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Cx611-0204 SEPCELL Study (SEPCELL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03158727
Recruitment Status : Active, not recruiting
First Posted : May 18, 2017
Last Update Posted : July 28, 2020
Sponsor:
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
Information provided by (Responsible Party):
Takeda ( Tigenix S.A.U. )

Tracking Information
First Submitted Date  ICMJE May 9, 2017
First Posted Date  ICMJE May 18, 2017
Last Update Posted Date July 28, 2020
Actual Study Start Date  ICMJE January 30, 2017
Actual Primary Completion Date July 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
  • Number of Participants Reporting one or More Adverse Event (AE) [ 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 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 Categorized Based on Hypersensitivity Reactions [ Time Frame: Baseline up to Day 90 ]
    Hypersensitivity reactions may include 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 Markedly Abnormal Values of Vital Signs Parameters [ Time Frame: Baseline up to Day 90 ]
  • Number of Participants With Markedly Abnormal Values of Electrocardiogram (ECG) Parameters [ Time Frame: Baseline up to Day 90 ]
  • 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 [ Time Frame: Baseline up to Day 90 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
Safety profile of 2 allogeneic Cx611 central line infusions at a dose of 160 million cells each [ Time Frame: 90 days ]
Investigate the safety profile of 2 allogeneic Cx611 central line infusions within 3 days, at a dose of 160 million cells each and to monitor any adverse event and potential immunological host responses against the administered cells during 90 days of follow-up.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
  • Number of Days That Participants are Alive and Free from Mechanical Ventilation and Vasopressors [ Time Frame: Baseline up to Day 29 ]
  • Percentage of Participants Alive and Free of 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 (VFD) [ Time Frame: Baseline up to Day 29 ]
    VFD 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 [ Time Frame: Day 29 ]
  • Number of Vasopressor Treatment-Free Days [ Time Frame: Baseline up to Day 29 ]
    Vasopressor treatment-free days over 28 days defined as one point for each day during the measurement period that participants are both alive and free of vasopressors.
  • Time to end of Invasive Mechanical Ventilation [ Time Frame: 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.
  • Time to end of Invasive and/or Non-invasive Mechanical Ventilation [ Time Frame: 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.
  • Time to end of Vasopressors Treatment [ Time Frame: 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.
  • Number of Participants With sCABP Clinical Response Visit at Day 14 [ Time Frame: Day 14 ]
    Clinical response: cure,non-response or indeterminate. Cure:complete resolution of pneumonia signs and symptoms present at baseline,no new symptoms or complications attributable to pneumonia.Non-response: failure related or(/) unrelated to pneumonia.Failure related to pneumonia:persistence/progression of baseline signs/symptoms of pneumonia;or baseline radiographic abnormalities after at least 2 days of treatment;or development of new pulmonary or extra pulmonary findings consistent with active infection,or development of new pulmonary infection or extrapulmonary infection requiring antimicrobial therapy;or persistence or progression of baseline signs/symptoms of severe sepsis;or development of new signs or symptoms of severe sepsis;or death due to sepsis.Failure unrelated to pneumonia:any other cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia.Indeterminate assessed if extenuating circumstances preclude classification to one of above.
  • Number of Participants With sCABP Clinical Response Visit at Days 8, 9, 10 and 29 [ Time Frame: Days 8, 9, 10 and 29 ]
    Clinical response: cure,non-response or indeterminate. Cure:complete resolution of pneumonia signs and symptoms present at baseline,no new symptoms or complications attributable to pneumonia.Non-response: failure related or(/) unrelated to pneumonia.Failure related to pneumonia:persistence/progression of baseline signs/symptoms of pneumonia;or baseline radiographic abnormalities after at least 2 days of treatment;or development of new pulmonary or extra pulmonary findings consistent with active infection,or development of new pulmonary infection or extrapulmonary infection requiring antimicrobial therapy;or persistence or progression of baseline signs/symptoms of severe sepsis;or development of new signs or symptoms of severe sepsis;or death due to sepsis.Failure unrelated to pneumonia:any other cause of clinical response failure that in investigator's judgement is unrelated to index pneumonia.Indeterminate assessed if extenuating circumstances preclude classification to one of above.
  • Time to sCABP Clinical Cure [ Time Frame: 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.
  • Duration of Antibiotic Treatment for sCABP [ Time Frame: Baseline up to Day 29 ]
  • Percentage of Participants With Pneumonia Recurrence/ or Reinfection After Clinical Cure [ Time Frame: 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 infiltrate/s or clinically significant worsening of previous ones. If a bacterial pathogen isolated in the recurrent episode is phenotypically different from the one isolated in the previous episode this will be considered as reinfection.
  • Time to Recurrence or Reinfection of Pneumonia After Clinical Cure at sCABP Clinical Response Assessments [ Time Frame: 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 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.
  • 28-day All-Cause Mortality [ Time Frame: Day 28 ]
  • 28-day sCABP-associated Mortality [ Time Frame: Day 28 ]
  • Survival at Days 7, 14, 29, and 90 visits [ Time Frame: Days 7, 14, 29 and 90 ]
  • Time to Death [ Time Frame: Baseline up to Day 90 ]
    Time until participant dies or up to Day 90 post-treatment.
  • Time to Discharge From Intensive Care Unit (ICU) [ Time Frame: Baseline up to Day 29 ]
    Time to discharge from ICU will be defined, in days, as the time between informed consent date and the date of discharge from the ICU.
  • Time to Discharge From Hospital [ Time Frame: Baseline up to Day 29 ]
    Time to discharge from hospital will be defined, in days, as the time between informed consent date and the date of discharge from the hospital.
  • Length of Stay (LOS) in ICU and Hospital After Randomization [ Time Frame: Baseline up to Day 29 ]
    LOS in ICU and hospital after randomization is the sum of all the ICU or hospitalization (resulting from pneumonia) days for a given participant, considering the period from the screening consent date.
  • Number of ICU-free Days [ Time Frame: Baseline up to Day 29 ]
    ICU-free days over 28 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) During Stay at ICU [ Time Frame: Baseline up to Day 29 ]
    The SOFA score will be used to assess the incidence of organ dysfunction or failure in the ICU. The SOFA score ranges from with 0 to 4 points assigned for each of 6 organ dysfunctions: respiration, coagulation, liver, cardiovascular, central nervous system and renal. Higher scores indicate more severe organ failure.
  • Change From Baseline on chest X-ray (CXR) [ Time Frame: Baseline up to Day 29 ]
    Changes on CXR will be assessed at Screening, and then as medically required with at least one CXR per sCABP clinical response assessment until clinical cure from Days 1 to 29 and for pneumonia recurrence/reinfection assessment.
  • Evolution of Partial Pressure of Oxygen /Fraction Inspire Oxygen (PaO2/FiO2) [ 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 hours 0 to 12 post-IMP ]
  • Number Participants Using Rescue Antibiotics [ Time Frame: Baseline up to Day 29 ]
    Use of rescue antibiotics involves addition or change of antibiotic treatments due to the occurrence of antibiotic resistance posterior to microbiology results at baseline or insufficient efficacy during the course of the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • Clinical efficacy of Cx611 in terms of a reduction of the duration of mechanical ventilation and/or vasopressors needed and/or improved survival, and/or clinical cure of the CABP, and other infection-related endpoints. [ Time Frame: 90 days ]
    Explore the clinical efficacy of Cx611 in terms of a reduction of the duration of mechanical ventilation and/or vasopressors needed and/or improved survival, and/or clinical cure of the CABP, and other infection-related endpoints.
  • Understand the mode-of-action of Cx611 in patients with sCABP [ Time Frame: 90 days ]
    Identifying the pro-inflammatory and anti- inflammatory pathways through which Cx611 may affect the underlying processes of sepsis
  • Safety follow-up (SAEs only) [ Time Frame: at 6 and 12 months after Day 1 ]
    SAE collection
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 16, 2017)
Safety Data Collection [ Time Frame: at 18 and 24 months ]
SAE collection via phone call
 
