Critical Limb IschemiaPhase 2CLINCT03994666
Cell Therapy in Critical Limb Ischemia
A Phase 2 study testing allogeneic umbilical cord-derived mesenchymal stem cells in people with Critical Limb Ischemia, run by CHU de Reims at 1 site in France.
Trial summary
Study drug and dosage form : Umbilical cord-derived mesenchymal stem cells (HB-MSC1) Dose and route of administration : 60 × 106 cells or 120 x 106 cells to be injected as 30 individual intramuscular injections, once at V0 within 48 hours to 2 weeks maximum after the revascularization procedure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Limb Ischemia
- What is being tested?
- allogeneic umbilical cord-derived mesenchymal stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2019to Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is suffering from critical limb ischemia due to atheromatous arteriopathy, and defined as existence of chronic pain at rest or trophic disorders, with a systolic pressure inferior to 50 mm Hg at the ankle or inferior to 30 mm Hg at the toe (respectively 70 and 50 mm Hg in case of trophic disorder), or a transcutaneous measure of oxygen pressure (TcPO2) at the back of the foot in decubitus inferior to 30 mm Hg, and is being subject to a revascularization procedure, associated or not to minimally invasive surgery.
- Inclusion confirmation will be performed after the revascularization procedure, and treatment planned within 48 hours to 2 weeks after the revascularization procedure.
- The patient (or his/her legal representative(s)) is capable to understand and comply with study requirements and to provide written informed consent prior to any study procedure for participation in the study and transmission of personal "anonymized" data, which signifies an agreement to enter the study and comply with the restrictions and requirements listed in the informed consent form (ICF).
- Male or female patients aged ≥18 years at the time of signing the ICF.
- A female patient is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) will be required to use one of the treatment methods that does not modify hemostasis parameters (eg chlormadinone acetate [Lutéran]) or must discontinue HRT to allow confirmation of post-menopausal status prior to being enrolled in the study.
- Diabetic patients with an eye fundus examination of less than 3 months excluding proliferative retinopathy
- Patient with a life expectancy >12 months
Who cannot join
- Patients presenting a failure of the revascularization procedure, with technical failure defined as the inability to perform the intended procedure, i.e.
- in the case where femoropopliteal bypass was intended, inability to perform the bypass for any reason
- in the case where endovascular procedure was intended:
- inability to cross the arterial lesion with a guidewire and to catheterize the target vessel
- inability to cross the arterial lesion with any endovascular treatment device such as balloons or stents
- residual stenosis > 50%
Show all 20Show fewer
- Patient with non atheromatous arteriopathy The patient has, or has a history of, any significant disease or disorder that would increase the risk for the patient if they were enrolled in the study or would affect study procedures or outcomes.
- The patient is mentally or legally incapacitated.
- Patient protected by law.
- Patient who does not benefit from the national health insurance coverage.
- The patient has been involved in a previous trial with the investigational product.
- History of cancer excepting basocellular epithelioma during the past 5 years.
- Patient necessitating chronic hemodialysis or creatinine clearance inferior to 30 mL/min.
- History of stroke or myocardial infarction of less than 3 months.
- Hemostasis disorder with contra-indication of intramuscular injections.
- Patients receiving dual antiplatelet therapy that cannot be temporarily discontinued at least 4 days before and until 6 hours after cell implantation.
- Patient receiving an antiplatelet therapy with an adenosine diphosphate receptor inhibitor (ADP/P2Y12 inhibitor) that cannot be temporarily discontinued at least 4 days before and until 6 hours after cell implantation.
- Patient receiving an anticoagulant treatment that cannot be temporarily discontinued until 2 days after the study treatment injection.
- Patients subject to a below the knee femoro-popliteal bypass procedure or to a femoro-tibial bypass procedure
- Patients included in another therapeutic trial
Trial locations and contacts
1 site in 1 country.
France1 site
Damien JOLLY
Reims
Ambroise DUPREY, 03 26 78 46 60 ext. 0033, aduprey@chu-reims.fr
About this study
Official title: Cell Therapy in Critical Limb Ischemia by Implantation of Allogeneic Umbilical Cord-derived Mesenchymal Stem Cells
Study drug and dosage form : Umbilical cord-derived mesenchymal stem cells (HB-MSC1)
Dose and route of administration : 60 × 106 cells or 120 x 106 cells to be injected as 30 individual intramuscular injections, once at V0 within 48 hours to 2 weeks maximum after the revascularization procedure.
Read more
Comparator, dose and route of administration : Placebo, injected as 30 individual intramuscular injections, once at V2 within 48 hours to 2 weeks maximum after the revascularization procedure.
Study centers : 3 centers in France
Study objectives :
Primary: Evaluation of the feasibility and systemic and local tolerance of an implantation, via intramuscular route, of allogenic HB-MSC1, associated with a revascularization procedure, in patients suffering from critical limb ischemia (CLI).
