Bacterial PneumoniaPhase 1/2SEPCELLNCT03158727
Cx611-0204 SEPCELL Study
A Phase 1/2 study testing Cx611 in people with Bacterial Pneumonia, run by Tigenix S.A.U. at 33 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Bacterial Pneumonia
- What is being tested?
- Cx611
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 33 sitesin 6 countries
- Study dates
- 30 Jan 2017to 7 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects of either gender (aged ≥18 years and ≤80 years old.)
- Body weight between 50 kg and 100 kg.
- 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.
- 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:
- Requiring invasive mechanical ventilation for respiratory failure due to pneumonia, or
- 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).
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- 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
- 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.
- 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:
- Subjects with Hospital acquired (HAP)-, Health Care acquired (HCAP)- or Ventilator associated-pneumonia (VAP).
- 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).
- Subjects with known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia.
- Subjects with an aspiration pneumonia.
- Subjects with known active tuberculosis.
- Subjects with a history of post-obstructive pneumonia.
- Subjects with cystic fibrosis.
- Subjects with any chronic lung disease requiring oxygen therapy at home.
- Presence of infection in another organ location caused by same pathogen (e.g. pneumococcal meningitis in the context of pneumococcal pneumonia).
- Subjects expected to have rapidly fatal disease within 72 hours after randomisation.
- Inability to maintain a mean arterial pressure ≥50 mmHg prior to screening despite the presence of vasopressors and intravenous fluids.
- Subjects not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases.
- Subjects with a history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies.
- 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.
- 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).
- 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.
- Subjects who received stem cell therapy, or allogenic transplantation (organ or bone marrow transplant) within the past 6 months.
- Subjects receiving treatment with a biological agent (e.g. antibodies, cells), immunotherapy or plasma exchange treatment within the last 8 weeks.
- 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).
- Known allergies or hypersensitivity to Penicillin or Streptomycin and/or any component of CryoStor® CS10.
- Subjects with a known liver function impairment associated with liver cirrhosis (Child Pugh C) or known oesophageal varices.
- Subjects hospitalised within the previous 15 days.
- Conditions resulting in a New York Heart Association or Canadian Cardiovascular Society Class IV functional status.
- End-stage neuromuscular disorders (e.g. motor neuron diseases, myasthenia gravis, etc.) or cerebral disorders that impair weaning.
- Patients with quadriplegia (traumatic or otherwise).
Who cannot join
None listed.
Trial locations and contacts
33 sites in 6 countries.
33 sites in 6 countries
Spain14 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clínic I Provincial de Barcelona
Barcelona, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario de Getafe
Getafe, Madrid, 28905
Hospital Universitari Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, 25198
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Marqués de Valdecilla
Santander, 39008
Hospital Universitari de Tarragona Joan XXIII
Tarragona, 43005
Hospital Mútua de Terrassa
Terrassa, Barcelona, 08221
Hospital Virgen de la Salud
Toledo
Hospital Universitario y Politécnico La Fe
Valencia, 46026
France12 sites
Centre Hospitalier d'Angoulême
Angoulême, 16959
Centre Hospitalier Victor Dupouy
Argenteuil, 95107
Centre Hospitalier Universitaire de Clermont Ferrand
Clermont-Ferrand, 63003
CHU Bocage
Dijon, 21000
Centre Hospitalier Departemental les Ouidairies
La Roche-sur-Yon, 85925
Centre Hospitalier Départemental les Oudairies
La Roche-sur-Yon, 85925
Centre Hospitalier Regional Universitaire de Lille
Lille, 59037
Centre Hospitalier Universitaire de Limoges - CHU Dupuytren
Limoges, 87000
Centre Hospitalier Universitaire de Nantes
Nantes, 44093
Centre Hospitalier Regional d'Orleans
Orléans, 45067
CHRU de Strasbourg
Strasbourg, 21000
CHU TOURS - Hôpital Bretonneau
Tours, 37000
Belgium4 sites
Clinique Universitaire Saint-Luc
Brussels, Brussels Capital, 1200
UZ Brussel
Brussels, 1090
CHU Sart Tilman
Liège, 4000
Clinique Saint-Pierre
Ottignies, 1340
Italy1 site
Azienda Ospedaliera San'Andrea. UOC Anestesia e Terapia Intensiva
Roma, 00189
Lithuania1 site
Klaipėda Republican Hospital, The Pulmonology and Allergology Department
Klaipėda, 92231
Norway1 site
St. Olavs Hospital, Department of Intensive care Clinical Immunology and Infectious Disease
Trondheim, 7030
About this study
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
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.
