Cx611-0204 SEPCELL Study

Phase 1

Completed

Conditions: Bacterial Pneumonia

Interventions: Other: Placebo
Biological: Cx611

Registration Number: NCT03158727

Lead Sponsor: Tigenix S.A.U.

Brief Summary: The purpose of this randomised, multicentre, double-blind, placebo-controlled, phase Ib/IIa study is to assess the safety, tolerability and efficacy of eASCs (Cx611) administered intravenously as adjunctive therapy, therefore in addition to standard of care (SoC) therapy, to patients with severe community-acquired bacterial pneumonia (sCABP).

The completion of this study will contribute to the basic knowledge on stem cells and their mode-of-action, and has a large translational character, i.e. to document the safety and explore the efficacy of Cx611 in patients with sCABP.

Detailed Description: The purpose of this randomised, multicentre, double-blind, placebo-controlled, phase Ib/IIa study is to assess the safety, tolerability and efficacy of eASCs (Cx611) administered intravenously as adjunctive therapy, therefore in addition to standard of care (SoC) therapy, to patients with severe community-acquired bacterial pneumonia (sCABP).

The key objectives of this study are to:

Primary objective:

Investigate the safety profile of two allogeneic Cx611 80 mL infusions administered through a central line within 3 days (on days 1 and 3) at a dose of 160 million cells each (320 million cells total) and to monitor any adverse event and potential immunological host responses against the administered cells during 90 days of follow-up after the first infusion.

Secondary objective:

Explore the clinical efficacy of Cx611 in terms of a reduction of the duration of mechanical ventilation and/or need for vasopressors and/or improved survival, and/or clinical cure of the sCABP, and other efficacy-related endpoints.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 84

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Cx611	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 90
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3	Day 3
Number of Participants With Adverse Events of Special Interest (AESI)	Baseline up to Day 90	AESIs are predefined adverse events (AEs) that required close monitoring and prompt reporting to the sponsor. Protocol-specific AEs considered as AESI for this study are thromboembolic events and hypersensitivity reactions such as anaphylaxis.
Number of Participants With Hypersensitivity Reactions	Baseline up to Day 90	Hypersensitivity reactions included anaphylaxis (changes in systolic and diastolic blood pressure, core temperature, respiratory rate \[non-ventilated participants\], heart rate), episodes of skin reactions and signs and symptoms of respiratory distress, which require therapeutic intervention including drugs and/or changes in mechanical ventilation setting. Number of participants with hypersensitivity reactions were reported for this outcome measure.
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1	Day 1
Number of Participants With Markedly Abnormal Laboratory Values	Baseline up to Day 90
Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90	At Days 1, 14, and 90

