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: A Pivotal, Placebo-Controlled, Double-Blind, Parallel-Group, Adaptive Trial
- Conditions
- peripheral artery diseaserest pain in legs and feet10047066
- Registration Number
- NL-OMON55357
- Lead Sponsor
- Ixaka Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
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 CLTI Rutherford Category 5.
The blood circulation in these patients must be compromised at screening, 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 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 is not
feasible due to unsuitable anatomy of existing vessels, existing comorbidity
and/or previously failed surgical or endovascular revascularization.
*IMPORTANT: All three measurements must be performed and only one may be used
to meet this criteria
1. Advanced CLTI defined as presence of major tissue loss (i.e significant
ulceration and/or 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.
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 ischemia 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
according to the Investigator intravenous antibiotics are required to treat the
infection.
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. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change in Rutherford classification from CLTI Category 5 to Category 4 or lower<br /><br>12 months after administration of REX-001 or placebo. Success is defined as<br /><br>complete healing of all ischemic ulcers on the index leg.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The following secondary endpoints at 12 months after administration of REX-001<br /><br>or placebo are defined:<br /><br>• Change in Rutherford classification from CLI Category 5 to Category 3 or<br /><br>lower.<br /><br>• Change from Baseline to Visit 9 (12 months) in TcpO2<br /><br>• Partial healing of ischemic ulcers ((>= 50% reduction in size as compared to<br /><br>ulcer size at baseline).<br /><br>• AFS.</p><br>