Read the 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.
- Conditions
- Bacterial Pneumonia
- Being tested
- Cx611, Placebo
- Keywords
- Biologic Therapy
- Medical subject headings
- Pneumonia, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cx611Biological
Two intravenous infusions, one on day 1 and another one on day 3.
PlaceboOther
Two intravenous infusions, one on day 1 and another one on day 3.
| Study group | Role | What they receive |
|---|---|---|
| Cx611 | Experimental | 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. Receives: Biological: Cx611 |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Measured: Baseline up to Day 90
Number of Participants With Adverse Events of Special Interest (AESI)
AESIs are predefined adverse events (AEs) that required close monitoring and prompt reporting to the sponsor. Protocol-specific AEs considered as AESI for this study are thromboembolic events and hypersensitivity reactions such as anaphylaxis.
Measured: Baseline up to Day 90
Number of Participants With Hypersensitivity Reactions
Hypersensitivity reactions included anaphylaxis (changes in systolic and diastolic blood pressure, core temperature, respiratory rate [non-ventilated participants], heart rate), episodes of skin reactions and signs and symptoms of respiratory distress, which require therapeutic intervention including drugs and/or changes in mechanical ventilation setting. Number of participants with hypersensitivity reactions were reported for this outcome measure.
Measured: Baseline up to Day 90
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1
Measured: Day 1
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3
Measured: Day 3
Number of Participants With Markedly Abnormal Laboratory Values
Measured: Baseline up to Day 90
Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90
Measured: At Days 1, 14, and 90
Secondary outcomes (27)
Mechanical Ventilation and Vasopressors Treatment-free Days
Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Number of days when participants were alive and free from mechanical ventilation and vasopressors were reported.
Measured: Baseline up to Day 28
Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29
Participants with sCABP suffer either a respiratory failure that requires invasive mechanical ventilation and/or a severe hypotension that requires vasopressors. Percentage of participants who were alive and free of both mechanical ventilation and vasopressors at Day 29 were reported.
Measured: Day 29
Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
Measured: Day 29
Number of Ventilator Free Days (VeFD)
VeFD are defined as one point for each day during the measurement period that participants are both alive and free from mechanical ventilation.
Measured: Baseline up to Day 28
Percentage of Participants Alive and Free of Vasopressors at Day 29
Measured: Day 29
Number of Vasopressor Treatment-free Days (VaFD)
VaFD over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors.
Measured: Baseline up to Day 28
Time to End of Invasive Mechanical Ventilation
Time in days, from the start date of invasive mechanical ventilation to the first stop date of invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 29
Time to End of Invasive and/or Non-invasive Mechanical Ventilation
Time in days, from the start date of invasive or non-invasive mechanical ventilation to the first stop date of invasive or non-invasive mechanical ventilation (that is, first time the participant ends mechanical ventilation), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 29
Time to End of Vasopressors Treatment
Time in days, from the start date of vasopressors treatment to the first stop date of vasopressors treatment (that is, first time the participant ends vasopressors treatment), or death. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 29
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29
Cure:complete pneumonia resolution at baseline(BL),no new pneumonia symptoms/complications attributable.Non-response:failure related/unrelated to pneumonia:persistence/progression of BL signs/symptoms of pneumonia;BL radiographic abnormalities after atleast 2 days of treatment;development of new pulmonary/extra pulmonary findings consistent with active infection/development of new pulmonary infection/extrapulmonary infection requiring antimicrobial therapy;persistence/progression of BL signs/symptoms of severe sepsis;development of new signs/symptoms of severe sepsis;death due to sepsis.Non-response-failure unrelated to pneumonia:any cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia(e.g.myocardial infarction, pulmonary thromboembolism, sepsis of urinary origin etc).Indeterminate:extenuating circumstances precluding classification to one of the above.
Measured: Days 8 to 10, 14, and 29
Time to sCABP Clinical Cure
Cure is defined as complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 29
Duration of Antibiotic Treatment
Measured: Baseline up to Day 29
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure
Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection.
