Cx611-0204 SEPCELL Study

NCT03158727 | Completed Phase 1 Results DMC

• 2 other identifiers: Cx611-02042015-002994-39
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 33

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.

Conditions

Bacterial Pneumonia

Keywords

Biologic Therapy

Outcome Measures

Primary Outcomes (7)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Baseline up to Day 90

• Number of Participants With Adverse Events of Special Interest (AESI)

  AESIs are predefined adverse events (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.

  Baseline up to Day 90

• Number of Participants With Hypersensitivity Reactions

  Hypersensitivity reactions included 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 hypersensitivity reactions were reported for this outcome measure.

  Baseline up to Day 90

• Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 1

  Day 1

• Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters on Day 3

  Day 3

• Number of Participants With Markedly Abnormal Laboratory Values

  Baseline up to Day 90

• Number of Participants With Anti-human Leukocyte Antigen Complex (Anti-HLA)/Donor Antibodies At Day 1, 14, and 90

  At Days 1, 14, and 90

Secondary Outcomes (27)

• Mechanical Ventilation and Vasopressors Treatment-free Days

  Baseline up to Day 28

• Percentage of Participants Alive and Free of Both Mechanical Ventilation and Vasopressors at Day 29

  Day 29

• Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29

  Day 29

• Number of Ventilator Free Days (VeFD)

  Baseline up to Day 28

• Percentage of Participants Alive and Free of Vasopressors at Day 29

  Day 29

Study Arms (2)

Cx611

EXPERIMENTAL

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.

Biological: Cx611

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Cx611 BIOLOGICAL

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

Cx611

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects of either gender (aged ≥18 years and ≤80 years old.)
• Body weight between 50 kg and 100 kg.
• 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.
• 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:
• Requiring invasive mechanical ventilation for respiratory failure due to pneumonia, or
• 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
• 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.
• Signed informed consent provided by the participant, the relatives or the designated legal representative according to local guidelines.

You may not qualify if:

• Subjects with Hospital acquired (HAP)-, Health Care acquired (HCAP)- or Ventilator associated-pneumonia (VAP).
• 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).
• Subjects with known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia.
• Subjects with an aspiration pneumonia.
• Subjects with known active tuberculosis.
• Subjects with a history of post-obstructive pneumonia.
• Subjects with cystic fibrosis.
• Subjects with any chronic lung disease requiring oxygen therapy at home.
• Presence of infection in another organ location caused by same pathogen (e.g. pneumococcal meningitis in the context of pneumococcal pneumonia).
• Subjects expected to have rapidly fatal disease within 72 hours after randomisation.
• Inability to maintain a mean arterial pressure ≥50 mmHg prior to screening despite the presence of vasopressors and intravenous fluids.
• Subjects not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases.
• Subjects with a history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies.
• 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.

Sponsors & Collaborators

• Tigenix S.A.U.: lead
• European Commission: collaborator
• Centre Hospital Regional Universitaire de Limoges: collaborator
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Hospital San Carlos, Madrid: collaborator

Study Sites (33)

Clinique Universitaire Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

Clinique Saint-Pierre

Ottignies, 1340, Belgium

Location

Centre Hospitalier d'Angoulême

Angoulême, 16959, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, 95107, France

Location

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, 63003, France

Location

CHU Bocage

Dijon, 21000, France

Location

Centre Hospitalier Departemental les Ouidairies

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier Départemental les Oudairies

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier Regional Universitaire de Lille

Lille, 59037, France

Location

Centre Hospitalier Universitaire de Limoges - CHU Dupuytren

Limoges, 87000, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44093, France

Location

Centre Hospitalier Regional d'Orleans

Orléans, 45067, France

Location

CHRU de Strasbourg

Strasbourg, 21000, France

Location

CHU TOURS - Hôpital Bretonneau

Tours, 37000, France

Location

Azienda Ospedaliera San'Andrea. UOC Anestesia e Terapia Intensiva

Roma, 00189, Italy

Location

Klaipėda Republican Hospital, The Pulmonology and Allergology Department

Klaipėda, 92231, Lithuania

Location

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

Trondheim, 7030, Norway

Location

Hospital Universitari Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Mútua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitario de Getafe

Getafe, Madrid, 28905, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitari de Tarragona Joan XXIII

Tarragona, 43005, Spain

Location

Hospital Virgen de la Salud

Toledo, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Related Publications (2)

• 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.

  PMID: 37918129 DERIVED

• 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.

  PMID: 33238991 DERIVED

MeSH Terms

Conditions

Pneumonia, Bacterial

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 18, 2017
• Study Start: January 30, 2017
• Primary Completion: July 7, 2020
• Study Completion: July 7, 2020
• Last Updated: April 6, 2022
• Results First Posted: April 6, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

ES (14); BE (4); NO (1); IT (1); LI (1); FR (12)