Cx611-0204 SEPCELL Study

• Sponsor: Tigenix S.A.U. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03158727
• Collaborator: European Commission (Other), Centre Hospital Regional Universitaire de Limoges (Other), Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Hospital San Carlos, Madrid (Other)
• Enrollment: 84
• Locations: 33
• Arms: 2
• Actual Duration (Months): 41.2
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Pneumonia	Biological: Cx611; Other: Placebo	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/IIa, Randomised, Double Blind, Parallel Group, Placebo Controlled, Multicentre Study to Assess the Safety and Efficacy of Expanded Cx611 Allogeneic Adipose-derived Stem Cells (eASCs) for the Intravenous Treatment of Adult Patients With Severe Community-acquired Bacterial Pneumonia and Admitted to the Intensive Care Unit
• Actual Study Start Date: Jan 30, 2017
• Actual Primary Completion Date: Jul 7, 2020
• Actual Study Completion Date: Jul 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cx611 Subjects treated in an intensive care unit for sCABP, but that may be screened at the emergency department, will receive SoC therapy according to local guidelines plus two intravenous central line infusions of Cx611 at a fixed dose of 160 million expanded allogeneic adipose-derived stem cells (eASCs) each.	Biological: Cx611; Two intravenous infusions, one on day 1 and another one on day 3.
Placebo Comparator: Placebo Subjects treated in an intensive care unit for sCABP, but that may be screened at the emergency department, will receive SoC therapy according to local guidelines plus two intravenous central line infusions of Ringer Lactate.	Other: Placebo; Two intravenous infusions, one on day 1 and another one on day 3.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [Baseline up to Day 90]

2. 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.

3. 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.

4. Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1 [Day 1]

5. Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3 [Day 3]

6. Number of Participants With Markedly Abnormal Laboratory Values [Baseline up to Day 90]

7. 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 Outcome Measures

1. 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.

2. 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.

3. Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29 [Day 29]

4. 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.

5. Percentage of Participants Alive and Free of Vasopressors at Day 29 [Day 29]

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. Duration of Antibiotic Treatment [Baseline up to Day 29]

13. 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.

14. 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.

15. 28-day All-cause Mortality [Day 28]

16. 28-day sCABP-associated Mortality [Day 28]

17. 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.

18. Time to Death [Baseline up to Day 90]

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

19. 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.

20. 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.

21. Length of Stay (LOS) in ICU and Hospital After Randomization [Baseline up to Day 730]

22. 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.

23. 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.

24. 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.

25. Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio) [Baseline up to Day 7]

26. 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]

27. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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:

5. Requiring invasive mechanical ventilation for respiratory failure due to pneumonia, or

6. 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

1. 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.

1. 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).

1. Subjects with known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia.

2. Subjects with an aspiration pneumonia.

3. Subjects with known active tuberculosis.

4. Subjects with a history of post-obstructive pneumonia.

5. Subjects with cystic fibrosis.

6. Subjects with any chronic lung disease requiring oxygen therapy at home.

7. Presence of infection in another organ location caused by same pathogen (e.g. pneumococcal meningitis in the context of pneumococcal pneumonia).

8. Subjects expected to have rapidly fatal disease within 72 hours after randomisation.

9. Inability to maintain a mean arterial pressure ≥50 mmHg prior to screening despite the presence of vasopressors and intravenous fluids.

10. Subjects not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases.

11. Subjects with a history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies.

12. 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.

13. 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).

14. 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.

15. Subjects who received stem cell therapy, or allogenic transplantation (organ or bone marrow transplant) within the past 6 months.

16. Subjects receiving treatment with a biological agent (e.g. antibodies, cells), immunotherapy or plasma exchange treatment within the last 8 weeks.

17. 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).

18. Known allergies or hypersensitivity to Penicillin or Streptomycin and/or any component of CryoStor® CS10.

19. Subjects with a known liver function impairment associated with liver cirrhosis (Child Pugh C) or known oesophageal varices.

20. Subjects hospitalised within the previous 15 days.

21. Conditions resulting in a New York Heart Association or Canadian Cardiovascular Society Class IV functional status.

22. End-stage neuromuscular disorders (e.g. motor neuron diseases, myasthenia gravis, etc.) or cerebral disorders that impair weaning.

