Randomized, Parallel Group, Placebo Control, Unicentric, Interventional Study to Assess the Effect of Expanded Human Allogeneic Adipose-derived Mesenchymal Adult Stem Cells on the Human Response to Lipopolysaccharyde in Human Volunteers (CELLULA)

Phase I, Randomized, Parallel Group, Placebo Control, Unicentric, Interventional Study to Assess the Effect of Expanded Human Allogeneic Adipose-derived Mesenchymal Adult Stem Cells on the Human Response to Lipopolysaccharyde in Human Volunteers

Phase I, randomized, parallel group, placebo control, unicentric, interventional study. Thirty two healthy male volunteers aged between 18-35 years will be randomized into the eASCs or placebo group if they meet all the inclusion criteria at a 3:1 ratio.

The treatment administration will be infused intravenously to the following groups after randomization:

• First arm: 250,000 cells/kg
• Second arm: 1 million cells/kg
• Third arm: 4 million cells/kg
• Fourth arm: placebo according to their weight.

An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Other: Intravenous infusion of cells

Detailed Description

Medicinal product Suspension of expanded adipose-derived allogeneic adult stem cells (eASCs) at a single dose of 250,000 cells/kg, 1 million cells/kg or 4 million cells/kg by intravenous infusion after suspension in Ringer's lactate solution.

Control Placebo (Ringer's lactate solution) Objectives To investigate the effect of eASCs on the inflammatory response to intravenous LPS in humans.

Design Phase I, randomized, parallel group, placebo control, unicentric, interventional study. Thirty two healthy male volunteers aged between 18-35 years will be randomized into the eASCs or placebo group if they meet all the inclusion criteria at a 3:1 ratio.

The treatment administration will be infused intravenously to the following groups after randomization:

• First arm: 250,000 cells/kg
• Second arm: 1 million cells/kg
• Third arm: 4 million cells/kg
• Fourth arm: placebo according to their weight.

An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. Healthy, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to administration of eASCs (if applicable) and LPS. A subject with a clinical abnormality or laboratory parameter outside the reference range may be included only if the investigator judges that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
2. Male aged between 18 and 35 years, inclusive at the time of signing the informed consent
3. Male subjects (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in activity in which conception is possible while on study medication and for at least 28 days after taking the last dose of study medication
4. Must understand and voluntarily sign an informed consent form prior to the conduct of any study related assessment/procedures. Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:

1. Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavourable for enrolment, including inflammatory diseases
2. Subjects with a history of malignancy
3. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease
4. Subject uses tobacco products
5. Subject has a history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine)
6. History of alcoholism and/or drinking more than 5 units of alcohol per day
7. Any clinically relevant abnormality noted on the 12-lead ECG as judged by the investigator or an average QTc > 450 msec
8. The subject has received an investigational product within three months prior to day 1 of the current study
9. Use of prescription or non-prescription drugs and herbal and dietary supplements within 6 months unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety
10. Transfusion of blood or blood products within 6 months prior to the inclusion in the study.
11. Subject has difficultly in donating blood or accessibility of a vein in left or right arm.
12. Subject has donated more than 350 mL of blood in last 3 months
13. Body mass index >28 kg/m2
14. Presence of a severe bleeding or thrombotic disorder
15. History of known pulmonary embolism or known secondary anti-phospholipid syndrome
16. Subjects known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
17. Known allergies or hypersensitivity to antibiotics, HSA, DMEM, materials of bovine origin, and Ringer's Lactate Solution
18. Any other issue that, in the opinion of the investigator, could be harmful to the subject or compromise interpretation of the data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First arm; 250,000 cells/kg will be administered via intravenous infusion.	Other: Intravenous infusion of cells; The treatment administration will be infused intravenously to the subjects after randomization: An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.
Experimental: Second arm; 1,000,000 cells/kg will be administered via intravenous infusion.	Other: Intravenous infusion of cells; The treatment administration will be infused intravenously to the subjects after randomization: An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.
Experimental: Third arm; 4,000,000 cells/kg will be administered via intravenous infusion.	Other: Intravenous infusion of cells; The treatment administration will be infused intravenously to the subjects after randomization: An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.
Placebo Comparator: Fourth arm; Placebo (Ringer's lactate solution) volume according to subject's weight.	Other: Intravenous infusion of cells; The treatment administration will be infused intravenously to the subjects after randomization: An hour after the end of the eASCs administration, all subjects will be given an intravenous dose of LPS. Subjects will be allowed to leave in the evening once deemed clinically stable by the investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory response as measured by laboratory measurements and functional assays of innate immunology	To investigate the effect of eASCs on the inflammatory response to intravenous LPS in humans.	Change from baseline markers up to 10 hours after LPS injection

Collaborators and Investigators

• Sponsor: Tigenix S.A.U.

Publications and helpful links

General Publications

• Perlee D, van Vught LA, Scicluna BP, Maag A, Lutter R, Kemper EM, van 't Veer C, Punchard MA, Gonzalez J, Richard MP, Dalemans W, Lombardo E, de Vos AF, van der Poll T. Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial. Stem Cells. 2018 Nov;36(11):1778-1788. doi: 10.1002/stem.2891. Epub 2018 Aug 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: April 1, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: Cx611-0102