Descriptive Information
Brief Title  ICMJE Cx611-0204 SEPCELL Study
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Bacterial Pneumonia
Intervention  ICMJE
  • Biological: Cx611
    Two intravenous infusions, one on day 1 and another one on day 3.
  • Other: Placebo
    Two intravenous infusions, one on day 1 and another one on day 3.
Study Arms  ICMJE
  • 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
    Intervention: Biological: Cx611
  • 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
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 28, 2020)
84
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2017)
180
Estimated Study Completion Date  ICMJE December 16, 2021
Actual Primary Completion Date July 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  1. Adult subjects of either gender (aged ≥18 years and ≤80 years old.)
  2. Body weight between 50 kg and 100 kg.
  3. Clinical diagnosis of acute (developed within ≤21 past days) community acquired bacterial pneumonia based on the presence of two relevant signs (fever, tachypnoea, leukocytosis, or hypoxemia) and radiographic findings of new pulmonary infiltrate/s.
  4. Subjects with pneumonia of sufficient severity requiring ICU management and with at least one of the two following major criteria of severity present for less than 18 hours:

    1. Requiring invasive mechanical ventilation for respiratory failure due to pneumonia, or
    2. Requiring treatment with vasopressors (i.e., dopamine >5 mcg/kg/min or any dose of epinephrine, norepinephrine, phenylephrine or vasopressin) for at least 2 hours to maintain or attempt to maintain systolic blood pressure (SBP) >90 mm Hg (or mean arterial pressure [MAP] >70 mm Hg) after adequate fluid resuscitation (i.e. for shock).