23. Patients with quadriplegia (traumatic or otherwise).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinique Universitaire Saint-Luc	Brussels	Bruxelles	Belgium	1200
2	UZ Brussel	Brussels		Belgium	1090
3	CHU Sart Tilman	Liège		Belgium	4000
4	Clinique Saint-Pierre	Ottignies		Belgium	1340
5	Centre Hospitalier d'Angoulême	Angoulême		France	16959
6	Centre Hospitalier Victor Dupouy	Argenteuil		France	95107
7	Centre Hospitalier Universitaire de Clermont Ferrand	Clermont-Ferrand		France	63003
8	CHU Bocage	Dijon		France	21000
9	Centre Hospitalier Regional Universitaire de Lille	Lille		France	59037
10	Centre Hospitalier Universitaire de Limoges - CHU Dupuytren	Limoges		France	87000
11	Centre Hospitalier Universitaire de Nantes	Nantes		France	44093
12	Centre Hospitalier Regional d'Orleans	Orléans		France	45067
13	Centre Hospitalier Departemental les Ouidairies	Roche sur Yon Cedex 9		France	85925
14	Centre Hospitalier Départemental les Oudairies	Roche Sur Yon		France	85925
15	CHRU de Strasbourg	Strasbourg		France	21000
16	CHU TOURS - Hôpital Bretonneau	Tours		France	37000
17	Azienda Ospedaliera San'Andrea. UOC Anestesia e Terapia Intensiva	Roma		Italy	00189
18	Klaipėda Republican Hospital, The Pulmonology and Allergology Department	Klaipeda		Lithuania	92231
19	St. Olavs Hospital, Department of Intensive care Clinical Immunology and Infectious Disease	Trondheim		Norway	7030
20	Hospital Universitari Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
21	Hospital Mútua de Terrassa	Terrassa	Barcelona	Spain	08221
22	Hospital Universitario de Getafe	Getafe	Madrid	Spain	28905
23	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
24	Hospital Clínic I Provincial de Barcelona	Barcelona		Spain	08036
25	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
26	Hospital Universitari Arnau de Vilanova de Lleida	Lleida		Spain	25198
27	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
28	Hospital Clínico San Carlos	Madrid		Spain	28040
29	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
30	Hospital Marqués de Valdecilla	Santander		Spain	39008
31	Hospital Universitari de Tarragona Joan XXIII	Tarragona		Spain	43005
32	Hospital Virgen de la Salud	Toledo		Spain
33	Hospital Universitario y Politécnico La Fe	Valencia		Spain	46026

Sponsors and Collaborators

• Tigenix S.A.U.
• 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

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2019
• Statistical Analysis Plan - Mar 4, 2020

More Information

Publications

None provided.

• Responsible Party: Tigenix S.A.U.
• ClinicalTrials.gov Identifier: NCT03158727
• Other Study ID Numbers: Cx611-0204; 2015-002994-39
• First Posted: May 18, 2017
• Last Update Posted: Apr 6, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tigenix S.A.U.: Biologic Therapy
• Additional relevant MeSH terms: Pneumonia; Pneumonia, Bacterial

Study Results

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 Detail	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.

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Period Title: Overall Study
STARTED	42	42
Enrolled, Not Treated	1	0
COMPLETED	25	23
NOT COMPLETED	17	19

Baseline Characteristics

Arm/Group Title	Placebo	Cx611 160 mL	Total
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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 of all reporting groups
Overall Participants	41	42	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (10.43)	61.1 (11.24)	62.3 (10.84)
Sex: Female, Male (Count of Participants)
Female	15 36.6%	14 33.3%	29 34.9%
Male	26 63.4%	28 66.7%	54 65.1%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	31 75.6%	28 66.7%	59 71.1%
Asian/Oriental	1 2.4%	0 0%	1 1.2%
Hispanic	1 2.4%	1 2.4%	2 2.4%
Latino	2 4.9%	1 2.4%	3 3.6%
Unknown	6 14.6%	12 28.6%	18 21.7%
Region of Enrollment (Count of Participants)
Belgium	12 29.3%	7 16.7%	19 22.9%
Spain	23 56.1%	22 52.4%	45 54.2%
Lithuania	0 0%	1 2.4%	1 1.2%
France	6 14.6%	12 28.6%	18 21.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time Frame	Baseline up to Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	37 90.2%	40 95.2%

2. Primary Outcome

Title	Number of Participants With Adverse Events of Special Interest (AESI)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	9 22%	7 16.7%

3. Primary Outcome

Title	Number of Participants With Hypersensitivity Reactions
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	1 2.4%	0 0%

4. Primary Outcome

Title	Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	3 7.3%	7 16.7%

5. Primary Outcome

Title	Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	5 12.2%	4 9.5%

6. Primary Outcome

Title	Number of Participants With Markedly Abnormal Laboratory Values
Time Frame	Baseline up to Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	0 0%	0 0%

7. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Participants with Anti-HLA/Donor Antibodies at Day 1	6 14.6%	4 9.5%
Participants with Anti-HLA/Donor Antibodies at Day 14	4 9.8%	5 11.9%
Participants with Anti-HLA/Donor Antibodies at Day 90	4 9.8%	4 9.5%

8. Secondary Outcome

Title	Mechanical Ventilation and Vasopressors Treatment-free Days
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (Full Range) [days]	19.0	13.5

9. Secondary Outcome

Title	Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Number [percentage of participants]	78.0 190.2%	64.3 153.1%

10. Secondary Outcome

Title	Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Number [percentage of participants]	78.0 190.2%	66.7 158.8%

11. Secondary Outcome

Title	Number of Ventilator Free Days (VeFD)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (Full Range) [days]	19.0	14.0

12. Secondary Outcome

Title	Percentage of Participants Alive and Free of Vasopressors at Day 29
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Number [percentage of participants]	85.4 208.3%	76.2 181.4%