Secondary Outcome Measures

Name	Time	Method
28-day sCABP-associated Mortality	Day 28
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.
Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29	Day 29	Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Percentage of participants who were alive and free of both mechanical ventilation and vasopressors at Day 29 were reported.
Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29	Day 29
Duration of Antibiotic Treatment	Baseline up to Day 29
Number of Ventilator Free Days (VeFD)	Baseline up to Day 28	VeFD are defined as one point for each day during the measurement period that participants are both alive and free from mechanical ventilation.
Percentage of Participants Alive and Free of Vasopressors at Day 29	Day 29
Number of Vasopressor Treatment-free Days (VaFD)	Baseline up to Day 28	VaFD over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors.
Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments	Baseline up to Day 90	Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrates or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
28-day All-cause Mortality	Day 28
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.
Time to End of Vasopressors Treatment	Baseline up to Day 29	Time in days, from the start date of vasopressors treatment to the first stop date of vasopressors treatment (that is, first time the participant ends vasopressors treatment), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29	Days 8 to 10, 14, and 29	Cure:complete pneumonia resolution at baseline(BL),no new pneumonia symptoms/complications attributable.Non-response:failure related/unrelated to pneumonia:persistence/progression of BL signs/symptoms of pneumonia;BL radiographic abnormalities after atleast 2 days of treatment;development of new pulmonary/extra pulmonary findings consistent with active infection/development of new pulmonary infection/extrapulmonary infection requiring antimicrobial therapy;persistence/progression of BL signs/symptoms of severe sepsis;development of new signs/symptoms of severe sepsis;death due to sepsis.Non-response-failure unrelated to pneumonia:any cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia(e.g.myocardial infarction, pulmonary thromboembolism, sepsis of urinary origin etc).Indeterminate:extenuating circumstances precluding classification to one of the above.
Time to sCABP Clinical Cure	Baseline up to Day 29	Cure is defined as complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
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.
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.
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.
Time to Death	Baseline up to Day 90	Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time to Discharge From Intensive Care Unit (ICU)	Baseline up to Day 730	Time to discharge from ICU was defined, in days, as the time between informed consent date and the date of discharge from the ICU. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Time to Discharge From Hospital	Baseline up to Day 730	Time to discharge from hospital was defined, in days, as the time between informed consent date and the date of discharge from the hospital. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
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.
Length of Stay (LOS) in ICU and Hospital After Randomization	Baseline up to Day 730
Number of ICU-free Days	Baseline up to Day 29	ICU-free days will be defined as the number of days during which the participant was not in ICU, starting from the randomization date, to Day 29, or day of discontinuation.
Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU	Baseline up to Day 29	The total SOFA Score is a composite of six sub scores representing the degree of dysfunction of six organ systems: Respiratory, Cardiovascular, Liver, Renal, Coagulation and Central Nervous System. Each organ system sub score ranges from 0 to 4 points. The total SOFA Score is the sum of the six-organ system sub scores. Accordingly, the total SOFA Score may range from a minimum score of 0 to a maximum score of 24. Higher scores indicate greater degree of dysfunction.
Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment	Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, and 29	Number of participants with chest X-ray assessment compared to the previous assessment were assessed and reported. Number of participants which showed improvement, remission, stabilization, and worsening compared to previous CXR were reported. Cumulative data is reported only for participants who were assessed from Day 8-10.
Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)	Baseline up to Day 7
Number of Participants Requiring Mechanical Ventilation or Non-invasive Ventilation Twelve Hours After the Second Investigational Medicinal Product (IMP) Infusion	Day 3: 0 to 12 hours post-IMP infusion

Trial Locations

Locations (33): Clinique Universitaire Saint-Luc
🇧🇪
Brussels, Bruxelles, Belgium
UZ Brussel
🇧🇪
Brussels, Belgium
Clinique Saint-Pierre
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Ottignies, Belgium
CHU Bocage
🇫🇷
Dijon, France
Centre Hospitalier Departemental les Ouidairies
🇫🇷
Roche sur Yon Cedex 9, France
Centre Hospitalier Départemental les Oudairies
🇫🇷
Roche Sur Yon, France
Centre Hospitalier Universitaire de Clermont Ferrand
🇫🇷
Clermont-Ferrand, France
Centre Hospitalier Regional Universitaire de Lille
🇫🇷
Lille, France
Centre Hospitalier Universitaire de Limoges - CHU Dupuytren
🇫🇷
Limoges, France
Centre Hospitalier Universitaire de Nantes
🇫🇷
Nantes, France
Centre Hospitalier Regional d'Orleans
🇫🇷
Orléans, France
Centre Hospitalier d'Angoulême
🇫🇷
Angoulême, France
Centre Hospitalier Victor Dupouy
🇫🇷
Argenteuil, France
CHRU de Strasbourg
🇫🇷
Strasbourg, France
Klaipėda Republican Hospital, The Pulmonology and Allergology Department
🇱🇹
Klaipeda, Lithuania
Hospital Universitari Bellvitge
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
Azienda Ospedaliera San'Andrea. UOC Anestesia e Terapia Intensiva
🇮🇹
Roma, Italy
Hospital Universitario de Getafe
🇪🇸
Getafe, Madrid, Spain
Hospital Clínic I Provincial de Barcelona
🇪🇸
Barcelona, Spain
Hospital Universitari de Tarragona Joan XXIII
🇪🇸
Tarragona, Spain
Hospital Marqués de Valdecilla
🇪🇸
Santander, Spain
Hospital Virgen de la Salud
🇪🇸
Toledo, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
CHU TOURS - Hôpital Bretonneau
🇫🇷
Tours, France
St. Olavs Hospital, Department of Intensive care Clinical Immunology and Infectious Disease
🇳🇴
Trondheim, Norway
Hospital Mútua de Terrassa
🇪🇸
Terrassa, Barcelona, Spain
Hospital Universitari Arnau de Vilanova de Lleida
🇪🇸
Lleida, Spain
Hospital Universitario Ramón y Cajal
🇪🇸
Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸
Valencia, Spain
CHU Sart Tilman
🇧🇪
Liège, Belgium