Severe community-acquired bacterial pneumonia requiring mechanical ventilation and/or vasopressors.
Conditions
Interventions
Product Name: Allogenic adipose tissue stem adult mesenchymal cells expanded
Product Code: Cx611
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Allogenic adipose tissue stem adult mes
Sponsors
TIGENIX, S.A.U.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects of either sex 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, tachypnea, 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: a) Requiring invasive mechanical ventilation because of the pneumonia, or b) Requiring treatment with vasopressors (i.e., dopamine >5 mg/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. 5. Female subjects who are surgically sterile (e.g. 2-sided tubal resection or ovariectomy) or post-menopausal (history of no menses for at least 24 months) or Women of childbearing potential* must have negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin [hCG]). Sexually active women of childbearing potential must agree to use an adequate method of contraception during the entire duration of the study or for three months after the last dose of the investigational medicinal product, whichever occurs later. An adequate method of contraception is defined as sexual abstinence, adequate hormonal contraception (to have started at least 7 days prior to Screening visit), or an intra-uterine device (to have been in place for at least 2 months prior to Screening visit). *A woman of childbearing potential is sexually mature, has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months(i.e. has had menses at any time in the preceding 24 consecutive months)? or Male subjects agreeing to use condoms during the entire duration of the study or for three months after the last dose of the investigational medicinal product, whichever occurs later, or subjects having a partner who is using a highly efficient method of contraception as described above. 6. Signed informed consent provided by the subject, the relatives or the designated legal representative according to local guidelines. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Subjects with Hospital acquired-, Health Care acquired- or Ventilator associated-pneumonia. 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 fulfilment of severity criteria (i.e. initiation of invasive mechanical ventilation or vasopressors) and administration of the first dose of study treatment, patients with a pneumonia of suspected bacterial origin 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 other infection (i.e. meningitis) caused by same pathogen. 10. Subjects expected to have rapidly fatal disease within 72 hours after randomization. 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 medical conditions such as end-stage neoplasm or other diseases. 13. Subjects with primary or metastatic lung cancer or with anticipated chemotherapy within the next 90 days. 14. Subjects with known primary immunodeficiency disorder or with acquired immune deficiency syndrome (AIDS) with CD4 count < 200 cells/mm3 or not receiving highly active antiretroviral therapy (HAART). 15. Subjects receiving immunosuppressant therapy (including chronic treatment with any anti-tumor necrosis factor alpha (TNFa) 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. Granulocytopenia, not due to sepsis, as evidenced by leukocyte absolute neutrophil count <500 per µL. 17. Haematopoietic and lymphoreticular malignancies, unless in remission. 18. Subjects who received any stem cell, organ or bone marrow transplant within the past 6 months. 19. Subjects with ongoing treatment with a biological agent (e.g. antibodies, cells) or with plasma exchange treatment within the last 8 weeks. 20. 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). 21. Known allergies or hypersensivity to antibiotics and/or any component of CryoStor (please refer to section 9.1.2) 22. Subjects with a known liver function deficiency, e.g. associated with liver cirrhosis (Child Pugh C) or known oesophageal varices. 23. Subjects hospitalised in previous 15 days 24. Conditions resulting in a New York Heart Association Class IV functional status. 25. End-stage neuromuscular disorders that impair weaning (e.g. amyotrophic lateral sclerosis). 26. Patients with complete quadriplegia (traumatic or otherwise).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety endpoints Subjects will be continuously monitored during and after treatment for: ? Frequency, duration, severity, seriousness, relatedness to study treatment, actions taken and outcome of adverse events (AEs), from time of signature of informed consent until end of study (EOS) (Day 90) or study discontinuation. ? Adverse events of specific interest. ? Signs for allergic reactions such as anaphylaxis (changes in systolic and diastolic blood pressures, heart rate, skin reactions and rapid increase of lung resistance due to bronchoconstriction) at Days 1 and 3 (at Pre-dose, and at 0.5, 1, 2, 4, 12 and 24 h after start of infusion). ? Changes in vital signs as follows: Screening, Day 1 (at Pre-dose, and at 0.5, 1, 2, 4, 12 and 24 hr post each dose), Day 2 (at least 4 times), Day 3 (at Pre-dose, and at 0.5, 1, 2, 4, 12 and 24 hr post each dose), then at least 4 times daily while in the ICU or, if discharged from ICU at least once on Days 4, 5, 6, 7, 8-10, 14, 29, 90 or study discontinuation. ? Changes in 12-lead electrocardiogram (ECG) from Screening, Day 1 and Day 3 both Post-dose. ? Changes in haematology and coagulation, clinical chemistry (at least including renal, liver, cholesterol and triglycerides profiles), and urine analysis at Screening, Day 1 Pre-dose, and then at least on Days 2, 3 (only haematology and coagulation), 4, 7, 14, 29, and 90 or study discontinuation. ? Anti-human leukocyte antigen complex (HLA)/donor antibodies (Abs) on Day 1 Pre-dose, Day 14 and Day 90 or study discontinuation.;Main Objective: Investigate the safety profile of 2 allogeneic Cx611 central line infusions within 3 days (on days 1 and 3) at a dose of 160 million cells and to monitor any adverse event and potential immunological host responses against the administered cells during 90 days of follow-up.;Secondary Objective: 1. Explore the clinical efficacy of Cx611 in terms of a reduction of the duration of mechanical ventilation and/or vasopresso | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: See E.5.2;Secondary end point(s): Efficacy endpoints 1. Mechanical ventilator and vasopressors treatment-free days over 28 days. 2. Percentage of patients alive and free of mechanical ventilation and free of vasopressors at Day 29. 3. Percentage of patients alive and free of mechanical ventilation at Day 29. 4. Ventilator free days (VFD) over 28 days. VFD are defined as one point for each day during the measurement period that [subjects] are both alive and free of mechanical ventilation (4). a. E.g., a patient who is extubated on Day 2 of the study and remains alive and free of the ventilator for the remainder of the 28-day study period would receive a VFD score of 26, whereas the patient who is ventilated until death on Day 2 would receive a score of zero. 5. Percentage of patients alive and free of vasopressors at Day 29. 6. Vasopressors-free days over 28 days defined as one point for each day during the measurement period that subjects are both alive and free of vasopressors. 7. Time to end of invasive mechanical ventilation. 8. Time to end of invasive and/or non-invasive mechanical ventilation. 9. Time to end of vasopressors treatment. CABP Clinical Response ? Clinical response visit at Day 14±2 assessed as follows: o Cure: complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. o Non Response: any of the following: - 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/extra pulmonary clinical findings consistent with active infection, or development of new pulmonary infection or extrapulmonary infection requiring antimicrobial therapy other than or in addition to the study product; or persistence/progression of baseline signs/symptoms of severe sepsis; or development of new signs/s | — |
Countries
Belgium, France, Italy, Lithuania, Spain, United Kingdom
Contacts
Public ContactChief Medical Officer
Tigenix
Outcome results
None listed