13. Secondary Outcome

Title	Number of Vasopressor Treatment-free Days (VaFD)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (Full Range) [days]	24.0	23.5

14. Secondary Outcome

Title	Time to End of Invasive Mechanical Ventilation
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	33	39
Median (95% Confidence Interval) [days]	7.7	8.3

15. Secondary Outcome

Title	Time to End of Invasive and/or Non-invasive Mechanical Ventilation
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	33	39
Median (95% Confidence Interval) [days]	6.3	4.7

16. Secondary Outcome

Title	Time to End of Vasopressors Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	33	34
Median (95% Confidence Interval) [days]	2.1	2.0

17. Secondary Outcome

Title	Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Days 8 to 10 (Cure)	18 43.9%	21 50%
Days 8 to 10 (Failure not resulting in death)	8 19.5%	6 14.3%
Days 8 to 10 (Indeterminate)	11 26.8%	9 21.4%
Days 8 to 10 (Missing)	1 2.4%	0 0%
Day 14 (Cure)	24 58.5%	24 57.1%
Day 14 (Failure not resulting in death)	5 12.2%	4 9.5%
Day 14 (Indeterminate)	6 14.6%	4 9.5%
Day 14 (Missing)	1 2.4%	1 2.4%
Day 29 (Cure)	30 73.2%	26 61.9%
Day 29 (Failure not resulting in death)	1 2.4%	1 2.4%
Day 29 (Indeterminate)	0 0%	3 7.1%
Day 29 (Missing)	1 2.4%	0 0%

18. Secondary Outcome

Title	Time to sCABP Clinical Cure
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (95% Confidence Interval) [days]	13.0	9.5

19. Secondary Outcome

Title	Duration of Antibiotic Treatment
Time Frame	Baseline up to Day 29

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	39	38
Median (Full Range) [days]	9.0	8.0

20. Secondary Outcome

Title	Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	36	33
Day 14: Recurrence	5.6 13.7%	0 0%
Day 14: Reinfection	8.3 20.2%	6.1 14.5%
Day 29: Recurrence	0 0%	3.3 7.9%
Day 29: Reinfection	0 0%	0 0%
Day 90: Recurrence	0 0%	0 0%
Day 90: Reinfection	0 0%	0 0%

21. Secondary Outcome

Title	Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	34	32
Median (95% Confidence Interval) [days]	NA	NA

22. Secondary Outcome

Title	28-day All-cause Mortality
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	6 14.6%	8 19%

23. Secondary Outcome

Title	28-day sCABP-associated Mortality
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	0 0%	1 2.4%

24. Secondary Outcome

Title	Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Baseline	100.0 243.9%	100.0 238.1%
Day 10	95.1 232%	88.1 209.8%
Day 20	87.5 213.4%	80.7 192.1%
Day 30	85.0 207.3%	80.7 192.1%
Day 40	77.0 187.8%	80.7 192.1%
Day 50	77.0 187.8%	75.3 179.3%
Day 60	77.0 187.8%	75.3 179.3%
Day 70	77.0 187.8%	75.3 179.3%
Day 80	77.0 187.8%	75.3 179.3%
Day 90	77.0 187.8%	71.5 170.2%

25. Secondary Outcome

Title	Time to Death
Description	Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time Frame	Baseline up to Day 90

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (95% Confidence Interval) [days]	NA	NA

26. Secondary Outcome

Title	Time to Discharge From Intensive Care Unit (ICU)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	41
Median (95% Confidence Interval) [days]	11.1	13.0

27. Secondary Outcome

Title	Time to Discharge From Hospital
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (95% Confidence Interval) [days]	19.2	18.3

28. Secondary Outcome

Title	Length of Stay (LOS) in ICU and Hospital After Randomization
Time Frame	Baseline up to Day 730

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Length of stay in ICU	11.1	12.3
Length of stay in Hospital	19.2	19.3

29. Secondary Outcome

Title	Number of ICU-free Days
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Median (Full Range) [days]	14.0	5.5

30. Secondary Outcome

Title	Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	40	42
Baseline	7.9 (2.39)	8.5 (3.01)
Change at Day 29	-6.1 (3.30)	-5.7 (3.95)

