A clinical trial to test the efficacy and safety of intra-arterial administration of REX-001 to treat ischemic ulcers in subjects with chronic limb threatening ischaemia Rutherford Category 5 and diabetes mellitus.
- Conditions
- Chronic Limb Threatening Ischemia in patients with Diabetes MellitusMedDRA version: 21.1Level: LLTClassification code 10077142Term: Limb ischemiaSystem Organ Class: 100000004866MedDRA version: 24.0Level: LLTClassification code 10058069Term: Critical limb ischemiaSystem Organ Class: 100000004866MedDRA version: 20.0Level: PTClassification code 10012601Term: Diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-003980-21-LV
- Lead Sponsor
- Ixaka Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
1.Aged = 18 to = 85 years.
2.Diagnosis of Type I or II DM, established more than one year ago.
3.Glycosylated haemoglobin (HbA1c) < 9%.
4.Subjects with poor or no (surgical or endovascular) revascularization option classified as CLTI Rutherford Category 5.
The blood circulation in these subjects must be compromised at screening, and can be defined as:
•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, existing comorbidity and/or previously failed surgical or endovascular revascularization.
IMPORTANT: All three pressures measurements must be performed and
only one may be used to meet this criteria
5.In the opinion of the Investigator, the subject is controlled on medical therapy indicated for CLTI (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. Examples of effective contraceptive methods are:
•Combined (oestrogen 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 any contraceptive method should be continued for at least the time the subject participates in the trial, and should be continued thereafter as long as indicated by the Investigator.
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 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
1.Advanced CLTI defined as presence of major tissue loss, i.e., significant ulceration/gangrene proximal to the metatarsal heads (CLTI 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.CLTI Rutherford Category 4.
3.Uncontrolled or untreated proliferative retinopathy (this refers to signs of neovascularization or impaired visual acuity due to retinal oedema for which the patient is not receiving appropriate treatment at the time of enrolment; or if the condition of retinopathy is concluded to be refractory to treatment).
4.Failed surgical or endovascular revascularization on the index leg within 10 days prior to screening
5.Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischaemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger’s Disease), or 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 ischaemic wound-healing within 30 days prior to screening or plans to initiate new treatments (not standard of care) 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 (stage 2 hypertension: Systolic blood pressure = 160 mmHg or diastolic blood pressure = 100 mmHg)(16).
13.A platelet count < 50,000/µL.
14.International normalized ratio (INR) > 1.5. For patients on anticoagulant medication an INR > 1.5 is allowed, provided that the Investigator and the haematologist consider the patient eligible to collect BM.
15.Evidence of moderate to severe hepatocellular dysfunction according to the Investigator . (Subject’s ALT should not exceed >2.5 times that of the normal ALT level)
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 ischaemic attack within three months
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method