Secondary: Preliminary evaluation of efficacy and dose effect relationship of the MSC implantation in hemodynamic, anatomical and functional terms.
Exploratory: Constitution of a serum bank of the patients included in the study for inflammation and auto immunity biomarkers analysis
Study design : This will be a multicenter Phase IIa study, consisting in a first, open-label, ascending dose feasibility and safety stage followed by a randomized placebo-controlled feasibility, safety and preliminary efficacy stage.
Read the detailed description
Demographics, baseline and follow-up characteristics: descriptive statistics. Primary analysis: Descriptive statistics for the rate of patients with high grade AEs (grade 2 and more), related to the cell implantation will be computed in each arm, with its two-sided 95% CIs.
Each dose arm will be compared to the control arm by computing the absolute difference and the relative risk between the active dose arm and the control arm, together with their 95% two-sided CIs.
The p-values for the comparisons of the difference between the observed absolute rate to 0 and of the relative risk to 1 will be computed, but it is not expected that the study will have sufficient power to detect a significant difference on either of the two statistics (absolute difference or relative risk).
Primary efficacy analysis: The primary efficacy criterion (TcPO2) will be compared between each dose group versus the control group to test for a superiority of MSC over control.
The tested hypotheses are:
- Null hypothesis: mean (MSC dose i) ≤ mean (Control)
- Alternative hypothesis: mean (MSC dose i) > mean (Control) A mixed - model for repeated measures will be used to model the evolution of TcPO2 over time. The significance of the time by treatment interaction will be used to test the two hypotheses. Model adjusted means (LS means) and their differences between treatment arms will be computed at each timepoint.
The LS-Means for change from baseline to 180 days will be used as the primary efficacy endpoint.
Other efficacy analyses: the same analysis model (mixed - model for repeated measures) will be used for all the other continuous efficacy endpoints.
- Conditions
- Critical Limb Ischemia
- Being tested
- allogeneic umbilical cord-derived mesenchymal stem cells, Placebo (NaCl)
- Medical subject headings
- Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allogeneic umbilical cord-derived mesenchymal stem cellsBiological
Injection of mesenchymal stem cells
Placebo (NaCl)Biological
Placebo injection
| Study group | Role | What they receive |
|---|---|---|
| simple dose | Experimental | Not described Receives: Biological: allogeneic umbilical cord-derived mesenchymal stem cells |
| double dose | Experimental | Not described Receives: Biological: allogeneic umbilical cord-derived mesenchymal stem cells |
| placebo | Placebo comparator | Not described Receives: Biological: Placebo (NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment - emergent adverse events
The primary safety endpoint will be the occurrence of any high grade AEs (grade 2 and more), either serious or not, assessed as related to the cell implantation by the investigator, reported over the 360 days of the study period.
AE Intensity Definition :
Grade 1 : asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated ; Grade 2 : minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living ; Grade 3 : severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living ; Grade 4 : life-threatening consequences; urgent intervention indicated ; Grade 5 : death related to adverse event
Measured: Day 1 to day 360
Secondary outcomes (1)
Transcutaneous oxygen pressure
Primary efficacy endpoint: transcutaneous oxygen pressure (TcPO2) mesured in mm Hg
Measured: Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study startSep 2019 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CHU de Reims
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03994666
- Sponsor's protocol ID
- PO19059
- Acronym
- CLI
- Status last verified
- Jun 2019
- First submitted
- 4 Jun 2019
- Last updated
- 21 Jun 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cell Therapy in Critical Limb Ischemia by Implantation of Allogeneic Umbilical Cord-derived Mesenchymal Stem Cells
- ClinicalTrials.gov ID
- NCT03994666
- Acronym / sponsor ID
- CLI / PO19059
- Conditions
- Critical Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- CHU de ReimsUniversity, hospital or other
- Study start
- Sep 2019 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 21 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study drug and dosage form : Umbilical cord-derived mesenchymal stem cells (HB-MSC1)
Dose and route of administration : 60 × 106 cells or 120 x 106 cells to be injected as 30 individual intramuscular injections, once at V0 within 48 hours to 2 weeks maximum after the revascularization procedure.
Comparator, dose and route of administration : Placebo, injected as 30 individual intramuscular injections, once at V2 within 48 hours to 2 weeks maximum after the revascularization procedure.
Study centers : 3 centers in France
Study objectives :
Primary: Evaluation of the feasibility and systemic and local tolerance of an implantation, via intramuscular route, of allogenic HB-MSC1, associated with a revascularization procedure, in patients suffering from critical limb ischemia (CLI).
Secondary: Preliminary evaluation of efficacy and dose effect relationship of the MSC implantation in hemodynamic, anatomical and functional terms.