31. Secondary Outcome

Title	Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Improvement at Day 1: Compared to previous chest X-ray	0 0%	0 0%
Remission at Day 1: Compared to previous chest X-ray	0 0%	0 0%
Stabilization at Day 1: Compared to previous chest X-ray	7 17.1%	6 14.3%
Worsening at Day 1: Compared to previous chest X-ray	2 4.9%	4 9.5%
Improvement at Day 2: Compared to previous chest X-ray	9 22%	6 14.3%
Remission at Day 2: Compared to previous chest X-ray	0 0%	0 0%
Stabilization at Day 2: Compared to previous chest X-ray	17 41.5%	17 40.5%
Worsening at Day 2: Compared to previous chest X-ray	8 19.5%	8 19%
Improvement at Day 3: Compared to previous chest X-ray	19 46.3%	8 19%
Remission at Day 3: Compared to previous chest X-ray	0 0%	1 2.4%
Stabilization at Day 3: Compared to previous chest X-ray	17 41.5%	17 40.5%
Worsening at Day 3: Compared to previous chest X-ray	1 2.4%	4 9.5%
Improvement at Day 4: Compared to previous chest X-ray	14 34.1%	8 19%
Remission at Day 4: Compared to previous chest X-ray	1 2.4%	3 7.1%
Stabilization at Day 4: Compared to previous chest X-ray	15 36.6%	12 28.6%
Worsening at Day 4: Compared to previous chest X-ray	0 0%	8 19%
Improvement at Day 5: Compared to previous chest X-ray	5 12.2%	8 19%
Remission at Day 5: Compared to previous chest X-ray	2 4.9%	2 4.8%
Stabilization at Day 5: Compared to previous chest X-ray	7 17.1%	9 21.4%
Worsening at Day 5: Compared to previous chest X-ray	6 14.6%	5 11.9%
Improvement at Day 6: Compared to previous chest X-ray	11 26.8%	12 28.6%
Remission at Day 6: Compared to previous chest X-ray	1 2.4%	2 4.8%
Stabilization at Day 6: Compared to previous chest X-ray	15 36.6%	10 23.8%
Worsening at Day 6: Compared to previous chest X-ray	2 4.9%	2 4.8%
Improvement at Day 7: Compared to previous chest X-ray	8 19.5%	8 19%
Remission at Day 7: Compared to previous chest X-ray	0 0%	0 0%
Stabilization at Day 7: Compared to previous chest X-ray	7 17.1%	11 26.2%
Worsening at Day 7: Compared to previous chest X-ray	3 7.3%	3 7.1%
Improvement at Days 8-10: Compared to previous chest X-ray	8 19.5%	9 21.4%
Remission at Days 8-10: Compared to previous chest X-ray	3 7.3%	3 7.1%
Stabilization at Days 8-10: Compared to previous chest X-ray	11 26.8%	7 16.7%
Worsening at Days 8-10: Compared to previous chest X-ray	5 12.2%	3 7.1%
Improvement at Day 14: Compared to previous chest X-ray	10 24.4%	10 23.8%
Remission at Day 14: Compared to previous chest X-ray	1 2.4%	1 2.4%
Stabilization at Day 14: Compared to previous chest X-ray	5 12.2%	3 7.1%
Worsening at Day 14: Compared to previous chest X-ray	5 12.2%	1 2.4%
Improvement at Day 29: Compared to previous chest X-ray	3 7.3%	6 14.3%
Remission at Day 29: Compared to previous chest X-ray	3 7.3%	2 4.8%
Stabilization at Day 29: Compared to previous chest X-ray	2 4.9%	4 9.5%
Worsening at Day 29: Compared to previous chest X-ray	1 2.4%	2 4.8%

32. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Baseline	131.6 (55.14)	278.6 (981.67)
Change at Day 7	74.6 (97.20)	78.4 (68.57)

33. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	31 75.6%	37 88.1%

34. Secondary Outcome

Title	Number Participants Using Rescue Antibiotics
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.	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).
Measure Participants	41	42
Count of Participants [Participants]	28 68.3%	32 76.2%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started from the signature of the informed consent (Baseline) up to Day 730
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Placebo		Cx611 160 mL
Arm/Group Description	Participants received SoC therapy followed by two 80 mL central line infusions of placebo, intravenously, on Days 1 and 3.		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).
All Cause Mortality
	Placebo		Cx611 160 mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/41 (29.3%)		13/42 (31%)
Serious Adverse Events
	Placebo		Cx611 160 mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/41 (48.8%)		24/42 (57.1%)
Blood and lymphatic system disorders
Haemolysis	0/41 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
Atrial fibrillation	1/41 (2.4%)	1	0/42 (0%)	0
Atrial thrombosis	0/41 (0%)	0	1/42 (2.4%)	1
Atrioventricular block complete	2/41 (4.9%)	2	0/42 (0%)	0
Atrioventricular dissociation	0/41 (0%)	0	1/42 (2.4%)	1
Cardiac arrest	1/41 (2.4%)	1	2/42 (4.8%)	2
Cardiac failure congestive	1/41 (2.4%)	1	0/42 (0%)	0
Cardio-respiratory arrest	1/41 (2.4%)	1	0/42 (0%)	0
Cardiogenic shock	0/41 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Gastric ulcer	1/41 (2.4%)	1	0/42 (0%)	0
Ileus paralytic	1/41 (2.4%)	1	0/42 (0%)	0
Intestinal ischaemia	0/41 (0%)	0	1/42 (2.4%)	1
Subileus	0/41 (0%)	0	1/42 (2.4%)	1
General disorders
Fibrosis	0/41 (0%)	0	1/42 (2.4%)	1
Multiple organ dysfunction syndrome	4/41 (9.8%)	4	1/42 (2.4%)	1
Hepatobiliary disorders
Acute hepatic failure	1/41 (2.4%)	1	0/42 (0%)	0
Hepatic failure	0/41 (0%)	0	1/42 (2.4%)	1
Ischaemic hepatitis	0/41 (0%)	0	1/42 (2.4%)	1
Immune system disorders
Anaphylactic shock	1/41 (2.4%)	1	0/42 (0%)	0
Infections and infestations
Bronchopulmonary aspergillosis	1/41 (2.4%)	1	0/42 (0%)	0
Enterococcal bacteraemia	1/41 (2.4%)	1	0/42 (0%)	0
Pneumonia	0/41 (0%)	0	2/42 (4.8%)	2
Pneumonia klebsiella	0/41 (0%)	0	1/42 (2.4%)	1
Prostate infection	0/41 (0%)	0	1/42 (2.4%)	1
Septic shock	0/41 (0%)	0	2/42 (4.8%)	2
Toxic shock syndrome	0/41 (0%)	0	1/42 (2.4%)	1
Tracheobronchitis	0/41 (0%)	0	1/42 (2.4%)	1
Urosepsis	1/41 (2.4%)	1	0/42 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	0/41 (0%)	0	1/42 (2.4%)	1
Investigations
Alanine aminotransferase increased	0/41 (0%)	0	1/42 (2.4%)	1
Aspartate aminotransferase increased	0/41 (0%)	0	1/42 (2.4%)	1
Aspiration bronchial	1/41 (2.4%)	1	0/42 (0%)	0
Blood lactate dehydrogenase increased	0/41 (0%)	0	1/42 (2.4%)	1
Metabolism and nutrition disorders
Gout	1/41 (2.4%)	1	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/41 (2.4%)	1	0/42 (0%)	0
Nervous system disorders
Cerebral artery embolism	0/41 (0%)	0	1/42 (2.4%)	1
Cerebral haemorrhage	0/41 (0%)	0	1/42 (2.4%)	1
Cerebrovascular accident	0/41 (0%)	0	1/42 (2.4%)	1
Intensive care unit acquired weakness	0/41 (0%)	0	1/42 (2.4%)	1
Renal and urinary disorders
Acute kidney injury	0/41 (0%)	0	3/42 (7.1%)	3
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/41 (0%)	0	1/42 (2.4%)	1
Acute respiratory distress syndrome	1/41 (2.4%)	1	1/42 (2.4%)	1