Measured: Days 14, 29, and 90
Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments
Pneumonia recurrence is defined as a new acute clinical episode of pneumonia, after clinical cure of the episode that qualified the participant for the study, based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrates or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 90
28-day All-cause Mortality
Measured: Day 28
28-day sCABP-associated Mortality
Measured: Day 28
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Survival data for percentage of participants at Baseline and at Days 10, 20, 30, 40, 50, 60, 70, 80, and 90 was assessed and reported.
Measured: At Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Time to Death
Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 90
Time to Discharge From Intensive Care Unit (ICU)
Time to discharge from ICU was defined, in days, as the time between informed consent date and the date of discharge from the ICU. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 730
Time to Discharge From Hospital
Time to discharge from hospital was defined, in days, as the time between informed consent date and the date of discharge from the hospital. Median survival time and the associated 95% confidence interval based on Kaplan-Meier estimation are reported.
Measured: Baseline up to Day 730
Length of Stay (LOS) in ICU and Hospital After Randomization
Measured: Baseline up to Day 730
Number of ICU-free Days
ICU-free days will be defined as the number of days during which the participant was not in ICU, starting from the randomization date, to Day 29, or day of discontinuation.
Measured: Baseline up to Day 29
Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU
The total SOFA Score is a composite of six sub scores representing the degree of dysfunction of six organ systems: Respiratory, Cardiovascular, Liver, Renal, Coagulation and Central Nervous System. Each organ system sub score ranges from 0 to 4 points. The total SOFA Score is the sum of the six-organ system sub scores. Accordingly, the total SOFA Score may range from a minimum score of 0 to a maximum score of 24. Higher scores indicate greater degree of dysfunction.
Measured: Baseline up to Day 29
Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment
Number of participants with chest X-ray assessment compared to the previous assessment were assessed and reported. Number of participants which showed improvement, remission, stabilization, and worsening compared to previous CXR were reported. Cumulative data is reported only for participants who were assessed from Day 8-10.
Measured: Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, and 29
Change in the Ratio of the Partial Pressure of Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)
Measured: 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
Measured: Day 3: 0 to 12 hours post-IMP infusion
Number Participants Using Rescue Antibiotics
Any new intravenous antibiotic for CABP indication that was started after Day 1 and before Day 29 was considered a rescue antibiotic.
Measured: Baseline up to Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2017
- Study start30 Jan 2017
- Primary completion7 Jul 2020
- Study completion7 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bacterial PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tigenix S.A.U.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03158727
- Sponsor's protocol ID
- Cx611-0204
- Other IDs
- 2015-002994-39, 2015
- Acronym
- SEPCELL
- Status last verified
- Feb 2022
- First submitted
- 9 May 2017
- Last updated
- 6 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Laterre PF, Sanchez Garcia M, van der Poll T, Wittebole X, Martinez-Sagasti F, Hernandez G, Ferrer R, Caballero J, Cadogan KA, Sullivan A, Zhang B, de la Rosa O, Lombardo E, Francois B; SEPCELL Study Group. The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial. J Crit Care. 2024 Feb;79:154446. doi: 10.1016/j.jcrc.2023.154446. Epub 2023 Oct 31.
PubMed 37918129Laterre PF, Sanchez-Garcia M, van der Poll T, de la Rosa O, Cadogan KA, Lombardo E, Francois B. A phase Ib/IIa, randomised, double-blind, multicentre trial to assess the safety and efficacy of expanded Cx611 allogeneic adipose-derived stem cells (eASCs) for the treatment of patients with community-acquired bacterial pneumonia admitted to the intensive care unit. BMC Pulm Med. 2020 Nov 25;20(1):309. doi: 10.1186/s12890-020-01324-2.
PubMed 33238991
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03158727
- Acronym / sponsor ID
- SEPCELL / Cx611-0204
- Conditions
- Bacterial Pneumonia
- Keywords
- Biologic Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Tigenix S.A.U.Industry (pharma, biotech, devices)
- Collaborators
- 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
- Study start
- 30 Jan 2017 (actual)
- Primary completion
- 7 Jul 2020 (actual)
- Study completion
- 7 Jul 2020 (actual)
- First posted
- 18 May 2017 (actual)
- Results
- Posted 6 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cx611 | Experimental | Biological: Cx611Subjects 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. |
| Placebo | Placebo comparator | Other: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Adult subjects of either gender (aged ≥18 years and ≤80 years old.)
