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1	3 Participants	7 Participants

PRIMARY outcome

Timeframe: Day 3

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3	5 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 90

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With Markedly Abnormal Laboratory Values	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
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	4 Participants
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	5 Participants
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	4 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 28

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Mechanical Ventilation and Vasopressors Treatment-free Days	19.0 days Interval 0.0 to 27.0	13.5 days Interval 0.0 to 25.0

SECONDARY outcome

Timeframe: Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29	78.0 percentage of participants	64.3 percentage of participants

SECONDARY outcome

Timeframe: Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29	78.0 percentage of participants	66.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 28

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

VeFD are defined as one point for each day during the measurement period that participants are both alive and free from mechanical ventilation.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Ventilator Free Days (VeFD)	19.0 days Interval 0.0 to 28.0	14.0 days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Percentage of Participants Alive and Free of Vasopressors at Day 29	85.4 percentage of participants	76.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 28

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

VaFD over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Vasopressor Treatment-free Days (VaFD)	24.0 days Interval 0.0 to 28.0	23.5 days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=33 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=39 Participants 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).
Time to End of Invasive Mechanical Ventilation	7.7 days Interval 4.6 to 11.5	8.3 days Interval 4.6 to 12.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=33 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=39 Participants 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).
Time to End of Invasive and/or Non-invasive Mechanical Ventilation	6.3 days Interval 3.3 to 10.3	4.7 days Interval 2.9 to 8.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=33 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=34 Participants 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).
Time to End of Vasopressors Treatment	2.1 days Interval 1.4 to 3.0	2.0 days Interval 1.0 to 2.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Days 8 to 10 (Cure)	18 Participants	21 Participants
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	6 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Days 8 to 10 (Indeterminate)	11 Participants	9 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Days 8 to 10 (Missing)	1 Participants	0 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 14 (Cure)	24 Participants	24 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 14 (Failure not resulting in death)	5 Participants	4 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 14 (Indeterminate)	6 Participants	4 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 14 (Missing)	1 Participants	1 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 29 (Cure)	30 Participants	26 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 29 (Failure not resulting in death)	1 Participants	1 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 29 (Indeterminate)	0 Participants	3 Participants
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29 Day 29 (Missing)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Time to sCABP Clinical Cure	13.0 days Interval 10.0 to 16.0	9.5 days Interval 8.0 to 14.0

SECONDARY outcome

Timeframe: Baseline up to Day 29

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=38 Participants 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).
Duration of Antibiotic Treatment	9.0 days Interval 2.0 to 29.0	8.0 days Interval 1.0 to 29.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=36 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=33 Participants 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).
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 14: Recurrence	5.6 percentage of participants	0 percentage of participants
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 14: Reinfection	8.3 percentage of participants	6.1 percentage of participants
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 29: Recurrence	0 percentage of participants	3.3 percentage of participants
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 29: Reinfection	0 percentage of participants	0 percentage of participants
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 90: Recurrence	0 percentage of participants	0 percentage of participants
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure Day 90: Reinfection	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=32 Participants 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).
Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments	NA days Median and 95% confidence interval could not be calculated because an insufficient number of participants had an event.	NA days Median and 95% confidence interval could not be calculated because an insufficient number of participants had an event.

SECONDARY outcome

Timeframe: Day 28

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
28-day All-cause Mortality	6 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 28

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
28-day sCABP-associated Mortality	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 40	77.0 percentage of participants Interval 60.4 to 87.3	80.7 percentage of participants Interval 65.0 to 89.8
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Baseline	100.0 percentage of participants Interval 100.0 to 100.0	100.0 percentage of participants Interval 100.0 to 100.0
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 10	95.1 percentage of participants Interval 81.9 to 98.8	88.1 percentage of participants Interval 73.7 to 94.9
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 20	87.5 percentage of participants Interval 72.6 to 94.6	80.7 percentage of participants Interval 65.0 to 89.8
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 30	85.0 percentage of participants Interval 69.5 to 93.0	80.7 percentage of participants Interval 65.0 to 89.8
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 50	77.0 percentage of participants Interval 60.4 to 87.3	75.3 percentage of participants Interval 58.9 to 85.9
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 60	77.0 percentage of participants Interval 60.4 to 87.3	75.3 percentage of participants Interval 58.9 to 85.9
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 70	77.0 percentage of participants Interval 60.4 to 87.3	75.3 percentage of participants Interval 58.9 to 85.9
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 80	77.0 percentage of participants Interval 60.4 to 87.3	75.3 percentage of participants Interval 58.9 to 85.9
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 Day 90	77.0 percentage of participants Interval 60.4 to 87.3	71.5 percentage of participants Interval 54.0 to 83.3

SECONDARY outcome

Timeframe: Baseline up to Day 90

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Time to Death	NA days Median and 95% confidence interval could not be calculated since an insufficient number of participants had an event.	NA days Median and 95% confidence interval could not be calculated since an insufficient number of participants had an event.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=41 Participants 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).
Time to Discharge From Intensive Care Unit (ICU)	11.1 days Interval 7.1 to 14.9	13.0 days Interval 7.2 to 16.2

SECONDARY outcome

Timeframe: Baseline up to Day 730

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Time to Discharge From Hospital	19.2 days Interval 14.4 to 30.0	18.3 days Interval 13.2 to 25.7

SECONDARY outcome

Timeframe: Baseline up to Day 730

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Length of Stay (LOS) in ICU and Hospital After Randomization Length of stay in ICU	11.1 days Interval 1.0 to 54.0	12.3 days Interval 0.0 to 121.0
Length of Stay (LOS) in ICU and Hospital After Randomization Length of stay in Hospital	19.2 days Interval 1.0 to 70.0	19.3 days Interval 1.0 to 186.0

SECONDARY outcome

Timeframe: Baseline up to Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of ICU-free Days	14.0 days Interval 0.0 to 26.0	5.5 days Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
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	8.5 Score on a scale Standard Deviation 3.01
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 3.30	-5.7 Score on a scale Standard Deviation 3.95

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
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	2 Participants
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	0 Participants
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	0 Participants
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	6 Participants
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	4 Participants
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	6 Participants
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	0 Participants
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	17 Participants
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	8 Participants
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	8 Participants
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	1 Participants
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	17 Participants
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	4 Participants
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	8 Participants
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	3 Participants
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	12 Participants
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	8 Participants
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	8 Participants
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	2 Participants
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	9 Participants
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	5 Participants
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	12 Participants
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	2 Participants
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	10 Participants
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	2 Participants
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	8 Participants
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	0 Participants
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	11 Participants
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	3 Participants
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	9 Participants
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	3 Participants
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	7 Participants
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	3 Participants
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	10 Participants
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	1 Participants
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	3 Participants
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	1 Participants
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	6 Participants
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	2 Participants
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	4 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
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	278.6 P/F ratio Standard Deviation 981.67
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 97.20	78.4 P/F ratio Standard Deviation 68.57

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion	31 Participants	37 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 29

Population: The safety population included all randomized participants who received at least one dose of the study treatment.

Any new intravenous antibiotic for CABP indication that was started after Day 1 and before Day 29 was considered a rescue antibiotic.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	Cx611 160 mL n=42 Participants 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).
Number Participants Using Rescue Antibiotics	28 Participants	32 Participants

Adverse Events

Placebo

Serious events: 20 serious events

Other events: 41 other events

Deaths: 12 deaths

Cx611 160 mL

Serious events: 24 serious events

Other events: 42 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Publication restrictions are in place

Restriction type: OTHER