Hypercapnia	1/41 (2.4%)	1	0/42 (0%)	0
Hypoxia	2/41 (4.9%)	2	2/42 (4.8%)	2
Obstructive airways disorder	0/41 (0%)	0	1/42 (2.4%)	1
Pulmonary embolism	1/41 (2.4%)	1	1/42 (2.4%)	1
Respiratory acidosis	1/41 (2.4%)	1	0/42 (0%)	0
Respiratory distress	0/41 (0%)	0	1/42 (2.4%)	1
Respiratory failure	3/41 (7.3%)	3	1/42 (2.4%)	1
Skin and subcutaneous tissue disorders
Urticaria	1/41 (2.4%)	1	0/42 (0%)	0
Surgical and medical procedures
Coronary artery bypass	1/41 (2.4%)	1	0/42 (0%)	0
Mitral valve replacement	1/41 (2.4%)	1	0/42 (0%)	0
Vascular disorders
Arterial thrombosis	0/41 (0%)	0	1/42 (2.4%)	1
Deep vein thrombosis	0/41 (0%)	0	2/42 (4.8%)	2
Jugular vein thrombosis	1/41 (2.4%)	1	0/42 (0%)	0
Peripheral ischaemia	1/41 (2.4%)	1	0/42 (0%)	0
Shock	0/41 (0%)	0	1/42 (2.4%)	1
Venous thrombosis limb	1/41 (2.4%)	1	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Cx611 160 mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/41 (100%)		42/42 (100%)
Blood and lymphatic system disorders
Anaemia	9/41 (22%)	9	8/42 (19%)	8
Anaemia macrocytic	0/41 (0%)	0	1/42 (2.4%)	1
Coagulopathy	1/41 (2.4%)	1	0/42 (0%)	0
Heparin-induced thrombocytopenia	1/41 (2.4%)	1	0/42 (0%)	0
Leukocytosis	0/41 (0%)	0	1/42 (2.4%)	1
Lymphopenia	0/41 (0%)	0	1/42 (2.4%)	1
Normochromic normocytic anaemia	1/41 (2.4%)	1	0/42 (0%)	0
Thrombocytopenia	1/41 (2.4%)	1	3/42 (7.1%)	3
Thrombocytosis	2/41 (4.9%)	2	1/42 (2.4%)	1
Thymus disorder	0/41 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
Arrhythmia	1/41 (2.4%)	1	0/42 (0%)	0
Atrial fibrillation	3/41 (7.3%)	3	6/42 (14.3%)	6
Bradycardia	2/41 (4.9%)	2	0/42 (0%)	0
Bundle branch block left	0/41 (0%)	0	2/42 (4.8%)	2
Cardiac failure	1/41 (2.4%)	1	0/42 (0%)	0
Extrasystoles	1/41 (2.4%)	1	0/42 (0%)	0
Mitral valve incompetence	0/41 (0%)	0	1/42 (2.4%)	1
Pericardial effusion	1/41 (2.4%)	1	0/42 (0%)	0
Sinus tachycardia	0/41 (0%)	0	1/42 (2.4%)	1
Supraventricular extrasystoles	0/41 (0%)	0	1/42 (2.4%)	1
Supraventricular tachycardia	0/41 (0%)	0	1/42 (2.4%)	1
Tachycardia	1/41 (2.4%)	1	2/42 (4.8%)	2
Endocrine disorders
Adrenal insufficiency	0/41 (0%)	0	1/42 (2.4%)	1
Hyperparathyroidism	1/41 (2.4%)	1	0/42 (0%)	0
Primary hypothyroidism	0/41 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Abdominal distension	0/41 (0%)	0	4/42 (9.5%)	4
Ascites	0/41 (0%)	0	1/42 (2.4%)	1
Colitis	1/41 (2.4%)	1	0/42 (0%)	0
Colonic pseudo-obstruction	1/41 (2.4%)	1	0/42 (0%)	0
Constipation	4/41 (9.8%)	4	5/42 (11.9%)	5
Diarrhoea	4/41 (9.8%)	4	5/42 (11.9%)	5
Gastrointestinal haemorrhage	0/41 (0%)	0	1/42 (2.4%)	1
Haematemesis	0/41 (0%)	0	1/42 (2.4%)	1
Impaired gastric emptying	0/41 (0%)	0	1/42 (2.4%)	1
Loose tooth	1/41 (2.4%)	1	0/42 (0%)	0
Mouth haemorrhage	0/41 (0%)	0	1/42 (2.4%)	1
Nausea	0/41 (0%)	0	1/42 (2.4%)	1
Odynophagia	0/41 (0%)	0	1/42 (2.4%)	1
Oesophagitis	0/41 (0%)	0	1/42 (2.4%)	1
Pancreatitis acute	0/41 (0%)	0	1/42 (2.4%)	1
Rectal haemorrhage	0/41 (0%)	0	1/42 (2.4%)	1
Tooth loss	1/41 (2.4%)	1	0/42 (0%)	0
Toothache	0/41 (0%)	0	1/42 (2.4%)	1
Vomiting	0/41 (0%)	0	5/42 (11.9%)	5
General disorders
Asthenia	0/41 (0%)	0	1/42 (2.4%)	1
Device related thrombosis	0/41 (0%)	0	1/42 (2.4%)	1
Generalised oedema	1/41 (2.4%)	1	0/42 (0%)	0
Hyperthermia	0/41 (0%)	0	1/42 (2.4%)	1
Hypothermia	2/41 (4.9%)	2	0/42 (0%)	0
Malaise	0/41 (0%)	0	1/42 (2.4%)	1
Oedema	1/41 (2.4%)	1	0/42 (0%)	0
Oedema peripheral	1/41 (2.4%)	1	3/42 (7.1%)	3