Exploratory: Constitution of a serum bank of the patients included in the study for inflammation and auto immunity biomarkers analysis
Study design : This will be a multicenter Phase IIa study, consisting in a first, open-label, ascending dose feasibility and safety stage followed by a randomized placebo-controlled feasibility, safety and preliminary efficacy stage.
Detailed description
Demographics, baseline and follow-up characteristics: descriptive statistics. Primary analysis: Descriptive statistics for the rate of patients with high grade AEs (grade 2 and more), related to the cell implantation will be computed in each arm, with its two-sided 95% CIs.
Each dose arm will be compared to the control arm by computing the absolute difference and the relative risk between the active dose arm and the control arm, together with their 95% two-sided CIs.
The p-values for the comparisons of the difference between the observed absolute rate to 0 and of the relative risk to 1 will be computed, but it is not expected that the study will have sufficient power to detect a significant difference on either of the two statistics (absolute difference or relative risk).
Primary efficacy analysis: The primary efficacy criterion (TcPO2) will be compared between each dose group versus the control group to test for a superiority of MSC over control.
The tested hypotheses are:
- Null hypothesis: mean (MSC dose i) ≤ mean (Control)
- Alternative hypothesis: mean (MSC dose i) > mean (Control) A mixed - model for repeated measures will be used to model the evolution of TcPO2 over time. The significance of the time by treatment interaction will be used to test the two hypotheses. Model adjusted means (LS means) and their differences between treatment arms will be computed at each timepoint.
The LS-Means for change from baseline to 180 days will be used as the primary efficacy endpoint.
Other efficacy analyses: the same analysis model (mixed - model for repeated measures) will be used for all the other continuous efficacy endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| simple dose | Experimental | Biological: allogeneic umbilical cord-derived mesenchymal stem cells |
| double dose | Experimental | Biological: allogeneic umbilical cord-derived mesenchymal stem cells |
| placebo | Placebo comparator | Biological: Placebo (NaCl) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The patient is suffering from critical limb ischemia due to atheromatous arteriopathy, and defined as existence of chronic pain at rest or trophic disorders, with a systolic pressure inferior to 50 mm Hg at the ankle or inferior to 30 mm Hg at the toe (respectively 70 and 50 mm Hg in case of trophic disorder), or a transcutaneous measure of oxygen pressure (TcPO2) at the back of the foot in decubitus inferior to 30 mm Hg, and is being subject to a revascularization procedure, associated or not to minimally invasive surgery.
- Inclusion confirmation will be performed after the revascularization procedure, and treatment planned within 48 hours to 2 weeks after the revascularization procedure.
- The patient (or his/her legal representative(s)) is capable to understand and comply with study requirements and to provide written informed consent prior to any study procedure for participation in the study and transmission of personal "anonymized" data, which signifies an agreement to enter the study and comply with the restrictions and requirements listed in the informed consent form (ICF).
- Male or female patients aged ≥18 years at the time of signing the ICF.
- A female patient is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) will be required to use one of the treatment methods that does not modify hemostasis parameters (eg chlormadinone acetate [Lutéran]) or must discontinue HRT to allow confirmation of post-menopausal status prior to being enrolled in the study.
Key exclusion criteria (20 listed)
- Patients presenting a failure of the revascularization procedure, with technical failure defined as the inability to perform the intended procedure, i.e.
- Patient with non atheromatous arteriopathy The patient has, or has a history of, any significant disease or disorder that would increase the risk for the patient if they were enrolled in the study or would affect study procedures or outcomes.
- The patient is mentally or legally incapacitated.
- Patient protected by law.
- Patient who does not benefit from the national health insurance coverage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| allogeneic umbilical cord-derived mesenchymal stem cellsInjection of mesenchymal stem cells | Biological | double dose, simple dose |
| Placebo (NaCl)Placebo injection | Biological | placebo |
Primary outcome
Incidence of treatment - emergent adverse events
Time frame: Day 1 to day 360
The primary safety endpoint will be the occurrence of any high grade AEs (grade 2 and more), either serious or not, assessed as related to the cell implantation by the investigator, reported over the 360 days of the study period. AE Intensity Definition : Grade 1 : asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated ; Grade 2 : minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living ; Grade 3 : severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living ; Grade 4 : life-threatening consequences; urgent intervention indicated ; Grade 5 : death related to adverse event
1 secondary outcome
Transcutaneous oxygen pressure
Time frame: Day 360
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing allogeneic umbilical cord-derived mesenchymal stem cells in people with Critical Limb Ischemia, run by CHU de Reims at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ambroise DUPREY (03 26 78 46 60 ext. 0033, aduprey@chu-reims.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment - emergent adverse events (time frame: Day 1 to day 360). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2019; AzTrials last refreshed its copy on 30 Oct 2026.