Cx611-0204 SEPCELL Study

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 180
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TiGenix S.A.U.
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Centre Hospital Regional Universitaire de Limoges; Cliniques universitaires Saint-Luc- Université Catholique de Louvain; European Commission; Hospital San Carlos, Madrid
• Last Updated: 2017-05-16

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:

1. Requiring invasive mechanical ventilation because of the pneumonia, or

2. 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 for three months after the last dose of the investigational medicinal product. 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 for three months after the last dose of the investigational medicinal product, 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.

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-, 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 administration, whichever comes first) and the start 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 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 medical conditions such as end-stage neoplasm or other diseases.

13. Subjects with primary or metastatic lung cancer and patients with anticipated chemotherapy within the next 90 days for any neoplastic syndrome.

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-tumour 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 Penicillin or Streptomycin and/or any component of CryoStor CS10® (please refer to section 9.1.2)

22. Subjects with a known liver function deficiency, e.g. associated with liver cirrhosis (Child PughC) 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).