Puncture site haemorrhage	1/41 (2.4%)	1	0/42 (0%)	0
Pyrexia	1/41 (2.4%)	1	2/42 (4.8%)	2
Hepatobiliary disorders
Cholestasis	1/41 (2.4%)	1	5/42 (11.9%)	5
Hepatic cirrhosis	0/41 (0%)	0	1/42 (2.4%)	1
Hepatic failure	0/41 (0%)	0	1/42 (2.4%)	1
Hepatocellular injury	2/41 (4.9%)	2	0/42 (0%)	0
Hepatomegaly	1/41 (2.4%)	1	0/42 (0%)	0
Hepatorenal syndrome	0/41 (0%)	0	1/42 (2.4%)	1
Hypertransaminasaemia	1/41 (2.4%)	1	0/42 (0%)	0
Infections and infestations
Citrobacter infection	0/41 (0%)	0	1/42 (2.4%)	1
Conjunctivitis	1/41 (2.4%)	1	0/42 (0%)	0
Empyema	2/41 (4.9%)	2	1/42 (2.4%)	1
Fungal skin infection	1/41 (2.4%)	1	0/42 (0%)	0
Genital candidiasis	1/41 (2.4%)	1	0/42 (0%)	0
Herpes virus infection	1/41 (2.4%)	1	0/42 (0%)	0
Infectious pleural effusion	0/41 (0%)	0	1/42 (2.4%)	1
Influenza	1/41 (2.4%)	1	0/42 (0%)	0
Mediastinitis	0/41 (0%)	0	1/42 (2.4%)	1
Nasopharyngitis	0/41 (0%)	0	1/42 (2.4%)	1
Oral herpes	0/41 (0%)	0	1/42 (2.4%)	1
Pneumonia	0/41 (0%)	0	1/42 (2.4%)	1
Pseudomonal sepsis	0/41 (0%)	0	1/42 (2.4%)	1
Pseudomonas infection	2/41 (4.9%)	2	0/42 (0%)	0
Rhinitis	1/41 (2.4%)	1	0/42 (0%)	0
Sepsis	1/41 (2.4%)	1	0/42 (0%)	0
Septic shock	1/41 (2.4%)	1	0/42 (0%)	0
Serratia infection	0/41 (0%)	0	1/42 (2.4%)	1
Skin candida	1/41 (2.4%)	1	0/42 (0%)	0
Subcutaneous abscess	0/41 (0%)	0	1/42 (2.4%)	1
Tracheitis	0/41 (0%)	0	1/42 (2.4%)	1
Urinary tract infection	0/41 (0%)	0	2/42 (4.8%)	2
Urinary tract infection pseudomonal	0/41 (0%)	0	1/42 (2.4%)	1
Injury, poisoning and procedural complications
Axillary nerve injury	0/41 (0%)	0	1/42 (2.4%)	1
Endotracheal intubation complication	0/41 (0%)	0	1/42 (2.4%)	1
Eschar	2/41 (4.9%)	2	0/42 (0%)	0
Fall	0/41 (0%)	0	2/42 (4.8%)	2
Toxicity to various agents	1/41 (2.4%)	1	0/42 (0%)	0
Tracheal haemorrhage	1/41 (2.4%)	1	0/42 (0%)	0
Investigations
Alanine aminotransferase increased	1/41 (2.4%)	1	0/42 (0%)	0
Aspartate aminotransferase increased	1/41 (2.4%)	1	0/42 (0%)	0
Blood alkaline phosphatase increased	1/41 (2.4%)	1	0/42 (0%)	0
Blood creatine phosphokinase increased	1/41 (2.4%)	1	0/42 (0%)	0
Blood lactate dehydrogenase increased	1/41 (2.4%)	1	0/42 (0%)	0
Electrocardiogram QT prolonged	1/41 (2.4%)	1	0/42 (0%)	0
Gamma-glutamyltransferase increased	1/41 (2.4%)	1	0/42 (0%)	0
Staphylococcus test positive	0/41 (0%)	0	1/42 (2.4%)	1
Transaminases increased	1/41 (2.4%)	1	0/42 (0%)	0
Weight decreased	1/41 (2.4%)	1	0/42 (0%)	0
Metabolism and nutrition disorders
Cell death	0/41 (0%)	0	1/42 (2.4%)	1
Feeding intolerance	0/41 (0%)	0	1/42 (2.4%)	1
Hyperammonaemia	0/41 (0%)	0	1/42 (2.4%)	1
Hyperamylasaemia	0/41 (0%)	0	1/42 (2.4%)	1
Hypercholesterolaemia	1/41 (2.4%)	1	1/42 (2.4%)	1
Hyperglycaemia	1/41 (2.4%)	1	4/42 (9.5%)	4
Hyperkalaemia	4/41 (9.8%)	4	2/42 (4.8%)	2
Hyperlactacidaemia	0/41 (0%)	0	1/42 (2.4%)	1
Hypernatraemia	6/41 (14.6%)	6	1/42 (2.4%)	1
Hyperphosphataemia	1/41 (2.4%)	1	0/42 (0%)	0
Hypervolaemia	1/41 (2.4%)	1	0/42 (0%)	0
Hypoalbuminaemia	1/41 (2.4%)	1	1/42 (2.4%)	1
Hypocalcaemia	0/41 (0%)	0	1/42 (2.4%)	1
Hypoglycaemia	0/41 (0%)	0	3/42 (7.1%)	3
Hypokalaemia	4/41 (9.8%)	4	5/42 (11.9%)	5
Hypomagnesaemia	0/41 (0%)	0	1/42 (2.4%)	1
Hyponatraemia	0/41 (0%)	0	3/42 (7.1%)	3
Hypophosphataemia	3/41 (7.3%)	3	2/42 (4.8%)	2
Malnutrition	0/41 (0%)	0	1/42 (2.4%)	1
Metabolic acidosis	1/41 (2.4%)	1	0/42 (0%)	0
Metabolic alkalosis	1/41 (2.4%)	1	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/41 (0%)	0	1/42 (2.4%)	1
