A clinical trial to test the efficacy and safety of a bone marrow cell preparation to treat Critical Limb Ischemia in Subjects with Diabetes Mellitus.
- Conditions
- Critical Limb Ischemia in patients with Diabetes MellitusMedDRA version: 19.1 Level: LLT Classification code 10077142 Term: Limb ischemia System Organ Class: 100000004866MedDRA version: 19.1 Level: LLT Classification code 10058069 Term: Critical limb ischemia System Organ Class: 100000004866MedDRA version: 19.1 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-003980-21-ES
- Lead Sponsor
- Rexgenero Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 78
To be eligible for this trial subjects must satisfy all of the following criteria:
1. Aged = 18 to = 85 years.
2. Diagnosis of Type I or II DM, established more than one year ago.
3. Glycosylated hemoglobin (HbA1c) < 9%.
4. Subjects with poor or no (surgical or endovascular) revascularization option classified as CLI Rutherford Category 5.
For these patients, one of the following must be confirmed and documented at screening:
• Ankle systolic pressure < 70 mmHg, or
• Toe systolic pressure < 50 mmHg, or
• TcpO2 < 30 mmHg (lying down).
Subjects with non-compressible or calcified vessels must qualify on toe pressure or tcpO2.
Poor or no revascularization option means that, in the opinion of the Investigator, revascularization using surgical or endovascular methods are not feasible due to for example the anatomy of existing vessels and/or existing comorbidity and/or previously failed surgical or endovascular revascularization.
5. In the opinion of the Investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance) and pain management is optimized.
6. Women of childbearing potential must have a negative pregnancy test at screening. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Men and women who are sexually active shall use effective contraceptive methods for the duration of their participation in this study if the partner of the male participant, or if the female participant is of childbearing potential. Effective contraceptive methods are e.g.:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal),
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable),
• Intrauterine device (IUD),
• Intrauterine hormone-releasing system (IUS),
• Bilateral tubal occlusion,
• Vasectomised partner, or
• Sexual abstinence.
The use of this contraceptive method should be continued for at least the duration of participation in the study, and should be continued thereafter as long as indicated by the study doctor.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44
Subjects meeting any of the following criteria must not be enrolled in the trial:
1. Advanced CLI defined as presence of major tissue loss as significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads.
2. CLI Rutherford Category 4.
3. Uncontrolled or untreated proliferative retinopathy.
4. Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure.
5. Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger’s Disease), systemic sclerosis (both limited and diffuse forms).
6. Clinical evidence of invasive infection on index leg defined as major tissue loss at the mid-foot or heel involving tendon and/or bone, and/or when intravenous antibiotics are required to treat the infection according to the Investigator.
7. At screening, the presence of only neuropathic ulcers on the index leg.
8. Amputation at or above the talus on the index leg.
9. Planned major amputation within the first month after randomization.
10. On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new, nonstandard-of-care treatments to the index leg during the trial.
11. Blood clotting disorder not caused by medication (e.g., thrombophilia).
12. Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. (34)
13. A platelet count < 50,000/µL.
14. International normalized ratio (INR) > 1.5.
15. Evidence of moderate to severe hepatocellular dysfunction according to the treating physician.
16. Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum.
17. Subjects who may not be healthy enough to successfully complete all protocol requirements including BM collection, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess, as assessed by the Investigator. For example:
a. Concurrent severe congestive heart failure (New York Heart Association Classes III and IV).
b. Life-threatening ventricular arrhythmias, unstable angina (characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration), and/or myocardial infarction within four weeks before screening.
c. Coronary artery bypass grafting or percutaneous coronary intervention within one month before screening.
d. A renal and/or carotid revascularization procedure within one month of screening.
e. Transient ischemic attack within three months prior to screening.
f. Deep vein thrombosis within three months prior to screening.
g. Subjects with immunocompromised con
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: Objective Trial 2<br> The objective of this trial is to confirm the efficacy and safety of an intra-arterial administration of Rexmyelocel-T to treat ischemic ulcers in subjects with DM and CLI Rutherford Category 5.<br> ;Secondary Objective: Not applicable;<br> Primary end point(s): Primary Efficacy Endpoint Trial 2<br><br> Change in Rutherford classification from CLI Category 5 to Category 4 or lower 12 months after administration of Rexmyelocel-T or placebo. Success is defined as complete healing of all ischemic ulcers on the index leg.<br> ;Timepoint(s) of evaluation of this end point: 12 months after administration of Rexmyelocel-T or placebo
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): The following secondary endpoints at 12 months after administration of Rexmyelocel-T or placebo are defined:<br> • Change in Rutherford classification from CLI Category 5 to Category 3 or lower.<br> • Partial healing of ischemic ulcers (> = 50% reduction in size as compared to ulcer size at baseline).<br> • AFS.<br> ;Timepoint(s) of evaluation of this end point: 12 months after administration of Rexmyelocel-T or placebo