    NOTE: Patients that are for 18 hours or more under high flow nasal cannula (HFNC) at ≥50 liters per minute and FiO2 ≥0.6 or under non-mechanical ventilation (NMV) are not eligible for the study

  5. Female subject of no childbearing potential i.e. non-fertile, pre-menarche, permanently sterile (i.e. underwent hysterectomy, bilateral salpingectomy or bilateral ovariectomy) or post-menopausal (history of no menses for at least 12 months without an alternative medical cause) or Woman of childbearing potential* with a negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin [hCG]) and agree to use an adequate method of contraception for three months after the last dose of the IMP according to her preferred and usual life style. Adequate methods of female contraception for this study are: sexual abstinence (refraining from heterosexual intercourse), hormonal contraception (both progesterone-only or combined oestrogen and progesterone; both with inhibition of ovulation or where inhibition of ovulation is not the primary mechanism of action), intra-uterine device, bilateral tubal occlusion, condom use by male sexual partner(s) or medically-assessed successfully vasectomized male sexual partner(s).

    *A woman of childbearing potential is a woman between menarche and post-menopause (history of no menses for at least 12 months without an alternative medical cause) unless she has undergone hysterectomy, bilateral salpingectomy or bilateral ovariectomy

    Male subject agreeing to use one of the following methods of birth control according to his preferred and usual life style for three months after the last dose of the IMP: sexual abstinence (refraining from heterosexual intercourse), use of condoms or medically-assessed successful vasectomy , or having a female sexual partner(s) who is using an adequate method of contraception as described above.

  6. Signed informed consent provided by the participant, the relatives or the designated legal representative according to local guidelines.

Exclusion criteria A patient will not be included in the study if he/she meets ANY of the following criteria:

  1. Subjects with Hospital acquired (HAP)-, Health Care acquired (HCAP)- or Ventilator associated-pneumonia (VAP).
  2. Subjects with pneumonia exclusively of viral or fungal origin*. Subjects with bacterial pneumonia co-infected with viruses and/or other microorganisms may be entered into the study.

    *Due to the short time window (up to 18 hours) between fulfillment of severity criteria (i.e. initiation of invasive mechanical ventilation or vasopressors administration, whichever comes first) and the start of the first dose of study treatment, patients with a pneumonia of suspected bacterial origin by any established standard diagnostic method routinely applied at the study site (e.g. urinary antigen test, rt-PCR) can be entered into the study (confirmation of bacterial origin must be obtained afterwards).

  3. Subjects with known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia.
  4. Subjects with an aspiration pneumonia.
  5. Subjects with known active tuberculosis.
  6. Subjects with a history of post-obstructive pneumonia.
  7. Subjects with cystic fibrosis.
  8. Subjects with any chronic lung disease requiring oxygen therapy at home.
  9. Presence of infection in another organ location caused by same pathogen (e.g. pneumococcal meningitis in the context of pneumococcal pneumonia).
  10. Subjects expected to have rapidly fatal disease within 72 hours after randomisation.
  11. Inability to maintain a mean arterial pressure ≥50 mmHg prior to screening despite the presence of vasopressors and intravenous fluids.
  12. Subjects not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases.
  13. Subjects with a history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies.
  14. Subjects with known primary immunodeficiency disorder or with HIV infection and acquired immune deficiency syndrome (AIDS) with CD4 count <200 cells/mm^3 or not receiving highly active antiretroviral therapy (HAART) for HIV.
  15. Subjects receiving immunosuppressant therapy (including chronic treatment with anti-tumour necrosis factor alpha (TNFα ) or on chronic high doses of steroids (single administration of ≥2 mg/kg body weight or 20 mg/day of prednisone or equivalent for ≥2 weeks).
  16. Chronic granulocytopenia, not thought to be due to sepsis, as evidenced by an absolute neutrophil count <500 per µL>21 days prior to onset of pneumonia symptoms.
  17. Subjects who received stem cell therapy, or allogenic transplantation (organ or bone marrow transplant) within the past 6 months.
  18. Subjects receiving treatment with a biological agent (e.g. antibodies, cells), immunotherapy or plasma exchange treatment within the last 8 weeks.
  19. Subjects currently receiving, or having received another investigational medication within 90 days prior to start of the study (or 5 half-lives of the investigational compound, whichever is longer).
  20. Known allergies or hypersensitivity to Penicillin or Streptomycin and/or any component of CryoStor® CS10.
  21. Subjects with a known liver function impairment associated with liver cirrhosis (Child Pugh C) or known oesophageal varices.
  22. Subjects hospitalised within the previous 15 days.
  23. Conditions resulting in a New York Heart Association or Canadian Cardiovascular Society Class IV functional status.
  24. End-stage neuromuscular disorders (e.g. motor neuron diseases, myasthenia gravis, etc.) or cerebral disorders that impair weaning.
  25. Patients with quadriplegia (traumatic or otherwise).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries Belgium,   Italy,   Lithuania,   Norway,   Spain
 
Administrative Information
NCT Number  ICMJE NCT03158727
Other Study ID Numbers  ICMJE Cx611-0204
2015-002994-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Responsible Party Takeda ( Tigenix S.A.U. )
Study Sponsor  ICMJE Tigenix S.A.U.
Collaborators  ICMJE
  • 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  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP