Cx611-0204 SEPCELL Study
Cx611-0204 SEPCELL Study
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.
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.
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).