Critical Limb Ischemia, Peripheral Arterial Disease
Conditions
Brief summary
A Phase I/IIa Dose-Escalation Study Evaluating the Safety, Tolerability and Efficacy of Rejuveinix in Combination With Standard Interventional Therapy for Critical Limb Ischemia Patients with Rutherford Class 4, 5 and 6 Disease
Detailed description
This study is a prospective, randomized, double-blind, multi-center study, comparing MAE and WIQ rates to historical controls to evaluate the safety and efficacy of Rejuveinix for the treatment of patients presenting with symptoms as defined by Rutherford categories 4, 5, or 6, and who have undergone a successful infrainguinal percutaneous intervention within the femoral, femoral-popliteal, popliteal, peroneal, and/or tibial arteries. Treatment at or below the ankle will be permitted (e.g. pedal arteries). This intervention must be successful as defined by ≤ 30% stenosis as determined by angiographic or duplex ultrasound. Preclinical studies support that Rejuveinix has acute perfusion properties that have the potential to provide synergistic benefits to patients after undergoing current standard of care interventional procedures. Following an endovascular intervention, in one or more target vessels/lesions, using FDA cleared technology, such as a bare metal stent, angioplasty, and/or atherectomy, patients will receive Rejuveinix as an adjunct therapy. Enrolled subjects will be assigned randomly to one of two groups. Group A will receive two 20 mL treatments of Rejuveinix per week plus one placebo treatment per week comprised of 20 mL 0.9% saline. A dye will be added to the placebo; the dye will be selected from one found in the Orange Book. Group B will receive three treatments of Rejuveinix per week. Each 20 mL treatments will be combined with 100 mL 0.9% saline and administered via intravenous (IV) injection over the course of a minimum of 30 minutes. The study trial will occur for 12 one-week cycles with a washout period of two days between each cycle (a one-week cycle will include either 2 or 3 Rejuveinix treatments depending on the randomized group). Reven will also assess results calculated on four 21-day cycles to allow for a direct comparison to preclinical results. The goal of the study is to demonstrate Rejuveinix treatment as an adjunctive therapy is non-inferior to historical controls in terms of patient safety, as measured by MAE rates, and efficacy, as assessed by the modified WIQ.
Interventions
DRUGRejuveinix Low Dose
A intravenous administration of Rejuveinix after standard mechanical intervention of blocked peripheral artery
DRUGRejuveinix High Dose
A intravenous administration of Rejuveinix after standard mechanical intervention of blocked peripheral artery
Sponsors
Reven Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
19 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Clinical Inclusion Criteria 1. Subject age \> 18 and \< 90 years of age. 2. Subject has been informed of the nature of the study, agrees to participate and has signed an approved consent form. 3. Subject understands the duration of the study, agrees to follow-up visits and the required testing. 4. Subject has symptomatic lower extremity claudication (meets Rutherford category 4, 5, or 6). 5. Subject has resting ankle-brachial index (ABI) \< 0.5, toe pressure \<50 mmHg, and/or other evidence suggesting severe PAD (ischemic ulceration, for example). Anatomic Inclusion Criteria 1. No more than one-week post revascularization, defined as one of the following: PTA, Stent, or Atherectomy. 2. Stenosis in the femoral, femoral-popliteal, popliteal, peroneal, tibial and/or pedal arteries. 3. Angiographic or duplex ultrasound evidence of significant stenosis ≥ 50% DS of target lesion. 4. Target treatment length from 1 to 25 cm (To include single or multifocal lesions within the target lesion segment. 5. Reference vessel diameter (RVD) ≥ 3.5 mm and ≤ 7 mm. 6. Not expected to require further interventional standard of care treatment during study participation (approximately 174 days). Miscellaneous Inclusion Criteria 1. Anticipated life expectancy \>1 year. 2. Has adequate hepatic function defined as total bilirubin \< 1.5 mg/dL, serum albumin \> 3.0 gm/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 × upper limit of normal (ULN) or \< 5 x ULN for subjects with known hepatic metastases. 3. Has adequate renal function defined as serum creatinine \< 2.5 × ULN. 4. Has adequate bone marrow function defined as a hemoglobin ≥ 10 mg/dL, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L. 5. Must be willing and able to comply with study visits and procedures. 6. Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative urine pregnancy test prior to enrollment in the trial) nor breast-feeding. In addition, a medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP. 7. Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least 30 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative. 8. Subject agrees to refrain from taking multivitamins that include Ascorbic Acid and B-complex vitamins or a Magnesium supplement for a full 24 hours in advance of Week 1, Day 1 through the final Follow-up Visit, Day 174. Clinical
Exclusion criteria
1. Inability to obtain informed consent. 2. Pregnancy or suspected pregnancy during study period. Subjects of childbearing potential must a have negative pregnancy test ≤ 7 days prior to treatment. 3. Recent diagnosis of cancer or treatment for cancer within last 12 months. 4. Life expectancy \< 12 months. 5. CVA \< 1 month prior to screening or any CVA resulting in unresolved walking impairment. 6. STEMI Myocardial infarction \< 1 month prior to procedure. 7. Contraindication to contrast media or any study-required medication. 8. Coagulopathy or clotting disorders. 9. Suspected systemic infection affecting target limb. 10. Serum creatinine ≥ 2.5 mg/dL unless dialysis-dependent. 11. Enrollment in a drug study or medical device investigational research study. 12. Previous standard of care treatment to the same target lesion \< 3 months prior to study enrollment. Anatomic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients with Treatment-related Major Adverse Events as Defined by Re-intervention of the Target Vessel(s), Limb Amputation or Endovascular-related Death. | 84 days | MAE rates compared to an objective performance criterion (historical control). MAEs are defined as re-intervention of the target vessel(s), amputation of all or part of the target limb, or endovascular-related death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Walking Impairment Questionnaire Score Measured at Day 1 and Day 84 in Rejuveinix Treated Patients | 84 days | Walking impairment questionnaire (WIQ), measured at Week 12, Day 84 (-2 to +14 days) compared to baseline assessed Week 1, Day 1 prior to administration of RJX. |
Outcome results
None listed