- Body weight between 50 kg and 100 kg.
- 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.
- 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:
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cx611Two intravenous infusions, one on day 1 and another one on day 3. | Biological | Cx611 |
| PlaceboTwo intravenous infusions, one on day 1 and another one on day 3. | Other | Placebo |
Primary outcome
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 90
Number of Participants With Adverse Events of Special Interest (AESI)
Time frame: 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
Time frame: 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
Time frame: Day 1
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3
Time frame: Day 3
Number of Participants With Markedly Abnormal Laboratory Values
Time frame: Baseline up to Day 90
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
27 secondary outcomes
Mechanical Ventilation and Vasopressors Treatment-free Days
Time frame: Baseline up to Day 28
Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29
Time frame: Day 29
Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
Time frame: Day 29
Number of Ventilator Free Days (VeFD)
Time frame: Baseline up to Day 28
Percentage of Participants Alive and Free of Vasopressors at Day 29
Time frame: Day 29
Number of Vasopressor Treatment-free Days (VaFD)
Time frame: Baseline up to Day 28
Time to End of Invasive Mechanical Ventilation
Time frame: Baseline up to Day 29
Time to End of Invasive and/or Non-invasive Mechanical Ventilation
Time frame: Baseline up to Day 29
Time to End of Vasopressors Treatment
Time frame: Baseline up to Day 29
Number of Participants With sCABP Clinical Response Visit at Days 8-10, 14, and 29
Time frame: Days 8 to 10, 14, and 29
Time to sCABP Clinical Cure
Time frame: Baseline up to Day 29
Duration of Antibiotic Treatment
Time frame: Baseline up to Day 29
Percentage of Participants With Pneumonia Recurrence or Reinfection After Clinical Cure
Time frame: Days 14, 29, and 90
Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments
Time frame: Baseline up to Day 90
28-day All-cause Mortality
Time frame: Day 28
28-day sCABP-associated Mortality
Time frame: Day 28
Survival at Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Time frame: At Baseline, Days 10, 20, 30, 40, 50, 60, 70, 80, and 90
Time to Death
Time frame: Baseline up to Day 90
Time to Discharge From Intensive Care Unit (ICU)
Time frame: Baseline up to Day 730
Time to Discharge From Hospital
Time frame: Baseline up to Day 730
Length of Stay (LOS) in ICU and Hospital After Randomization
Time frame: Baseline up to Day 730
Number of ICU-free Days
Time frame: Baseline up to Day 29
Change From Baseline in Sepsis-related Organ Failure Assessment (SOFA) Score During Stay at ICU
Time frame: Baseline up to Day 29
Number of Participants Categorized Based on the Chest X-ray Assessments Compared to Previous Chest X-ray Assessment
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 8-10, 14, and 29
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
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
Number Participants Using Rescue Antibiotics
Time frame: Baseline up to Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37918129Laterre PF, Sanchez Garcia M, van der Poll T, Wittebole X, Martinez-Sagasti F, Hernandez G, Ferrer R, Caballero J, Cadogan KA, Sullivan A, Zhang B, de la Rosa O, Lombardo E, Francois B; SEPCELL Study Group. The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial. J Crit Care. 2024 Feb;79:154446. doi: 10.1016/j.jcrc.2023.154446. Epub 2023 Oct 31.
- Derived from this study: PubMed 33238991Laterre PF, Sanchez-Garcia M, van der Poll T, de la Rosa O, Cadogan KA, Lombardo E, Francois B. A phase Ib/IIa, randomised, double-blind, multicentre trial to assess the safety and efficacy of expanded Cx611 allogeneic adipose-derived stem cells (eASCs) for the treatment of patients with community-acquired bacterial pneumonia admitted to the intensive care unit. BMC Pulm Med. 2020 Nov 25;20(1):309. doi: 10.1186/s12890-020-01324-2.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
33 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cx611 in people with Bacterial Pneumonia, run by Tigenix S.A.U. at 33 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Spain, France, Belgium, Italy, Lithuania and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to Day 90). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03158727, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2022.