Cx611-0204 SEPCELL Study

NCT ID: NCT03158727

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-30
• Study Completion Date: 2020-07-07

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.

Conditions

Bacterial Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Cx611

Intervention Type: BIOLOGICAL

Two intravenous infusions, one on day 1 and another one on day 3.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Two intravenous infusions, one on day 1 and another one on day 3.

Interventions

Cx611

Two intravenous infusions, one on day 1 and another one on day 3.

Intervention Type: BIOLOGICAL

Placebo

Two intravenous infusions, one on day 1 and another one on day 3.

Intervention Type: OTHER

Eligibility Criteria

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

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Centre Hospital Regional Universitaire de Limoges

OTHER

Sponsor Role: collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Hospital San Carlos, Madrid

OTHER

Sponsor Role: collaborator

Tigenix S.A.U.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Clinique Universitaire Saint-Luc

Brussels, Brussels Capital, Belgium

UZ Brussel

Brussels, , Belgium

CHU Sart Tilman

Liège, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

Centre Hospitalier d'Angoulême

Angoulême, , France

Centre Hospitalier Victor Dupouy

Argenteuil, , France

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, , France

CHU Bocage

Dijon, , France

Centre Hospitalier Departemental les Ouidairies

La Roche-sur-Yon, , France

Centre Hospitalier Départemental les Oudairies

La Roche-sur-Yon, , France

Centre Hospitalier Regional Universitaire de Lille

Lille, , France

Centre Hospitalier Universitaire de Limoges - CHU Dupuytren

Limoges, , France

Centre Hospitalier Universitaire de Nantes

Nantes, , France

Centre Hospitalier Regional d'Orleans

Orléans, , France

CHRU de Strasbourg

Strasbourg, , France

CHU TOURS - Hôpital Bretonneau

Tours, , France

Azienda Ospedaliera San'Andrea. UOC Anestesia e Terapia Intensiva

Roma, , Italy

Klaipėda Republican Hospital, The Pulmonology and Allergology Department

Klaipėda, , Lithuania

St. Olavs Hospital, Department of Intensive care Clinical Immunology and Infectious Disease

Trondheim, , Norway

Hospital Universitari Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Mútua de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario de Getafe

Getafe, Madrid, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic I Provincial de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Marqués de Valdecilla

Santander, , Spain

Hospital Universitari de Tarragona Joan XXIII

Tarragona, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Countries

Belgium; France; Italy; Lithuania; Norway; Spain

References

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.

Reference Type: DERIVED

PMID: 37918129 (View on PubMed)

Laterre 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.

Reference Type: DERIVED

PMID: 33238991 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002994-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Cx611-0204

Identifier Type: -

Identifier Source: org_study_id