Back pain	0/41 (0%)	0	1/42 (2.4%)	1
Muscular weakness	0/41 (0%)	0	1/42 (2.4%)	1
Myopathy	1/41 (2.4%)	1	2/42 (4.8%)	2
Nervous system disorders
Agitation	1/41 (2.4%)	1	0/42 (0%)	0
Akinesia	0/41 (0%)	0	1/42 (2.4%)	1
Cerebrovascular accident	0/41 (0%)	0	1/42 (2.4%)	1
Essential tremor	0/41 (0%)	0	1/42 (2.4%)	1
Facial paralysis	0/41 (0%)	0	1/42 (2.4%)	1
Hepatic encephalopathy	1/41 (2.4%)	1	0/42 (0%)	0
Intensive care unit acquired weakness	0/41 (0%)	0	1/42 (2.4%)	1
Memory impairment	0/41 (0%)	0	1/42 (2.4%)	1
Paraparesis	1/41 (2.4%)	1	0/42 (0%)	0
Partial seizures	0/41 (0%)	0	1/42 (2.4%)	1
Partial seizures with secondary generalisation	0/41 (0%)	0	1/42 (2.4%)	1
Presyncope	0/41 (0%)	0	1/42 (2.4%)	1
Tremor	0/41 (0%)	0	1/42 (2.4%)	1
Psychiatric disorders
Agitation	2/41 (4.9%)	2	4/42 (9.5%)	4
Aggression	0/41 (0%)	0	1/42 (2.4%)	1
Anxiety	0/41 (0%)	0	4/42 (9.5%)	4
Confusional state	1/41 (2.4%)	1	1/42 (2.4%)	1
Delirium	1/41 (2.4%)	1	0/42 (0%)	0
Depression	0/41 (0%)	0	1/42 (2.4%)	1
Hallucination, visual	0/41 (0%)	0	1/42 (2.4%)	1
Insomnia	1/41 (2.4%)	1	1/42 (2.4%)	1
Renal and urinary disorders
Acute kidney injury	2/41 (4.9%)	2	1/42 (2.4%)	1
Chronic kidney disease	1/41 (2.4%)	1	0/42 (0%)	0
Dysuria	0/41 (0%)	0	1/42 (2.4%)	1
Haematuria	0/41 (0%)	0	1/42 (2.4%)	1
Neurogenic bladder	1/41 (2.4%)	1	0/42 (0%)	0
Oliguria	0/41 (0%)	0	1/42 (2.4%)	1
Renal failure	1/41 (2.4%)	1	0/42 (0%)	0
Renal impairment	0/41 (0%)	0	2/42 (4.8%)	2
Reproductive system and breast disorders
Penile oedema	0/41 (0%)	0	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/41 (0%)	0	1/42 (2.4%)	1
Acute respiratory distress syndrome	0/41 (0%)	0	1/42 (2.4%)	1
Atelectasis	2/41 (4.9%)	2	3/42 (7.1%)	3
Bronchospasm	1/41 (2.4%)	1	1/42 (2.4%)	1
Chronic obstructive pulmonary disease	1/41 (2.4%)	1	1/42 (2.4%)	1
Cough	1/41 (2.4%)	1	0/42 (0%)	0
Epistaxis	1/41 (2.4%)	1	0/42 (0%)	0
Haemothorax	1/41 (2.4%)	1	0/42 (0%)	0
Hypercapnia	1/41 (2.4%)	1	0/42 (0%)	0
Hypoxia	1/41 (2.4%)	1	1/42 (2.4%)	1
Pharyngeal haemorrhage	0/41 (0%)	0	1/42 (2.4%)	1
Pleural effusion	1/41 (2.4%)	1	1/42 (2.4%)	1
Pleuritic pain	1/41 (2.4%)	1	0/42 (0%)	0
Pneumothorax	1/41 (2.4%)	1	1/42 (2.4%)	1
Pulmonary embolism	1/41 (2.4%)	1	0/42 (0%)	0
Pulmonary fibrosis	1/41 (2.4%)	1	0/42 (0%)	0
Pulmonary oedema	1/41 (2.4%)	1	0/42 (0%)	0
Respiratory acidosis	1/41 (2.4%)	1	1/42 (2.4%)	1
Respiratory disorder	0/41 (0%)	0	1/42 (2.4%)	1
Respiratory distress	0/41 (0%)	0	1/42 (2.4%)	1
Sleep apnoea syndrome	1/41 (2.4%)	1	0/42 (0%)	0
Stridor	0/41 (0%)	0	1/42 (2.4%)	1
Skin and subcutaneous tissue disorders
Acne	1/41 (2.4%)	1	0/42 (0%)	0
Alopecia	0/41 (0%)	0	1/42 (2.4%)	1
Decubitus ulcer	2/41 (4.9%)	2	2/42 (4.8%)	2
Erythema	1/41 (2.4%)	1	3/42 (7.1%)	3
Intertrigo	0/41 (0%)	0	1/42 (2.4%)	1
Rash	1/41 (2.4%)	1	2/42 (4.8%)	2
Rash macular	1/41 (2.4%)	1	0/42 (0%)	0
Skin lesion	1/41 (2.4%)	1	0/42 (0%)	0
Skin maceration	0/41 (0%)	0	1/42 (2.4%)	1
Skin reaction	1/41 (2.4%)	1	0/42 (0%)	0
Skin ulcer	0/41 (0%)	0	1/42 (2.4%)	1
Subcutaneous emphysema	1/41 (2.4%)	1	0/42 (0%)	0
Urticaria	0/41 (0%)	0	1/42 (2.4%)	1
Vascular disorders
Deep vein thrombosis	5/41 (12.2%)	5	1/42 (2.4%)	1
Hypertension	2/41 (4.9%)	2	6/42 (14.3%)	6
Hypotension	1/41 (2.4%)	1	2/42 (4.8%)	2
Ischaemia	1/41 (2.4%)	1	1/42 (2.4%)	1
Phlebitis	1/41 (2.4%)	1	1/42 (2.4%)	1
Venous thrombosis	1/41 (2.4%)	1	0/42 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.